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Xu R, Lin P, Zheng J, Lin Y, Mai Z, Lu Y, Chen X, Zhou Z, Cui L, Zhao X. Orchestrating cancer therapy: Recent advances in nanoplatforms harmonize immunotherapy with multifaceted treatments. Mater Today Bio 2025; 30:101386. [PMID: 39742149 PMCID: PMC11683241 DOI: 10.1016/j.mtbio.2024.101386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 11/17/2024] [Accepted: 12/05/2024] [Indexed: 01/03/2025] Open
Abstract
Advancements in cancer therapy have increasingly focused on leveraging the synergistic effects of combining immunotherapy with other treatment modalities, facilitated by the use of innovative nanoplatforms. These strategies aim to augment the efficacy of standalone treatments while addressing their inherent limitations. Nanoplatforms enable precise delivery and controlled release of therapeutic agents, which enhances treatment specificity and reduces systemic toxicity. This review highlights the critical role of nanomaterials in enhancing immunotherapy when combined with chemotherapy, radiotherapy, photodynamic therapy, photothermal therapy, and sonodynamic therapy. Additionally, it addresses current challenges, including limited in vivo studies, difficulties in standardizing and scaling production, complexities of combination therapies, lack of comparative analyses, and the need for personalized treatments. Future directions involve refining nanoplatform engineering for improved targeting and minimizing adverse effects, alongside large animal studies to establish the long-term efficacy and safety of these combined therapeutic strategies. These efforts aim to translate laboratory successes into clinically viable treatments, significantly improving therapeutic outcomes and advancing the field of oncology.
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Affiliation(s)
- Rongwei Xu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Pei Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Jiarong Zheng
- Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
| | - Yunfan Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Zizhao Mai
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Ye Lu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Xu Chen
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Zihao Zhou
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
| | - Li Cui
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
- School of Dentistry, University of California, Los Angeles, Los Angeles, 90095, CA, USA
| | - Xinyuan Zhao
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, Guangdong, China
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Andrade JFM, Matos BN, Rocho RV, Barbalho GN, Cunha-Filho M, Gelfuso GM, Gratieri T. Evaluation of Dutasteride-Loaded Liposomes and Transfersomes for Follicular-Targeting for Androgenic Alopecia Topical Treatment. Pharmaceutics 2024; 16:1524. [PMID: 39771503 PMCID: PMC11728454 DOI: 10.3390/pharmaceutics16121524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Revised: 11/22/2024] [Accepted: 11/24/2024] [Indexed: 01/16/2025] Open
Abstract
Background/Objectives: Although androgenic alopecia is the most prevalent among non-cicatricial alopecia, it still lacks an effective and safe treatment. Dutasteride (DUT) shows promising results in hair regrowth; however, oral DUT intake causes serious sexual adverse events. Hence, we produced liposomes with different bilayer structures and evaluated the capability of such systems in increasing DUT accumulation in the hair follicles. Methods: In vitro skin penetration tests were performed with porcine ear skin, and the follicular targeting factor (Tf) was calculated as the ratio between DUT amount in HFs and DUT recovered from the sum of all skin layers. Results: While the stiffer DUT-loaded liposome was not able to target the hair follicles in 12 h (Tf = 0.15), a DUT-loaded liposome with an edge activator in its composition, i.e., transfersomes, promoted better control over DUT release and a higher Tf (0.32) (p < 0.005). Conclusions: Transfersomes present higher affinity with DUT providing a better controlled release; hence, they are a better option for DUT follicle targeting compared to liposomes. Further formulation optimizations are needed aiming to prolong such targeting effect.
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Affiliation(s)
| | | | | | | | | | | | - Taís Gratieri
- Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia (UnB), Brasília 70910-900, DF, Brazil; (J.F.M.A.); (B.N.M.); (R.V.R.); (G.N.B.); (M.C.-F.); (G.M.G.)
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Boroughani M, Moaveni AK, Hatami P, Mansoob Abasi N, Seyedoshohadaei SA, Pooladi A, Moradi Y, Rahimi Darehbagh R. Nanocurcumin in cancer treatment: a comprehensive systematic review. Discov Oncol 2024; 15:515. [PMID: 39349709 PMCID: PMC11442806 DOI: 10.1007/s12672-024-01272-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 08/24/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Curcumin, a compound in turmeric, shows potential in cancer treatment but is hindered by low bioavailability and solubility. Nanocurcumin, enhanced through nanotechnology, addresses these limitations, offering potential in oncological applications. This review systematically examines the efficacy, bioavailability, and safety of nanocurcumin in cancer treatment, collating data from in vitro, in vivo, and clinical studies. METHODS A comprehensive systematic search was conducted across four major databases: PubMed (Medline), Scopus, Web of Science, and Embase (up to February 2024). The selection criteria were based on the PICOT structure, and studies were assessed for risk of bias using the Cochrane bias risk tool for clinical studies and related checklists for in vitro and in vivo studies. Statistical analyses were performed in STATA software version 17. RESULTS In total, 8403 articles were identified and assessed, and then only 61 articles were found eligible to be included. Nanocurcumin formulations, especially with Poly (lactic-co-glycolic acid) (PLGA), displayed superior solubility and therapeutic efficacy. In vitro studies highlighted its enhanced cellular uptake and anti-proliferative effects, particularly against cervical cancer cells. In vivo studies confirmed its chemopreventive efficacy and potential synergy with other cancer therapies. Though in early stages, clinical trials showed promise in reducing side effects and improving efficacy in cancer treatments. CONCLUSION Nanocurcumin shows promise as an innovative approach in cancer therapy, potentially offering improved efficacy and reduced side effects compared to traditional treatments. Early clinical trials indicate its potential to enhance the quality of life for cancer patients by mitigating treatment-related toxicities and improving therapeutic outcomes. However, larger randomized controlled trials are necessary to definitively establish its clinical efficacy, optimal dosing regimens, and long-term safety profile across various cancer types. As research progresses, nanocurcumin could become a valuable addition to the oncologist's toolkit, particularly in combination therapies or for patients intolerant to conventional treatments. Future clinical studies should focus on optimizing treatment protocols, identifying responsive patient populations, and assessing long-term outcomes to facilitate the translation of these promising findings into standard clinical practice.
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Affiliation(s)
- Meshkat Boroughani
- Nanoclub Elites Association, Tehran, Iran
- Student Research Committee, Factually of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amir Kian Moaveni
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parsa Hatami
- Student Research Committee, Kurdistan University of Medical Sciences, P.O.Box: 66135-756, Sanandaj, Iran
| | - Neda Mansoob Abasi
- Student Research Committee, Kurdistan University of Medical Sciences, P.O.Box: 66135-756, Sanandaj, Iran
| | - Seyedeh Asrin Seyedoshohadaei
- Department of Psychiatry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Neurosciences Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Arash Pooladi
- Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Medical Genetics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Yousef Moradi
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Ramyar Rahimi Darehbagh
- Student Research Committee, Kurdistan University of Medical Sciences, P.O.Box: 66135-756, Sanandaj, Iran.
- Nanoclub Elites Association, Tehran, Iran.
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
- Universal Scientific Education and Research Network (USERN), Sanandaj, Kurdistan, Iran.
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Nwagwu C, Onugwu A, Echezona A, Uzondu S, Agbo C, Kenechukwu F, Ogbonna J, Ugorji L, Nwobi L, Nwobi O, Mmuotoo O, Ezeibe E, Loretz B, Tarirai C, Mbara KC, Agumah N, Nnamani P, Ofokansi K, Lehr CM, Attama A. Biopolymeric and lipid-based nanotechnological strategies for the design and development of novel mosquito repellent systems: recent advances. NANOSCALE ADVANCES 2024:d4na00474d. [PMID: 39247861 PMCID: PMC11378059 DOI: 10.1039/d4na00474d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 08/15/2024] [Indexed: 09/10/2024]
Abstract
Mosquitoes are the most medically important arthropod vectors of several human diseases. These diseases are known to severely incapacitate and debilitate millions of people, resulting in countless loss of lives. Over the years, several measures have been put in place to control the transmission of mosquito-borne diseases, one of which is using repellents. Repellents are one of the most effective personal protective measures against mosquito-borne diseases. However, conventional delivery systems of repellents (e.g., creams, gels, and sprays) are plagued with toxicity and short-term efficacy issues. The application of biopolymeric and lipid-based systems has been explored over the years to develop better delivery systems for active pharmaceutical ingredients including mosquito repellents. These delivery systems (e.g., solid lipid micro/nanoparticles, micro/nanoemulsions, or liposomes) possess desirable properties such as high biocompatibility, versatility, and controlled/sustained drug delivery, and thus are very important in tackling the clinical challenges of conventional repellent systems. Their capability for controlled/sustained drug release has improved patient compliance as it removes the need for consistent reapplication of repellents. They can also be engineered to reduce repellents' skin permeation, consequently improving their safety. However, despite the benefits that these systems offer very few of them have been successfully translated to the global market for commercial use, a vital challenge that previous reports have not thoroughly examined. The issue of limited clinical translation of novel repellent systems is a vital aspect to consider, as the ultimate goal is to move these systems from bench to bedside. As such, this study seeks to highlight the recent advances in the use of biopolymeric and lipid-based systems for the development of novel mosquito-repellent systems and also analyze the challenges that have limited the clinical translation of these systems while proposing possible strategies to overcome these challenges.
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Affiliation(s)
- Chinekwu Nwagwu
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
- Helmholtz Institute for Pharmaceutical Research Saarland Saarbrucken Germany
| | - Adaeze Onugwu
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Adaeze Echezona
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Samuel Uzondu
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Chinazom Agbo
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Frankline Kenechukwu
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - John Ogbonna
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Lydia Ugorji
- Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria Nsukka Nigeria
| | - Lotanna Nwobi
- Department of Veterinary Physiology and Pharmacology, University of Nigeria Nsukka Nigeria
| | - Obichukwu Nwobi
- Department of Veterinary Public Health and Preventive Medicine, Faculty of Veterinary Medicine, University of Nigeria Nsukka Enugu State Nigeria
| | - Oluchi Mmuotoo
- Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Ezinwanne Ezeibe
- Department of Pharmaceutical Microbiology and Biotechnology, University of Nigeria Nsukka Nigeria
| | - Brigitta Loretz
- Helmholtz Institute for Pharmaceutical Research Saarland Saarbrucken Germany
| | - Clemence Tarirai
- Department of Pharmaceutical Sciences, Faculty of Sciences, Tshwane University of Technology Pretoria South Africa
| | - Kingsley Chimaeze Mbara
- Department of Pharmaceutical Sciences, Faculty of Sciences, Tshwane University of Technology Pretoria South Africa
| | - Nnabuife Agumah
- Department of Applied Microbiology, Faculty of Science, Ebonyi State University Nigeria
| | - Petra Nnamani
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
- Helmholtz Institute for Pharmaceutical Research Saarland Saarbrucken Germany
| | - Kenneth Ofokansi
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
| | - Claus-Micheal Lehr
- Helmholtz Institute for Pharmaceutical Research Saarland Saarbrucken Germany
| | - Anthony Attama
- Drug Delivery and Nanomedicines Research Laboratory, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka Nigeria
- Institute for Drug-Herbal Medicine-Excipient Research and Development, University of Nigeria Nsukka Nigeria
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Sudhakar Patil V, Rupa Bavaskar K, Omprakash Morani D, Suresh Jain A. Review on Hyaluronic Acid Functionalized Sulfur and Nitrogen Co-Doped Graphene Quantum Dots Nano Conjugates for Targeting of Specific Type of Cancer. Adv Pharm Bull 2024; 14:266-277. [PMID: 39206392 PMCID: PMC11347733 DOI: 10.34172/apb.2024.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 03/10/2024] [Accepted: 03/17/2024] [Indexed: 09/04/2024] Open
Abstract
Many people lose their lives to cancer each year. The prevalence of illnesses, metabolic disorders, high-risk infections, and other conditions has been greatly slowed down by expanding scientific research. Chemotherapy and radiation are still the initial lines of treatment for cancer patients, along with surgical removal of tumors. Modifications have been made in chemotherapy since medicines frequently have substantial systemic toxicity and poor pharmacokinetics and still do not reach the tumor site at effective concentrations. Chemotherapy may now be administered more safely and effectively thanks to nanotechnology. Nanotechnology-based graphene quantum dots (GQDs) are very applicable in breast cancer detection, as a drug delivery system, and in the treatment of breast cancer because of their physical and chemical properties, lower toxicity, small size, fluorescence, and effective drug delivery. This paper analyzes the GQDs as cutting-edge platforms for biotechnology and nanomedicine also its application in drug delivery in cancer. It shows that GQDs can be effectively conjugated with hyaluronic acid (HA) to achieve efficient and target-specific delivery.
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Affiliation(s)
- Vinit Sudhakar Patil
- Shri D.D. Vispute College of Pharmacy and Research Center, Devad-Vichumbe, New Panvel, India-410206
| | - Kedar Rupa Bavaskar
- Department of Pharmaceutics, Shri D.D. Vispute College of Pharmacy and Research Center, Devad-Vichumbe, New Panvel, India-410206
| | - Dilip Omprakash Morani
- Department of Pharmaceutics, Bombay Institute of Pharmacy and Research, Dombivali India-421204
| | - Ashish Suresh Jain
- Department of Pharmacognosy, Shri D.D. Vispute College of Pharmacy and Research Center, Devad-Vichumbe, New Panvel, India-410206
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Zhen J, Li X, Yu H, Du B. High-density lipoprotein mimetic nano-therapeutics targeting monocytes and macrophages for improved cardiovascular care: a comprehensive review. J Nanobiotechnology 2024; 22:263. [PMID: 38760755 PMCID: PMC11100215 DOI: 10.1186/s12951-024-02529-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 05/03/2024] [Indexed: 05/19/2024] Open
Abstract
The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.
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Affiliation(s)
- Juan Zhen
- The First Hospital of Jilin University, Changchun, 130021, China
| | - Xiangjun Li
- School of Pharmaceutical Science, Jilin University, Changchun, 130021, China
| | - Haitao Yu
- The First Hospital of Jilin University, Changchun, 130021, China
| | - Bing Du
- The First Hospital of Jilin University, Changchun, 130021, China.
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Ahamad S, Bano N, Khan S, Hussain MK, Bhat SA. Unraveling the Puzzle of Therapeutic Peptides: A Promising Frontier in Huntington's Disease Treatment. J Med Chem 2024; 67:783-815. [PMID: 38207096 DOI: 10.1021/acs.jmedchem.3c01131] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Huntington's disease (HD) is a neurodegenerative genetic disorder characterized by a mutation in the huntingtin (HTT) gene, resulting in the production of a mutant huntingtin protein (mHTT). The accumulation of mHTT leads to the development of toxic aggregates in neurons, causing cell dysfunction and, eventually, cell death. Peptide therapeutics target various aspects of HD pathology, including mHTT reduction and aggregation inhibition, extended CAG mRNA degradation, and modulation of dysregulated signaling pathways, such as BDNF/TrkB signaling. In addition, these peptide therapeutics also target the detrimental interactions of mHTT with InsP3R1, CaM, or Caspase-6 proteins to mitigate HD. This Perspective provides a detailed perspective on anti-HD therapeutic peptides, highlighting their design, structural characteristics, neuroprotective effects, and specific mechanisms of action. Peptide therapeutics for HD exhibit promise in preclinical models, but further investigation is required to confirm their effectiveness as viable therapeutic strategies, recognizing that no approved peptide therapy for HD currently exists.
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Affiliation(s)
- Shakir Ahamad
- Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India
| | - Nargis Bano
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Sameera Khan
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | | | - Shahnawaz A Bhat
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
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Yang M, Chen Y, Zhu L, You L, Tong H, Meng H, Sheng J, Jin J. Harnessing Nanotechnology: Emerging Strategies for Multiple Myeloma Therapy. Biomolecules 2024; 14:83. [PMID: 38254683 PMCID: PMC10813273 DOI: 10.3390/biom14010083] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/02/2024] [Accepted: 01/03/2024] [Indexed: 01/24/2024] Open
Abstract
Advances in nanotechnology have provided novel avenues for the diagnosis and treatment of multiple myeloma (MM), a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. This review elucidates the potential of nanotechnology to revolutionize myeloma therapy, focusing on nanoparticle-based drug delivery systems, nanoscale imaging techniques, and nano-immunotherapy. Nanoparticle-based drug delivery systems offer enhanced drug targeting, reduced systemic toxicity, and improved therapeutic efficacy. We discuss the latest developments in nanocarriers, such as liposomes, polymeric nanoparticles, and inorganic nanoparticles, used for the delivery of chemotherapeutic agents, siRNA, and miRNA in MM treatment. We delve into nanoscale imaging techniques which provide spatial multi-omic data, offering a holistic view of the tumor microenvironment. This spatial resolution can help decipher the complex interplay between cancer cells and their surrounding environment, facilitating the development of highly targeted therapies. Lastly, we explore the burgeoning field of nano-immunotherapy, which employs nanoparticles to modulate the immune system for myeloma treatment. Specifically, we consider how nanoparticles can be used to deliver tumor antigens to antigen-presenting cells, thus enhancing the body's immune response against myeloma cells. In conclusion, nanotechnology holds great promise for improving the prognosis and quality of life of MM patients. However, several challenges remain, including the need for further preclinical and clinical trials to assess the safety and efficacy of these emerging strategies. Future research should also focus on developing personalized nanomedicine approaches, which could tailor treatments to individual patients based on their genetic and molecular profiles.
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Affiliation(s)
- Min Yang
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Yu Chen
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Li Zhu
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Liangshun You
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Hongyan Tong
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Haitao Meng
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Jianpeng Sheng
- Zhejiang University Cancer Center, Hangzhou 310029, China;
| | - Jie Jin
- Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; (M.Y.); (Y.C.); (L.Z.); (L.Y.); (H.T.); (H.M.)
- Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou 310027, China
- Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou 310003, China
- Zhejiang University Cancer Center, Hangzhou 310029, China;
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Verma S, Malviya R, Srivastava S, Ahmad I, Singh B, Almontasheri R, Uniyal P. Shape Dependent Therapeutic Potential of Nanoparticulate System: Advance Approach for Drug Delivery. Curr Pharm Des 2024; 30:2606-2618. [PMID: 39034725 DOI: 10.2174/0113816128314618240628110218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 06/09/2024] [Accepted: 06/11/2024] [Indexed: 07/23/2024]
Abstract
Drug delivery systems rely heavily on nanoparticles because they provide a targeted and monitored release of pharmaceuticals that maximize therapeutic efficacy and minimize side effects. To maximize drug internalization, this review focuses on comprehending the interactions between biological systems and nanoparticles. The way that nanoparticles behave during cellular uptake, distribution, and retention in the body is determined by their shape. Different forms, such as mesoporous silica nanoparticles, micelles, and nanorods, each have special properties that influence how well drugs are delivered to cells and internalized. To achieve the desired particle morphology, shape-controlled nanoparticle synthesis strategies take into account variables like pH, temperatures, and reaction time. Top-down techniques entail dissolving bulk materials to produce nanoparticles, whereas bottom-up techniques enable nanostructures to self-assemble. Comprehending the interactions at the bio-nano interface is essential to surmounting biological barriers and enhancing the therapeutic efficacy of nanotechnology in drug delivery systems. In general, drug internalization and distribution are greatly influenced by the shape of nanoparticles, which presents an opportunity for tailored and efficient treatment plans in a range of medical applications.
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Affiliation(s)
- Shristy Verma
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Saurabh Srivastava
- School of Pharmacy, KPJ Healthcare University College (KPJUC), Nilai 71800, Malaysia
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | | | - Rasha Almontasheri
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Prerna Uniyal
- School of Pharmacy, Graphic Era Hill University, Dehradun, India
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Hirulkar R, Chaurawal N, Alhodieb FS, Barkat H, Preet S, Raza K. Nanotheranostics: Clinical Status, Toxicity, Regulatory Consideration, and Future Prospects. NANOTHERANOSTICS FOR DIAGNOSIS AND THERAPY 2024:249-285. [DOI: 10.1007/978-981-97-3115-2_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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11
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Garg A, Agrawal R, Chopra H, Singh T, Chaudhary R, Tankara A. A Glance on Nanovaccine: A Potential Approach for Disease Prevention. Curr Pharm Biotechnol 2024; 25:1406-1418. [PMID: 37861010 DOI: 10.2174/0113892010254221231006100659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 08/03/2023] [Accepted: 08/18/2023] [Indexed: 10/21/2023]
Abstract
There are several vaccines available for preventing various bacterial and viral infections, but still, there are many challenges that require the development of noninvasive, more efficient, and active vaccines. The advancement in biotechnological tools has provided safer antigens, such as nucleic acids, proteins etc., but due to their lower immunogenic property, adjuvants of stronger immune response are required. Nanovaccines are effective vaccines when compared with conventional vaccines as they can induce both Humoral and cell-mediated immune responses and also provide longer immunogenic memory. The nanocarriers used in vaccines act as adjuvant. They provide site-specific delivery of antigens and can be used in conjugation with immunostimulatory molecules for enhancing adjuvant therapy. The nanovaccines avoid degrading cell pathways and provide effective absorption into blood vessels. The higher potential of nanovaccines to treat various diseases, such as acquired immuno deficiency syndrome, cancer, tuberculosis, malaria and many others, along with their immunological mechanisms and different types, have been discussed in the review.
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Affiliation(s)
- Akash Garg
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Rutvi Agrawal
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Himansu Chopra
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Talever Singh
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Ramkumar Chaudhary
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Abhishek Tankara
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
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12
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Sterle Zorec B. Two-dimensional printing of nanoparticles as a promising therapeutic method for personalized drug administration. Pharm Dev Technol 2023; 28:826-842. [PMID: 37788221 DOI: 10.1080/10837450.2023.2264920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 09/26/2023] [Indexed: 10/05/2023]
Abstract
The necessity for personalized patient treatment has drastically increased since the contribution of genes to the differences in physiological and metabolic state of individuals have been exposed. Different approaches have been considered so far in order to satisfy all of the diversities in patient needs, yet none of them have been fully implemented thus far. In this framework, various types of 2D printing technologies have been identified to offer some potential solutions for personalized medication, which development is increasing rapidly. Accurate drug-on-demand deposition, the possibility of consuming multiple drug substances in one product and adjusting individual drug concentration are just some of the few benefits over existing bulk pharmaceuticals manufacture, which printing technologies brings. With inclusion of nanotechnology by printing nanoparticles from its dispersions some further opportunities such as controlled and stimuli-responsive drug release or targeted and dose depending on drug delivery were highlighted. Yet, there are still some challenges to be solved before such products can reach the pharmaceutical market. In those terms mostly chemical, physical as well as microbiological stability concerns should be answered, with which 2D printing technology could meet the treatment needs of every individual and fulfill some existing drawbacks of large-scale batch production of pharmaceuticals we possess today.
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Affiliation(s)
- Barbara Sterle Zorec
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
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13
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Gupta P, Neupane YR, Aqil M, Kohli K, Sultana Y. Lipid-based nanoparticle-mediated combination therapy for breast cancer management: a comprehensive review. Drug Deliv Transl Res 2023; 13:2739-2766. [PMID: 37261602 DOI: 10.1007/s13346-023-01366-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2023] [Indexed: 06/02/2023]
Abstract
Breast cancer due to the unpredictable and complex etiopathology combined with the non-availability of any effective drug treatment has become the major root of concern for oncologists globally. The number of women affected by the said disease state is increasing at an alarming rate attributed to environmental and lifestyle changes indicating at the exploration of a novel treatment strategy that can eradicate this aggressive disease. So far, it is treated by promising nanomedicine monotherapy; however, according to the numerous studies conducted, the inadequacy of these nano monotherapies in terms of elevated toxicity and resistance has been reported. This review, therefore, puts forth a new multimodal strategic approach to lipid-based nanoparticle-mediated combination drug delivery in breast cancer, emphasizing the recent advancements. A basic overview about the combination therapy and its index is firstly given. Then, the various nano-based combinations of chemotherapeutics involving the combination delivery of synthetic and herbal agents are discussed along with their examples. Further, the recent exploration of chemotherapeutics co-delivery with small interfering RNA (siRNA) agents has also been explained herein. Finally, a section providing a brief description of the delivery of chemotherapeutic agents with monoclonal antibodies (mAbs) has been presented. From this review, we aim to provide the researchers with deep insight into the novel and much more effective combinational lipid-based nanoparticle-mediated nanomedicines tailored specifically for breast cancer treatment resulting in synergism, enhanced antitumor efficacy, and low toxic effects, subsequently overcoming the hurdles associated with conventional chemotherapy.
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Affiliation(s)
- Priya Gupta
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
| | - Yub Raj Neupane
- Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, 52242, USA
| | - Mohd Aqil
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
| | - Kanchan Kohli
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.
- Lloyd Institute of Management & Technology (Pharm.), Plot No. 11, Knowledge Park-II, Greater Noida, Uttar Pradesh, 201308, India.
| | - Yasmin Sultana
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.
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Zhao DK, Liang J, Huang XY, Shen S, Wang J. Organoids technology for advancing the clinical translation of cancer nanomedicine. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2023; 15:e1892. [PMID: 37088100 DOI: 10.1002/wnan.1892] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/13/2023] [Accepted: 02/15/2023] [Indexed: 04/25/2023]
Abstract
The past decades have witnessed the rapid development and widespread application of nanomedicines in cancer treatment; however, the clinical translation of experimental findings has been low, as evidenced by the low percentage of commercialized nanomedicines. Incomplete understanding of nanomedicine-tumor interactions and inappropriate evaluation models are two important challenges limiting the clinical translation of cancer nanomedicines. Currently, nanomedicine-tumor interaction and therapeutic effects are mainly investigated using cell lines or mouse models, which do not recapitulate the complex tumor microenvironment in human patients. Thus, information obtained from cell lines and mouse models cannot provide adequate guidance for the rational redesign of nanomedicine. Compared with other preclinical models, tumor organoids constructed from patient-derived tumor tissues are superior in retaining the key histopathological, genetic, and phenotypic features of the parent tumor. We speculate that organoid technology would help elucidate nanomedicine-tumor interaction in the tumor microenvironment and guide the design of nanomedicine, making it a reliable tool to accurately predict drug responses in patients with cancer. This review highlighted the advantages of drug delivery systems in cancer treatment, challenges limiting the clinical translation of antitumor nanomedicines, and potential application of patient-derived organoids (PDO) in nanomedicine. We propose that combining organoids and nanotechnology would facilitate the development of safe and effective cancer nanomedicines and accelerate their clinical application. This review discussed the potential translational value of integrative research using organoids and cancer nanomedicine. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Affiliation(s)
- Dong-Kun Zhao
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
| | - Jie Liang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
- Shenzhen Bay Laboratory, Shenzhen, China
| | - Xiao-Yi Huang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China
| | - Song Shen
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
- National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China
| | - Jun Wang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China
- Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, China
- Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, China
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Kommineni N, Chaudhari R, Conde J, Tamburaci S, Cecen B, Chandra P, Prasad R. Engineered Liposomes in Interventional Theranostics of Solid Tumors. ACS Biomater Sci Eng 2023; 9:4527-4557. [PMID: 37450683 DOI: 10.1021/acsbiomaterials.3c00510] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
Engineered liposomal nanoparticles have unique characteristics as cargo carriers in cancer care and therapeutics. Liposomal theranostics have shown significant progress in preclinical and clinical cancer models in the past few years. Liposomal hybrid systems have not only been approved by the FDA but have also reached the market level. Nanosized liposomes are clinically proven systems for delivering multiple therapeutic as well as imaging agents to the target sites in (i) cancer theranostics of solid tumors, (ii) image-guided therapeutics, and (iii) combination therapeutic applications. The choice of diagnostics and therapeutics can intervene in the theranostics property of the engineered system. However, integrating imaging and therapeutics probes within lipid self-assembly "liposome" may compromise their overall theranostics performance. On the other hand, liposomal systems suffer from their fragile nature, site-selective tumor targeting, specific biodistribution and premature leakage of loaded cargo molecules before reaching the target site. Various engineering approaches, viz., grafting, conjugation, encapsulations, etc., have been investigated to overcome the aforementioned issues. It has been studied that surface-engineered liposomes demonstrate better tumor selectivity and improved therapeutic activity and retention in cells/or solid tumors. It should be noted that several other parameters like reproducibility, stability, smooth circulation, toxicity of vital organs, patient compliance, etc. must be addressed before using liposomal theranostics agents in solid tumors or clinical models. Herein, we have reviewed the importance and challenges of liposomal medicines in targeted cancer theranostics with their preclinical and clinical progress and a translational overview.
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Affiliation(s)
- Nagavendra Kommineni
- Center for Biomedical Research, Population Council, New York, New York 10065, United States
| | - Ruchita Chaudhari
- School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - João Conde
- ToxOmics, NOVA Medical School, Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa; Lisboa 1169-056, Portugal
| | - Sedef Tamburaci
- Department of Chemical Engineering, Izmir Institute of Technology, Gulbahce Campus, Izmir 35430, Turkey
| | - Berivan Cecen
- Department of Biomedical Engineering, Rowan University, Glassboro, New Jersey 08028, United States
- Department of Mechanical Engineering, Rowan University, Glassboro, New Jersey 08028, United States
| | - Pranjal Chandra
- School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi 221005, India
| | - Rajendra Prasad
- School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi 221005, India
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16
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Talarico L, Pepi S, Susino S, Leone G, Bonechi C, Consumi M, Clemente I, Magnani A. Design and Optimization of Solid Lipid Nanoparticles Loaded with Triamcinolone Acetonide. Molecules 2023; 28:5747. [PMID: 37570717 PMCID: PMC10420805 DOI: 10.3390/molecules28155747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/25/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
Principles of quality by design and design of experiments are acquiring more importance in the discovery and application of new drug carriers, such as solid lipid nanoparticles. In this work, an optimized synthesis of solid lipid nanoparticles loaded with Triamcinolone Acetonide is presented using an approach that involves Stearic Acid as a lipid, soy PC as an ionic surfactant, and Tween 80 as a nonionic surfactant. The constructed circumscribed Central Composite Design considers the lipid and nonionic surfactant quantities and the sonication amplitude in order to optimize particle size and Zeta potential, both measured by means of Dynamic Light Scattering, while the separation of unentrapped drug from the optimized Triamcinolone Acetonide-loaded solid lipid nanoparticles formulation is performed by Size Exclusion Chromatography and, subsequently, the encapsulation efficiency is determined by HPLC-DAD. The proposed optimized formulation-with the goal of maximizing Zeta potential and minimizing particle size-has shown good accordance with predicted values of Zeta potential and dimensions, as well as a high value of encapsulated Triamcinolone Acetonide. Experimental values obtained from the optimized synthesis reports a dimension of 683 ± 5 nm, which differs by 3% from the predicted value, and a Zeta potential of -38.0 ± 7.6 mV (12% difference from the predicted value).
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Affiliation(s)
- Luigi Talarico
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM)—Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
| | - Simone Pepi
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM)—Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
| | - Surama Susino
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
| | - Gemma Leone
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM)—Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
| | - Claudia Bonechi
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM)—Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
| | - Marco Consumi
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM)—Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
| | - Ilaria Clemente
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
| | - Agnese Magnani
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy; (S.P.); (S.S.); (G.L.); (C.B.); (M.C.); (I.C.)
- National Interuniversity Consortium of Materials Science and Technology (INSTM)—Siena Research Unit, Via G. Giusti 9, 50121 Firenze, Italy
- Siena Research Group—Center for Colloids and Surface Science (CSGI), University of Florence, Via della Lastruccia 3, 50019 Firenze, Italy
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Guinart A, Korpidou M, Doellerer D, Pacella G, Stuart MCA, Dinu IA, Portale G, Palivan C, Feringa BL. Synthetic molecular motor activates drug delivery from polymersomes. Proc Natl Acad Sci U S A 2023; 120:e2301279120. [PMID: 37364098 PMCID: PMC10319042 DOI: 10.1073/pnas.2301279120] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 04/27/2023] [Indexed: 06/28/2023] Open
Abstract
The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS-b-PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.
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Affiliation(s)
- Ainoa Guinart
- Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, 9747 AGGroningen, The Netherlands
| | - Maria Korpidou
- Department of Chemistry, University of Basel, BPR 1096, 4058Basel, Switzerland
| | - Daniel Doellerer
- Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, 9747 AGGroningen, The Netherlands
| | - Gianni Pacella
- Faculty of Science and Engineering, Zernike Institute for Advanced Materials, University of Groningen, 9747 AGGroningen, The Netherlands
| | - Marc C. A. Stuart
- Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, 9747 AGGroningen, The Netherlands
| | - Ionel Adrian Dinu
- Department of Chemistry, University of Basel, BPR 1096, 4058Basel, Switzerland
- National Centre of Competence in Research-Molecular Systems Engineering, BioPark Rosental 1095Basel, Switzerland
| | - Giuseppe Portale
- Faculty of Science and Engineering, Zernike Institute for Advanced Materials, University of Groningen, 9747 AGGroningen, The Netherlands
| | - Cornelia Palivan
- Department of Chemistry, University of Basel, BPR 1096, 4058Basel, Switzerland
- National Centre of Competence in Research-Molecular Systems Engineering, BioPark Rosental 1095Basel, Switzerland
- Swiss Nanoscience Institute, University of Basel, 4056Basel, Switzerland
| | - Ben L. Feringa
- Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, 9747 AGGroningen, The Netherlands
- Faculty of Science and Engineering, Zernike Institute for Advanced Materials, University of Groningen, 9747 AGGroningen, The Netherlands
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Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Cairo-11884, Egypt, A. Askar A, M. Abouzaid A, Dubey A, El-Zahaby SA. MEGAMOX MEDIATES ECO-FRIENDLY SYNTHESIS OF SELENIUM NANOPARTICLES AS IMMUNOMODULATORY, ANTIOXIDANT AND ANTIMICROBIAL AGENTS. INDIAN DRUGS 2022; 59:80-90. [DOI: 10.53879/id.59.10.12817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/02/2024]
Abstract
The research herein includes methodology for eco-friendly preparation of selenium nanoparticles (SeNPs) using the broad-spectrum antibiotic, Megamox (Mega.). Characterization of SeNPs was done using UV-Visible spectroscopy, FTIR, XRD, DLS and TEM imaging. Additionally, the immunomodulatory, antioxidant and antimicrobial activities of both SeNPs and Mega. were checked against different strains of bacteria and fungi. TEM and DLS images showed that SeNPs are polydisperse spheres with mean diameter of 22.4 nm. FTIR analysis indicated that the hydroxyl and nitrogen moieties in Mega. were effective for reduction plus binding manner. According to the results of the nitro blue tetrazolium reduction test, both SeNPs and Mega. presented high intracellular killing activity, which confirmed their immunostimulatory effect. Antioxidant activity of SeNPs and Mega. were 90 and 82 %, respectively. SeNPs presented great activity facing multi-drug resistant bacteria and TB. SeNPs are considered promising cost-effective and eco-friendly anti-bacterial and anti-fungal agents that can represent a new potential nano-platform in both medical and infectious diseases control.
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19
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Nanotechnology in the Diagnosis and Treatment of Osteomyelitis. Pharmaceutics 2022; 14:pharmaceutics14081563. [PMID: 36015188 PMCID: PMC9412360 DOI: 10.3390/pharmaceutics14081563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/15/2022] [Accepted: 07/18/2022] [Indexed: 11/23/2022] Open
Abstract
Infection remains one of the largest threats to global health. Among those infections that are especially troublesome, osteomyelitis, or inflammation of the bone, typically due to infection, is a particularly difficult condition to diagnose and treat. This difficulty stems not only from the biological complexities of opportunistic infections designed to avoid the onslaught of both the host immune system as well as exogenous antibiotics, but also from changes in the host vasculature and the heterogeneity of infectious presentations. While several groups have attempted to classify and stage osteomyelitis, controversy remains, often delaying diagnosis and treatment. Despite a host of preclinical treatment advances being incubated in academic and company research and development labs worldwide, clinical treatment strategies remain relatively stagnant, including surgical debridement and lengthy courses of intravenous antibiotics, both of which may compromise the overall health of the bone and the patient. This manuscript reviews the current methods for diagnosing and treating osteomyelitis and then contemplates the role that nanotechnology might play in the advancement of osteomyelitis treatment.
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Patel NC, Patel HA. A recent solidification approach for nanosuspension: formulation, optimisation and evaluation of canagliflozin immediate release pellets. Folia Med (Plovdiv) 2022; 64:488-500. [PMID: 35856111 DOI: 10.3897/folmed.64.e68866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 08/02/2021] [Indexed: 11/12/2022] Open
Abstract
Abstract.
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Lee E, Lee M, Kwon S, Kim J, Kwon Y. Systematic and mechanistic analysis of AuNP-induced nanotoxicity for risk assessment of nanomedicine. NANO CONVERGENCE 2022; 9:27. [PMID: 35680772 PMCID: PMC9184696 DOI: 10.1186/s40580-022-00320-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/29/2022] [Indexed: 05/02/2023]
Abstract
For decades, nanoparticles (NPs) have been widely implemented in various biomedical fields due to their unique optical, thermal, and tunable properties. Particularly, gold nanoparticles (AuNPs) have opened new frontiers in sensing, targeted drug delivery, imaging, and photodynamic therapy, showing promising results for the treatment of various intractable diseases that affect quality of life and longevity. Despite the tremendous achievements of AuNPs-based approaches in biomedical applications, few AuNP-based nanomedicines have been evaluated in clinical trials, which is likely due to a shortage of understanding of the biological and pathological effects of AuNPs. The biological fate of AuNPs is tightly related to a variety of physicochemical parameters including size, shape, chemical structure of ligands, charge, and protein corona, and therefore evaluating the effects of these parameters on specific biological interactions is a major ongoing challenge. Therefore, this review focuses on ongoing nanotoxicology studies that aim to characterize the effect of various AuNP characteristics on AuNP-induced toxicity. Specifically, we focus on understanding how each parameter alters the specific biological interactions of AuNPs via mechanistic analysis of nano-bio interactions. We also discuss different cellular functions affected by AuNP treatment (e.g., cell motility, ROS generation, interaction with DNA, and immune response) to understand their potential human health risks. The information discussed herein could contribute to the safe usage of nanomedicine by providing a basis for appropriate risk assessment and for the development of nano-QSAR models.
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Affiliation(s)
- Euiyeon Lee
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
- Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, 08854, USA
| | - Minhyeong Lee
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - San Kwon
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - Jongpil Kim
- Department of Chemistry, Dongguk University, Seoul, 04620, Korea.
| | - Youngeun Kwon
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea.
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Đorđević S, Gonzalez MM, Conejos-Sánchez I, Carreira B, Pozzi S, Acúrcio RC, Satchi-Fainaro R, Florindo HF, Vicent MJ. Current hurdles to the translation of nanomedicines from bench to the clinic. Drug Deliv Transl Res 2022; 12:500-525. [PMID: 34302274 PMCID: PMC8300981 DOI: 10.1007/s13346-021-01024-2] [Citation(s) in RCA: 146] [Impact Index Per Article: 48.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2021] [Indexed: 02/07/2023]
Abstract
The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines.
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Affiliation(s)
- Snežana Đorđević
- Polymer Therapeutics Laboratory, Prince Felipe Research Center (CIPF), Eduardo Primo Yúfera 3, 46012, Valencia, Av, Spain
| | - María Medel Gonzalez
- Polymer Therapeutics Laboratory, Prince Felipe Research Center (CIPF), Eduardo Primo Yúfera 3, 46012, Valencia, Av, Spain
| | - Inmaculada Conejos-Sánchez
- Polymer Therapeutics Laboratory, Prince Felipe Research Center (CIPF), Eduardo Primo Yúfera 3, 46012, Valencia, Av, Spain
| | - Barbara Carreira
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal
| | - Sabina Pozzi
- Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel
| | - Rita C Acúrcio
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal
| | - Ronit Satchi-Fainaro
- Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.
- Sagol School of Neuroscience, Tel Aviv University, 69978, Tel Aviv, Israel.
| | - Helena F Florindo
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal.
| | - María J Vicent
- Polymer Therapeutics Laboratory, Prince Felipe Research Center (CIPF), Eduardo Primo Yúfera 3, 46012, Valencia, Av, Spain.
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23
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De Silva L, Fu JY, Htar TT, Wan Kamal WHB, Kasbollah A, Muniyandy S, Chuah LH. Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging. Front Pharmacol 2022; 12:778396. [PMID: 35069200 PMCID: PMC8777053 DOI: 10.3389/fphar.2021.778396] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/10/2021] [Indexed: 11/13/2022] Open
Abstract
The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.
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Affiliation(s)
- Leanne De Silva
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Ju-Yen Fu
- Nutrition Unit, Malaysian Palm Oil Board, Bandar Baru Bangi, Malaysia
| | - Thet Thet Htar
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
| | | | - Azahari Kasbollah
- Medical Technology Division, Malaysian Nuclear Agency, Bangi, Malaysia
| | - Saravanan Muniyandy
- Department of Pharmacy, Fatima College of Health Sciences, Al Ain, United Arab Emirates
| | - Lay-Hong Chuah
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
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24
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Ranjha MMAN, Shafique B, Rehman A, Mehmood A, Ali A, Zahra SM, Roobab U, Singh A, Ibrahim SA, Siddiqui SA. Biocompatible Nanomaterials in Food Science, Technology, and Nutrient Drug Delivery: Recent Developments and Applications. Front Nutr 2022; 8:778155. [PMID: 35127783 PMCID: PMC8811221 DOI: 10.3389/fnut.2021.778155] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/29/2021] [Indexed: 12/17/2022] Open
Abstract
Nanomaterials exist as potential biocompatible materials in nature and are being synthesized to provide extraordinary characteristics in various food industry sectors. Synthesis of biocompatible nanomaterials requires modification in the shape, density, and size of nanomaterials. Biocompatible nanomaterials are synthesized to reduce toxicity, decrease adverse effects in the gastrointestinal tract, and enhance immune response. Nanomaterials can target organs and tissues. Nanomaterials are found to be effectively compatible by interacting with functional foods and nutraceuticals. Applications of these nanomaterials are novel strategies in food industries such as food safety, food processing, food quality, food packaging, and food labeling. Various functions like detection of toxins and pathogens; production of biocompatible packaging; enhancement in color, flavor, and aroma; processing edible film, and sensing authenticity of food product are being accomplished with no toxicity. This review provides a systematic study on the biocompatibility of nanomaterials. It highlights the synthesis of biocompatible nanomaterials and advanced functions of these nanomaterials in the production area, processing industry, safety improvement, quality control, edible packaging films, biocompatibility, current developments, legislations and regulations for Nano-products, health and safety concerns, toxicity and public perceptions for use of nanomaterials.
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Affiliation(s)
| | - Bakhtawar Shafique
- Institute of Food Science and Nutrition, University of Sargodha, Sargodha, Pakistan
| | - Abdur Rehman
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Arshad Mehmood
- Beijing Advance Innovation Center for Food Nutrition and Human Health, School of Food and Health, Beijing Technology and Business University, Beijing, China
| | - Ahmad Ali
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Syeda Mahvish Zahra
- Institute of Food Science and Nutrition, University of Sargodha, Sargodha, Pakistan
- Department of Environmental Design, Health and Nutritional Sciences, Allama Iqbal Open University, Islamabad, Pakistan
- *Correspondence: Syeda Mahvish Zahra ;
| | - Ume Roobab
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Ajay Singh
- Department of Food Technology, Mata Gujri College, Fatehgarh Sahib, India
| | - Salam A. Ibrahim
- Food Microbiology and Biotechnology Laboratory, North Carolina Agricultural and Technical State University, Greensboro, NC, United States
- Salam A. Ibrahim
| | - Shahida Anusha Siddiqui
- Technical University of Munich, Campus Straubing for Biotechnology and Sustainability, Straubing, Germany
- German Institute of Food Technologies (DIL e.V.), (Deutsches Institut für Lebensmitteltechnik (English version: German Institute of Food Technologies)), Quakenbrück, Germany
- Shahida Anusha Siddiqui
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25
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Ye Y, Ma Y, Zhu J. The future of dry powder inhaled therapy: Promising or Discouraging for systemic disorders? Int J Pharm 2022; 614:121457. [PMID: 35026316 PMCID: PMC8744475 DOI: 10.1016/j.ijpharm.2022.121457] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/02/2022] [Accepted: 01/05/2022] [Indexed: 12/25/2022]
Abstract
Dry powder inhalation therapy has been shown to be an effective method for treating respiratory diseases like asthma, Chronic Obstructive Pulmonary Diseases and Cystic Fibrosis. It has also been widely accepted and used in clinical practices. Such success has led to great interest in inhaled therapy on treating systemic diseases in the past two decades. The current coronavirus (COVID-19) pandemic also has increased such interest and is triggering more potential applications of dry powder inhalation therapy in vaccines and antivirus drugs. Would the inhaled dry powder therapy on systemic disorders be as encouraging as expected? This paper reviews the marketed and in-development dry powder inhaler (DPI) products on the treatment of systemic diseases, their status in clinical trials, as well as the potential for COVID-19 treatment. The advancements and unmet problems on DPI systems are also summarized. With countless attempts behind and more challenges ahead, it is believed that the dry powder inhaled therapy for the treatment of systemic disorders still holds great potential and promise.
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Affiliation(s)
- Yuqing Ye
- University of Western Ontario, 1151 Richmond Street, London, N6A 3K7, Canada; Ningbo Inhale Pharma, 2260 Yongjiang Avenue, Ningbo National High-Tech Zone, Ningbo, 315000, China
| | - Ying Ma
- University of Western Ontario, 1151 Richmond Street, London, N6A 3K7, Canada; Ningbo Inhale Pharma, 2260 Yongjiang Avenue, Ningbo National High-Tech Zone, Ningbo, 315000, China
| | - Jesse Zhu
- University of Western Ontario, 1151 Richmond Street, London, N6A 3K7, Canada.
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26
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Amaral M, Cruz N, Rosa A, Nogueira B, Costa D, Santos F, Brazão M, Policarpo P, Mateus R, Kobozev Y, Reis CP. An update of advanced nanoplatforms for Glioblastoma Multiforme Management. EXCLI JOURNAL 2021; 20:1544-1570. [PMID: 34924904 PMCID: PMC8678060 DOI: 10.17179/excli2021-4393] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 11/05/2021] [Indexed: 12/12/2022]
Abstract
Glioblastoma multiforme (GBM) is a very aggressive and heterogeneous glioma. Currently, GBM is treated with a combination of surgery, radiotherapy, chemotherapy (e.g. temozolamide) and Tumour Treating Fields. Unfortunately, the mean survival is still around 15 months. This poor prognosis is associated with therapy resistance, tumor recurrence, and limited delivery of drugs due to the blood-brain barrier nature. Nanomedicine, the application of nanotechnology to medicine, has revolutionized many health fields, specifically cancer diagnosis and treatment. This review explores the particularities of different nanosystems (i.e., superparamagnetic, polymeric and gold nanoparticles, and liposomes) as well as how they can be applied to the treatment and diagnosis of GBM. As described, the most of the cited examples are on the preclinical phase; however, positive results were obtained and thus, the distance to achieve an effective treatment is shorter every day.
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Affiliation(s)
- Mariana Amaral
- iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Nuno Cruz
- iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Ana Rosa
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Beatriz Nogueira
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Diana Costa
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Francisco Santos
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Mariana Brazão
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Pedro Policarpo
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Rita Mateus
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Yan Kobozev
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Catarina Pinto Reis
- iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
- IBEB, Biophysics and Biomedical Engineering, Faculty of Sciences, Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal
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27
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Loh JS, Tan LKS, Lee WL, Ming LC, How CW, Foo JB, Kifli N, Goh BH, Ong YS. Do Lipid-based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids? Cancers (Basel) 2021; 13:5346. [PMID: 34771511 PMCID: PMC8582402 DOI: 10.3390/cancers13215346] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/09/2021] [Accepted: 06/10/2021] [Indexed: 12/12/2022] Open
Abstract
Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.
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Affiliation(s)
- Jian Sheng Loh
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Malaysia; (J.S.L.); (C.W.H.)
| | - Li Kar Stella Tan
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor’s University, Jalan Taylors 1, Subang Jaya 47500, Malaysia; (L.K.S.T.); (J.B.F.)
| | - Wai Leng Lee
- School of Science, Monash University Malaysia, Subang Jaya 47500, Malaysia;
| | - Long Chiau Ming
- PAP Rashidah Sa’adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Gadong BE1410, Brunei; (L.C.M.); (N.K.)
| | - Chee Wun How
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Malaysia; (J.S.L.); (C.W.H.)
- Health and Well-Being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Subang Jaya 47500, Malaysia
| | - Jhi Biau Foo
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor’s University, Jalan Taylors 1, Subang Jaya 47500, Malaysia; (L.K.S.T.); (J.B.F.)
- Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor’s University, Jalan Taylors 1, Subang Jaya 47500, Malaysia
| | - Nurolaini Kifli
- PAP Rashidah Sa’adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Gadong BE1410, Brunei; (L.C.M.); (N.K.)
| | - Bey Hing Goh
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Malaysia; (J.S.L.); (C.W.H.)
- Biofunctional Molecule Exploratory Research Group (BMEX), School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Malaysia
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yong Sze Ong
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Malaysia; (J.S.L.); (C.W.H.)
- Health and Well-Being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Subang Jaya 47500, Malaysia
- Biofunctional Molecule Exploratory Research Group (BMEX), School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Malaysia
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28
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Abd-Algaleel SA, Metwally AA, Abdel-Bar HM, Kassem DH, Hathout RM. Synchronizing In Silico, In Vitro, and In Vivo Studies for the Successful Nose to Brain Delivery of an Anticancer Molecule. Mol Pharm 2021; 18:3763-3776. [PMID: 34460250 DOI: 10.1021/acs.molpharmaceut.1c00276] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Sesamol is a sesame seed constituent with reported activity against many types of cancer. In this work, two types of nanocarriers, solid lipid nanoparticles (SLNs) and polymeric nanoparticles (PNs), were exploited to improve sesamol efficiency against the glioma cancer cell line. The ability of the proposed systems for efficient brain targeting intranasally was also inspected. By the aid of two docking programs, the virtual loading pattern inside these nanocarriers was matched to the real experimental results. Interactions involved in sesamol-carrier binding were also assessed, followed by a discussion of how different scoring functions account for these interactions. The study is an extension of the computer-assisted drug formulation design series, which represents a promising initiative for an upcoming industrial innovation. The results proved the power of combined in silico tools in predicting members with the highest sesamol payload suitable for delivering a sufficient dose to the brain. Among nine carriers, glyceryl monostearate (GMS) and polycaprolactone (PCL) scored the highest sesamol payload practically and computationally. The EE % was 66.09 ± 0.92 and 61.73 ± 0.47 corresponding to a ΔG (binding energy) of -8.85 ± 0.16 and -5.04 ± 0.11, respectively. Dynamic light scattering evidenced the formation of 215.1 ± 7.2 nm and 414.25 ± 1.6 nm nanoparticles, respectively. Both formulations demonstrated an efficient cytotoxic effect and brain-targeting ability compared to the sesamol solution. This was evidenced by low IC50 (38.50 ± 10.37 μM and 27.81 ± 2.76 μM) and high drug targeting efficiency (7.64 ± 1.89-fold and 13.72 ± 4.1-fold) and direct transport percentages (86.12 ± 3.89 and 92.198 ± 2.09) for GMS-SLNs and PCL-PNs, respectively. The results also showed how different formulations, having different compositions and characteristics, could affect the cytotoxic and targeting ability.
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Affiliation(s)
| | - Abdelkader A Metwally
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.,Department of Pharmaceutics, Faculty of Pharmacy, Health Sciences Center, Kuwait University, Safat, 13110 Kuwait, Kuwait
| | - Hend Mohamed Abdel-Bar
- Department of Pharmaceutics, Faculty of Pharmacy, University of Sadat City, Menofia 32897, Egypt
| | - Dina H Kassem
- Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
| | - Rania M Hathout
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
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29
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Kamenska T, Abrashev M, Georgieva M, Krasteva N. Impact of Polyethylene Glycol Functionalization of Graphene Oxide on Anticoagulation and Haemolytic Properties of Human Blood. MATERIALS (BASEL, SWITZERLAND) 2021; 14:4853. [PMID: 34500942 PMCID: PMC8432731 DOI: 10.3390/ma14174853] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/09/2021] [Accepted: 08/24/2021] [Indexed: 11/16/2022]
Abstract
Graphene oxide (GO) is one of the most explored nanomaterials in recent years. It has numerous biomedical applications as a nanomaterial including drug and gene delivery, contrast imaging, cancer treatment, etc. Since most of these applications need intravenous administration of graphene oxide and derivatives, the evaluation of their haemocompatibility is an essential preliminary step for any of the developed GO applications. Plentiful data show that functionalization of graphene oxide nanoparticles with polyethylene glycol (PEG) increases biocompatibility, thus allowing PEGylated GO to elicit less dramatic blood cell responses than their pristine counterparts. Therefore, in this work, we PEGylated graphene oxide nanoparticles and evaluated the effects of their PEGylation on the structure and function of human blood components, especially on the morphology and the haemolytic potential of red blood cells (RBCs). Further, we studied the effect of PEGylation on some blood coagulation factors, including plasma fibrinogen as well as on the activated partial thromboplastin (aPTT), prothrombin time (PT) and platelet aggregation. Our findings provide important information on the mechanisms through which PEGylation increases GO compatibility with human blood cells. These data are crucial for the molecular design and biomedical applications of PEGylated graphene oxide nanomaterials in the future.
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Affiliation(s)
- Trayana Kamenska
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Street Bl. 21, 1113 Sofia, Bulgaria;
| | - Miroslav Abrashev
- Faculty of Physics, Sofia University “St. Kliment Ohridski”, 5 James Bourchier Blvd., 1164 Sofia, Bulgaria;
| | - Milena Georgieva
- Institute of Molecular Biology “Acad. R. Tsanev”, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Street Bl. 21, 1113 Sofia, Bulgaria;
| | - Natalia Krasteva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Street Bl. 21, 1113 Sofia, Bulgaria;
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30
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Characterizing block-copolymer micelles used in nanomedicines via solution static scattering techniques. Polym J 2021. [DOI: 10.1038/s41428-021-00489-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
AbstractBlock copolymers are well recognized as excellent nanotools for delivering hydrophobic drugs. The formulation of such delivery nanoparticles requires robust characterization and clarification of the critical quality attributes correlating with the safety and efficacy of the drug before applying to regulatory authorities for approval. Static solution scattering from block copolymers is one such technique. This paper first outlines the theoretical background and current models for analyzing this scattering and then presents an overview of our recent studies on block copolymers.
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31
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Sipos B, Katona G, Csóka I. A Systematic, Knowledge Space-Based Proposal on Quality by Design-Driven Polymeric Micelle Development. Pharmaceutics 2021; 13:pharmaceutics13050702. [PMID: 34065825 PMCID: PMC8150990 DOI: 10.3390/pharmaceutics13050702] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/07/2021] [Accepted: 05/10/2021] [Indexed: 02/04/2023] Open
Abstract
Nanoparticle research and development for pharmaceuticals is a challenging task in the era of personalized medicine. Specialized and increased patient expectations and requirements for proper therapy adherence, as well as sustainable environment safety and toxicology topics raise the necessity of well designed, advanced and smart drug delivery systems on the market. These stakeholder expectations and social responsibility of pharma sector open the space and call new methods on the floor for new strategic development tools, like Quality by Design (QbD) thinking. The extended model, namely the R&D QbD proved to be useful in case of complex and/or high risk/expectations containing or aiming developments. This is the case when we formulate polymeric micelles as promising nanotherapeutics; the risk assessment and knowledge-based quality targeted QbD approach provides a promising tool to support the development process. Based on risk assessment, many factors pose great risk in the manufacturing process and affect the quality, efficacy and safety profile. The quality-driven strategic development pathway, based on deep prior knowledge and an involving iterative risk estimation and management phases has proven to be an adequate tool, being able to handle their sensitive stability issues and make them efficient therapeutic aids in case of several diseases.
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32
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Ferreira-Silva M, Faria-Silva C, Viana Baptista P, Fernandes E, Ramos Fernandes A, Corvo ML. Liposomal Nanosystems in Rheumatoid Arthritis. Pharmaceutics 2021; 13:pharmaceutics13040454. [PMID: 33801603 PMCID: PMC8065723 DOI: 10.3390/pharmaceutics13040454] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/19/2021] [Accepted: 03/25/2021] [Indexed: 02/06/2023] Open
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints and results in reduced patient quality of life due to its chronic nature and several comorbidities. RA is also associated with a high socioeconomic burden. Currently, several available therapies minimize symptoms and prevent disease progression. However, more effective treatments are needed due to current therapies' severe side-effects, especially under long-term use. Drug delivery systems have demonstrated their clinical importance-with several nanocarriers present in the market-due to their capacity to improve therapeutic drug index, for instance, by enabling passive or active targeting. The first to achieve market authorization were liposomes that still represent a considerable part of approved delivery systems. In this manuscript, we review the role of liposomes in RA treatment, address preclinical studies and clinical trials, and discuss factors that could hamper a successful clinical translation. We also suggest some alterations that could potentially improve their progression to the market.
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Affiliation(s)
- Margarida Ferreira-Silva
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (M.F.-S.); (C.F.-S.)
| | - Catarina Faria-Silva
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (M.F.-S.); (C.F.-S.)
| | - Pedro Viana Baptista
- Unidade de Ciências Biomoleculares Aplicadas UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal;
| | - Eduarda Fernandes
- Associated Laboratory for Green Chemistry of the Network of Chemistry and Technology (LAQV, REQUIMTE), Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal;
| | - Alexandra Ramos Fernandes
- Unidade de Ciências Biomoleculares Aplicadas UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal;
- Correspondence: (A.R.F.); (M.L.C.)
| | - Maria Luísa Corvo
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; (M.F.-S.); (C.F.-S.)
- Correspondence: (A.R.F.); (M.L.C.)
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González-Fernández FM, Bianchera A, Gasco P, Nicoli S, Pescina S. Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation. Pharmaceutics 2021; 13:447. [PMID: 33810399 PMCID: PMC8067198 DOI: 10.3390/pharmaceutics13040447] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/16/2021] [Accepted: 03/23/2021] [Indexed: 02/07/2023] Open
Abstract
Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected. Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability. Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems. The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework. Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application. This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process. This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration. A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research.
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Affiliation(s)
- Felipe M. González-Fernández
- Department of Food and Drug, University of Parma, Viale Parco Area delle Scienze, 27/a, 43124 Parma, Italy; (A.B.); (S.N.)
- Nanovector S.r.l., Via Livorno, 60, 10144 Torino, Italy;
| | - Annalisa Bianchera
- Department of Food and Drug, University of Parma, Viale Parco Area delle Scienze, 27/a, 43124 Parma, Italy; (A.B.); (S.N.)
| | - Paolo Gasco
- Nanovector S.r.l., Via Livorno, 60, 10144 Torino, Italy;
| | - Sara Nicoli
- Department of Food and Drug, University of Parma, Viale Parco Area delle Scienze, 27/a, 43124 Parma, Italy; (A.B.); (S.N.)
| | - Silvia Pescina
- Department of Food and Drug, University of Parma, Viale Parco Area delle Scienze, 27/a, 43124 Parma, Italy; (A.B.); (S.N.)
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Surfactants, Nanomedicines and Nanocarriers: A Critical Evaluation on Clinical Trials. Pharmaceutics 2021; 13:pharmaceutics13030381. [PMID: 33805639 PMCID: PMC7999832 DOI: 10.3390/pharmaceutics13030381] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/06/2021] [Accepted: 03/09/2021] [Indexed: 12/20/2022] Open
Abstract
Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomedicines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly for those authorized in the European Economic Area. We retrieve, analyze and report data available at the Clinical Trial Office of the Italian Medicines Agency (AIFA), increasing the transparency and availability of relevant information. An analysis of quality documentation submitted along with clinical trials authorized by the AIFA in 2018 was carried out, focusing on the key terms "surfactant", "nanomedicine" and "nanocarrier". Results suggest potential indications and inputs for further reflection and actions for regulators to actively and safely drive innovation from a regulatory perspective and to transpose upcoming evolution of clinical trials within a strong regulatory framework.
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Ferreira-Silva M, Faria-Silva C, Baptista PV, Fernandes E, Fernandes AR, Corvo ML. Drug delivery nanosystems targeted to hepatic ischemia and reperfusion injury. Drug Deliv Transl Res 2021; 11:397-410. [PMID: 33660214 DOI: 10.1007/s13346-021-00915-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2021] [Indexed: 02/07/2023]
Abstract
Hepatic ischemia and reperfusion injury (IRI) is an acute inflammatory process that results from surgical interventions, such as liver resection surgery or transplantation, or hemorrhagic shock. This pathology has become a severe clinical issue, due to the increasing incidence of hepatic cancer and the high number of liver transplants. So far, an effective treatment has not been implemented in the clinic. Despite its importance, hepatic IRI has not attracted much interest as an inflammatory disease, and only a few reviews addressed it from a therapeutic perspective with drug delivery nanosystems. In the last decades, drug delivery nanosystems have proved to be a major asset in therapy because of their ability to optimize drug delivery, either by passive or active targeting. Passive targeting is achieved through the enhanced permeability and retention (EPR) effect, a main feature in inflammation that allows the accumulation of the nanocarriers in inflammation sites, enabling a higher efficacy of treatment than conventional therapies. These systems also can be actively targeted to specific compounds, such as inflammatory markers and overexpressed receptors in immune system intermediaries, allowing an even more specialized therapy that have already showed encouraging results. In this manuscript, we review drug delivery nanosystems designed for hepatic IRI treatment, addressing their current state in clinical trials, discussing the main hurdles that hinder their successful translation to the market and providing some suggestions that could potentially advance their clinical translation.
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Affiliation(s)
- Margarida Ferreira-Silva
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal
| | - Catarina Faria-Silva
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal
| | - Pedro Viana Baptista
- UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal
| | - Eduarda Fernandes
- LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal
| | - Alexandra Ramos Fernandes
- UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal
| | - Maria Luísa Corvo
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
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Di Francesco M, Celia C, Cristiano MC, d’Avanzo N, Ruozi B, Mircioiu C, Cosco D, Di Marzio L, Fresta M. Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer. ACS OMEGA 2021; 6:2973-2989. [PMID: 33553916 PMCID: PMC7860091 DOI: 10.1021/acsomega.0c05350] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 12/08/2020] [Indexed: 05/06/2023]
Abstract
Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer.
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Affiliation(s)
- Martina Di Francesco
- Department
of Health Sciences, University of Catanzaro
“Magna Graecia”, Campus Universitario “S. Venuta” s.n.c., 88100 Catanzaro, Italy
- Laboratory
of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy
| | - Christian Celia
- Department
of Pharmacy, University of Chieti−Pescara
“G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
| | - Maria Chiara Cristiano
- Department
of Clinical and Experimental Medicine, University
of Catanzaro “Magna Graecia”, Campus Universitario “S. Venuta”
s.n.c., 88100 Catanzaro, Italy
| | - Nicola d’Avanzo
- Department
of Health Sciences, University of Catanzaro
“Magna Graecia”, Campus Universitario “S. Venuta” s.n.c., 88100 Catanzaro, Italy
- Department
of Pharmacy, University of Chieti−Pescara
“G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
| | - Barbara Ruozi
- Department
of Life Sciences, University of Modena and
Reggio Emilia, Via Campi
183, I-41100 Modena, Italy
| | - Constantin Mircioiu
- Department
of Applied Mathematics and Biostatistics, Faculty of Pharmacy, “Carol Davila” University of Medicine
and Pharmacy, 020956 Bucharest, Romania
| | - Donato Cosco
- Department
of Health Sciences, University of Catanzaro
“Magna Graecia”, Campus Universitario “S. Venuta” s.n.c., 88100 Catanzaro, Italy
| | - Luisa Di Marzio
- Department
of Pharmacy, University of Chieti−Pescara
“G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy
| | - Massimo Fresta
- Department
of Health Sciences, University of Catanzaro
“Magna Graecia”, Campus Universitario “S. Venuta” s.n.c., 88100 Catanzaro, Italy
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Savi M, Bocchi L, Cacciani F, Vilella R, Buschini A, Perotti A, Galati S, Montalbano S, Pinelli S, Frati C, Corradini E, Quaini F, Ruotolo R, Stilli D, Zaniboni M. Cobalt oxide nanoparticles induce oxidative stress and alter electromechanical function in rat ventricular myocytes. Part Fibre Toxicol 2021; 18:1. [PMID: 33407654 PMCID: PMC7788732 DOI: 10.1186/s12989-020-00396-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/21/2020] [Indexed: 02/08/2023] Open
Abstract
Background Nanotoxicology is an increasingly relevant field and sound paradigms on how inhaled nanoparticles (NPs) interact with organs at the cellular level, causing harmful conditions, have yet to be established. This is particularly true in the case of the cardiovascular system, where experimental and clinical evidence shows morphological and functional damage associated with NP exposure. Giving the increasing interest on cobalt oxide (Co3O4) NPs applications in industrial and bio-medical fields, a detailed knowledge of the involved toxicological effects is required, in view of assessing health risk for subjects/workers daily exposed to nanomaterials. Specifically, it is of interest to evaluate whether NPs enter cardiac cells and interact with cell function. We addressed this issue by investigating the effect of acute exposure to Co3O4-NPs on excitation-contraction coupling in freshly isolated rat ventricular myocytes. Results Patch clamp analysis showed instability of resting membrane potential, decrease in membrane electrical capacitance, and dose-dependent decrease in action potential duration in cardiomyocytes acutely exposed to Co3O4-NPs. Motion detection and intracellular calcium fluorescence highlighted a parallel impairment of cell contractility in comparison with controls. Specifically, NP-treated cardiomyocytes exhibited a dose-dependent decrease in the fraction of shortening and in the maximal rate of shortening and re-lengthening, as well as a less efficient cytosolic calcium clearing and an increased tendency to develop spontaneous twitches. In addition, treatment with Co3O4-NPs strongly increased ROS accumulation and induced nuclear DNA damage in a dose dependent manner. Finally, transmission electron microscopy analysis demonstrated that acute exposure did lead to cellular internalization of NPs. Conclusions Taken together, our observations indicate that Co3O4-NPs alter cardiomyocyte electromechanical efficiency and intracellular calcium handling, and induce ROS production resulting in oxidative stress that can be related to DNA damage and adverse effects on cardiomyocyte functionality. Supplementary Information The online version contains supplementary material available at 10.1186/s12989-020-00396-6.
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Affiliation(s)
- Monia Savi
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy.
| | - Leonardo Bocchi
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Francesca Cacciani
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Rocchina Vilella
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Annamaria Buschini
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Alessio Perotti
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Serena Galati
- Centre for Molecular and Translational Oncology (COMT), University of Parma, Parma, Italy
| | - Serena Montalbano
- Centre for Molecular and Translational Oncology (COMT), University of Parma, Parma, Italy
| | - Silvana Pinelli
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Caterina Frati
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Emilia Corradini
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Federico Quaini
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Roberta Ruotolo
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Donatella Stilli
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy
| | - Massimiliano Zaniboni
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/a, 43124, Parma, Italy.
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Mosselhy DA, Assad M, Sironen T, Elbahri M. Nanotheranostics: A Possible Solution for Drug-Resistant Staphylococcus aureus and their Biofilms? NANOMATERIALS (BASEL, SWITZERLAND) 2021; 11:E82. [PMID: 33401760 PMCID: PMC7824312 DOI: 10.3390/nano11010082] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/24/2020] [Accepted: 12/30/2020] [Indexed: 12/14/2022]
Abstract
Staphylococcus aureus is a notorious pathogen that colonizes implants (orthopedic and breast implants) and wounds with a vicious resistance to antibiotic therapy. Methicillin-resistant S. aureus (MRSA) is a catastrophe mainly restricted to hospitals and emerged to community reservoirs, acquiring resistance and forming biofilms. Treating biofilms is problematic except via implant removal or wound debridement. Nanoparticles (NPs) and nanofibers could combat superbugs and biofilms and rapidly diagnose MRSA. Nanotheranostics combine diagnostics and therapeutics into a single agent. This comprehensive review is interpretative, utilizing mainly recent literature (since 2016) besides the older remarkable studies sourced via Google Scholar and PubMed. We unravel the molecular S. aureus resistance and complex biofilm. The diagnostic properties and detailed antibacterial and antibiofilm NP mechanisms are elucidated in exciting stories. We highlight the challenges of bacterial infections nanotheranostics. Finally, we discuss the literature and provide "three action appraisals". (i) The first appraisal consists of preventive actions (two wings), avoiding unnecessary hospital visits, hand hygiene, and legislations against over-the-counter antibiotics as the general preventive wing. Our second recommended preventive wing includes preventing the adverse side effects of the NPs from resistance and toxicity by establishing standard testing procedures. These standard procedures should provide breakpoints of bacteria's susceptibility to NPs and a thorough toxicological examination of every single batch of synthesized NPs. (ii) The second appraisal includes theranostic actions, using nanotheranostics to diagnose and treat MRSA, such as what we call "multifunctional theranostic nanofibers. (iii) The third action appraisal consists of collaborative actions.
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Affiliation(s)
- Dina A. Mosselhy
- Nanochemistry and Nanoengineering, Department of Chemistry and Materials Science, School of Chemical Engineering, Aalto University, 02150 Espoo, Finland;
- Microbiological Unit, Fish Diseases Department, Animal Health Research Institute, Dokki, Giza 12618, Egypt
- Department of Virology, Faculty of Medicine, University of Helsinki, P.O. Box 21, 00014 Helsinki, Finland;
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, 00014 Helsinki, Finland
| | - Mhd Assad
- Nanochemistry and Nanoengineering, Department of Chemistry and Materials Science, School of Chemical Engineering, Aalto University, 02150 Espoo, Finland;
| | - Tarja Sironen
- Department of Virology, Faculty of Medicine, University of Helsinki, P.O. Box 21, 00014 Helsinki, Finland;
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, 00014 Helsinki, Finland
| | - Mady Elbahri
- Nanochemistry and Nanoengineering, Department of Chemistry and Materials Science, School of Chemical Engineering, Aalto University, 02150 Espoo, Finland;
- Nanochemistry and Nanoengineering, Institute for Materials Science, Faculty of Engineering, Kiel University, 24143 Kiel, Germany
- Center for Nanotechnology, Zewail City of Science and Technology, Sheikh Zayed District, Giza 12588, Egypt
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Graphene Oxide as a Nanocarrier for Biochemical Molecules: Current Understanding and Trends. Processes (Basel) 2020. [DOI: 10.3390/pr8121636] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The development of an advanced and efficient drug delivery system with significant improvement in its efficacy and enhanced therapeutic value is one of the critical challenges in modern medicinal biology. The integration of nanomaterial science with molecular and cellular biology has helped in the advancement and development of novel drug delivery nanocarrier systems with precision and decreased side effects. The design and synthesis of nanocarriers using graphene oxide (GO) have been rapidly growing over the past few years. Due to its remarkable physicochemical properties, GO has been extensively used in efforts to construct nanocarriers with high specificity, selectivity, and biocompatibility, and low cytotoxicity. The focus of this review is to summarize and address recent uses of GO-based nanocarriers and the improvements as efficient drug delivery systems. We briefly describe the concepts and challenges associated with nanocarrier systems followed by providing critical examples of GO-based delivery of drug molecules and genes. Finally, the review delivers brief conclusions on the current understanding and prospects of nanocarrier delivery systems.
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40
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Zeb A, Rana I, Choi HI, Lee CH, Baek SW, Lim CW, Khan N, Arif ST, Sahar NU, Alvi AM, Shah FA, Din FU, Bae ON, Park JS, Kim JK. Potential and Applications of Nanocarriers for Efficient Delivery of Biopharmaceuticals. Pharmaceutics 2020; 12:E1184. [PMID: 33291312 PMCID: PMC7762162 DOI: 10.3390/pharmaceutics12121184] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/02/2020] [Accepted: 12/02/2020] [Indexed: 12/13/2022] Open
Abstract
During the past two decades, the clinical use of biopharmaceutical products has markedly increased because of their obvious advantages over conventional small-molecule drug products. These advantages include better specificity, potency, targeting abilities, and reduced side effects. Despite the substantial clinical and commercial success, the macromolecular structure and intrinsic instability of biopharmaceuticals make their formulation and administration challenging and render parenteral delivery as the only viable option in most cases. The use of nanocarriers for efficient delivery of biopharmaceuticals is essential due to their practical benefits such as protecting from degradation in a hostile physiological environment, enhancing plasma half-life and retention time, facilitating absorption through the epithelium, providing site-specific delivery, and improving access to intracellular targets. In the current review, we highlight the clinical and commercial success of biopharmaceuticals and the overall applications and potential of nanocarriers in biopharmaceuticals delivery. Effective applications of nanocarriers for biopharmaceuticals delivery via invasive and noninvasive routes (oral, pulmonary, nasal, and skin) are presented here. The presented data undoubtedly demonstrate the great potential of combining nanocarriers with biopharmaceuticals to improve healthcare products in the future clinical landscape. In conclusion, nanocarriers are promising delivery tool for the hormones, cytokines, nucleic acids, vaccines, antibodies, enzymes, and gene- and cell-based therapeutics for the treatment of multiple pathological conditions.
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Affiliation(s)
- Alam Zeb
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Isra Rana
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Ho-Ik Choi
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Cheol-Ho Lee
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Seong-Woong Baek
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Chang-Wan Lim
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Namrah Khan
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Sadia Tabassam Arif
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Najam us Sahar
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Arooj Mohsin Alvi
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Fawad Ali Shah
- Riphah Institute of Pharmaceutical Science, Riphah International University, Islamabad 44000, Pakistan; (I.R.); (N.K.); (S.T.A.); (N.u.S.); (A.M.A.); (F.A.S.)
| | - Fakhar ud Din
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan;
| | - Ok-Nam Bae
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
| | - Jeong-Sook Park
- Institute of Drug Research and Development, College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
| | - Jin-Ki Kim
- Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Gyeonggi-do 15588, Korea; (A.Z.); (H.-I.C.); (C.-H.L.); (S.-W.B.); (C.-W.L.); (O.-N.B.)
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Németh Z, Pallagi E, Dobó DG, Csóka I. A Proposed Methodology for a Risk Assessment-Based Liposome Development Process. Pharmaceutics 2020; 12:E1164. [PMID: 33260443 PMCID: PMC7760874 DOI: 10.3390/pharmaceutics12121164] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/24/2020] [Accepted: 11/27/2020] [Indexed: 12/18/2022] Open
Abstract
The requirements of a liposomal formulation vary depending on the pharmaceutical indication, the target patient population, and the corresponding route of administration. Different preparation methods require various material attributes (MAs) (properties and characteristics of the components) and process parameters (PPs) (settings of the preparation method). The identification of the quality target product profile for a liposome-based formulation, the critical quality attributes of the liposomes, and the possible MAs and PPs that may influence the key characteristics of the vesicles facilitates pharmaceutical research. Researchers can systematise their knowledge by using the quality by design (QbD) approach. The potential factors that influence the quality of the product can be collected and studied through a risk assessment process. In this paper, the requirements of a liposome formulation prepared via the thin-film hydration preparation technique are presented; furthermore, the possible factors that have an impact on the quality of the final product and have to be considered and specified during the development of a liposomal formulation are herein identified and collected. The understanding and the application of these elements of QbD in the pharmaceutical developments help to influence the quality, the achievements, and the success of the formulated product.
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Affiliation(s)
| | | | | | - Ildikó Csóka
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary; (Z.N.); (E.P.); or (D.G.D.)
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Chang JH, Chen PJ, Arul MR, Dutra EH, Nanda R, Kumbar SG, Yadav S. Injectable RANKL sustained release formulations to accelerate orthodontic tooth movement. Eur J Orthod 2020; 42:317-325. [PMID: 31147678 DOI: 10.1093/ejo/cjz027] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Accelerating orthodontic tooth movement (OTM) through biologically effective methods, such as increasing osteoclast-mediated alveolar resorption, could effectively shorten treatment time. OBJECTIVE To evaluate an injectable formulation containing receptor activator of nuclear factor kappa-B ligand (RANKL) on the OTM. MATERIALS AND METHODS We fabricated a RANKL formulation from 100 µl of 100 µg/ml RANKL adsorbed on 10 mg of poly(lactic acid-co-glycolic acid) microspheres embedded in a 10 wt% aqueous hydroxyethyl cellulose carrier gel. We characterized these formulations for the rate of RANKL release, and then tested for bioactivity using in vitro cell culture. In vivo OTM studies were conducted using 15 week old male Wistar rats for 14 days. We injected the RANKL formulations palatal to the left maxillary first molar and accomplished OTM with a nickel-titanium (NiTi) coil spring applying 5-8 g force. Control groups involved the application of NiTi coil spring with and without placebo formulation. The outcome measure included the distance of tooth movement, bone volume fraction, tissue density, and root volume determined with micro-computed tomography. We determined the amount of osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS These formulations were able to sustain the release of RANKL for more than 30 days, and the released RANKL showed a positive effect on mice osteoclast precursor cells (RAW 264.7). Reported injectable RANKL formulations were effective in accelerating OTM compared with other control groups, with 129.2 per cent more tooth movement than no formulation and 71.8 per cent more than placebo formulation, corresponding with a significant increase in the amount of TRAP activity. We did not observe any significant differences in root resorption between the groups. CONCLUSION Our study shows a significant increase in OTM with injectable formulations containing RANKL.
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Affiliation(s)
- Joy H Chang
- Division of Orthodontics, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, USA
| | - Po-Jung Chen
- Division of Orthodontics, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, USA
| | - Michael R Arul
- Departments of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, USA.,Departments of Biomedical Engineering, University of Connecticut Health Center, Farmington, USA.,Departments of Materials Science and Engineering, University of Connecticut Health Center, Farmington, USA
| | - Eliane H Dutra
- Division of Orthodontics, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, USA
| | - Ravindra Nanda
- Division of Orthodontics, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, USA
| | - Sangamesh G Kumbar
- Departments of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, USA.,Departments of Biomedical Engineering, University of Connecticut Health Center, Farmington, USA.,Departments of Materials Science and Engineering, University of Connecticut Health Center, Farmington, USA
| | - Sumit Yadav
- Division of Orthodontics, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, USA
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Ferraris C, Cavalli R, Panciani PP, Battaglia L. Overcoming the Blood-Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours. Int J Nanomedicine 2020; 15:2999-3022. [PMID: 32431498 PMCID: PMC7201023 DOI: 10.2147/ijn.s231479] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 04/14/2020] [Indexed: 12/14/2022] Open
Abstract
High-grade gliomas are still characterized by a poor prognosis, despite recent advances in surgical treatment. Chemotherapy is currently practiced after surgery, but its efficacy is limited by aspecific toxicity on healthy cells, tumour cell chemoresistance, poor selectivity, and especially by the blood–brain barrier (BBB). Thus, despite the large number of potential drug candidates, the choice of effective chemotherapeutics is still limited to few compounds. Malignant gliomas are characterized by high infiltration and neovascularization, and leaky BBB (the so-called blood–brain tumour barrier); surgical resection is often incomplete, leaving residual cells that are able to migrate and proliferate. Nanocarriers can favour delivery of chemotherapeutics to brain tumours owing to different strategies, including chemical stabilization of the drug in the bloodstream; passive targeting (because of the leaky vascularization at the tumour site); inhibition of drug efflux mechanisms in endothelial and cancer cells; and active targeting by exploiting carriers and receptors overexpressed at the blood–brain tumour barrier. Within this concern, a suitable nanomedicine-based therapy for gliomas should not be limited to cytotoxic agents, but also target the most important pathogenetic mechanisms, including cell differentiation pathways and angiogenesis. Moreover, the combinatorial approach of cell therapy plus nanomedicine strategies can open new therapeutical opportunities. The major part of attempted preclinical approaches on animal models involves active targeting with protein ligands, but, despite encouraging results, a few number of nanomedicines reached clinical trials, and most of them include drug-loaded nanocarriers free of targeting ligands, also because of safety and scalability concerns.
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Affiliation(s)
- Chiara Ferraris
- Department of Drug Science and Technology, University of Turin, Turin, Italy
| | - Roberta Cavalli
- Department of Drug Science and Technology, University of Turin, Turin, Italy
| | - Pier Paolo Panciani
- Clinic of Neurosurgery, Spedali Civili and University of Brescia, Brescia, Italy
| | - Luigi Battaglia
- Department of Drug Science and Technology, University of Turin, Turin, Italy
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Eleraky NE, Allam A, Hassan SB, Omar MM. Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations. Pharmaceutics 2020; 12:E142. [PMID: 32046289 PMCID: PMC7076477 DOI: 10.3390/pharmaceutics12020142] [Citation(s) in RCA: 168] [Impact Index Per Article: 33.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 01/29/2020] [Accepted: 02/04/2020] [Indexed: 12/16/2022] Open
Abstract
Based on the recent reports of World Health Organization, increased antibiotic resistance prevalence among bacteria represents the greatest challenge to human health. In addition, the poor solubility, stability, and side effects that lead to inefficiency of the current antibacterial therapy prompted the researchers to explore new innovative strategies to overcome such resilient microbes. Hence, novel antibiotic delivery systems are in high demand. Nanotechnology has attracted considerable interest due to their favored physicochemical properties, drug targeting efficiency, enhanced uptake, and biodistribution. The present review focuses on the recent applications of organic (liposomes, lipid-based nanoparticles, polymeric micelles, and polymeric nanoparticles), and inorganic (silver, silica, magnetic, zinc oxide (ZnO), cobalt, selenium, and cadmium) nanosystems in the domain of antibacterial delivery. We provide a concise description of the characteristics of each system that render it suitable as an antibacterial delivery agent. We also highlight the recent promising innovations used to overcome antibacterial resistance, including the use of lipid polymer nanoparticles, nonlamellar liquid crystalline nanoparticles, anti-microbial oligonucleotides, smart responsive materials, cationic peptides, and natural compounds. We further discuss the applications of antimicrobial photodynamic therapy, combination drug therapy, nano antibiotic strategy, and phage therapy, and their impact on evading antibacterial resistance. Finally, we report on the formulations that made their way towards clinical application.
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Affiliation(s)
- Nermin E. Eleraky
- Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt; (N.E.E.); (A.A.)
| | - Ayat Allam
- Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt; (N.E.E.); (A.A.)
- Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut 71515, Egypt
| | - Sahar B. Hassan
- Department of Clinical pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt;
| | - Mahmoud M. Omar
- Department of Pharmaceutics and Industrial Pharmacy, Deraya University, Minia 61768, Egypt
- Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy Sohag University, Sohag 82524, Egypt
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Demetzos C, Kavatzikidou P, Pippa N, Stratakis E. Nanomedicines and Nanosimilars: Looking for a New and Dynamic Regulatory "Astrolabe" Inspired System. AAPS PharmSciTech 2020; 21:65. [PMID: 31933006 DOI: 10.1208/s12249-019-1573-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 10/07/2019] [Indexed: 12/19/2022] Open
Abstract
The application of the nanotechnology in medicine and pharmaceutics opens new horizons in therapeutics. Several nanomedicines are in the market and an increasing number is in clinical trials. But which is the advantage of the medicines in nanoscale? The scientists and the regulatory authorities agree that the size and consequently the physiochemical/biological properties of nanomaterials play a key role in their safety and effectiveness. Additionally, all of them agree that a new scientific-based regulatory landscape is required for the establishment of nanomedicines in the market. The aim of this review is to investigate the parameters that the scientists and the regulatory authorities should take into account in order to build up a dynamic regulatory landscape for nanomedicines. For this reason, we propose an "astrolabe-like system" as the guide for establishing the regulatory approval process. Its function is based on the different physicochemical/biological properties in comparison to low molecular weight drugs.
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Biomimetic cellular vectors for enhancing drug delivery to the lungs. Sci Rep 2020; 10:172. [PMID: 31932600 PMCID: PMC6957529 DOI: 10.1038/s41598-019-55909-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 11/10/2019] [Indexed: 02/01/2023] Open
Abstract
Despite recent advances in drug delivery, the targeted treatment of unhealthy cells or tissues continues to remain a priority. In cancer (much like other pathologies), delivery vectors are designed to exploit physical and biological features of unhealthy tissues that are not always homogenous across the disease. In some cases, shifting the target from unhealthy tissues to the whole organ can represent an advantage. Specifically, the natural organ-specific retention of nanotherapeutics following intravenous administration as seen in the lung, liver, and spleen can be strategically exploited to enhance drug delivery. Herein, we outline the development of a cell-based delivery system using macrophages as a delivery vehicle. When loaded with a chemotherapeutic payload (i.e., doxorubicin), these cellular vectors (CELVEC) were shown to provide continued release within the lung. This study provides proof-of-concept evidence of an alternative class of biomimetic delivery vectors that capitalize on cell size to provide therapeutic advantages for pulmonary treatments.
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Domingues C, Alvarez-Lorenzo C, Concheiro A, Veiga F, Figueiras A. Nanotheranostic Pluronic-Like Polymeric Micelles: Shedding Light into the Dark Shadows of Tumors. Mol Pharm 2019; 16:4757-4774. [DOI: 10.1021/acs.molpharmaceut.9b00945] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Cátia Domingues
- Faculty of Pharmacy, University of Coimbra, Coimbra 3000-295, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra 3004-504, Portugal
- CIMAGO, Center of Investigation on Environment Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra 3004-531, Portugal
| | - Carmen Alvarez-Lorenzo
- Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain
| | - Angel Concheiro
- Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain
| | - Francisco Veiga
- Faculty of Pharmacy, University of Coimbra, Coimbra 3000-295, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra 3004-504, Portugal
| | - Ana Figueiras
- Faculty of Pharmacy, University of Coimbra, Coimbra 3000-295, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra 3004-504, Portugal
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Abstract
Cancer remains one of the most difficult to manage healthcare problems. The last two decades have been considered the golden age of cancer research, with major breakthroughs being announced on a regular basis. However, the major problem regarding cancer treatment is the incapability to selectively target cancer cells, with certain populations of tumors still remaining alive after treatment. The main focus of researchers is to develop treatments that are both effective and selective in targeting malignant cells. In this regard, bioavailability can be increased by overcoming the biological barriers encountered in the active agent’s pathway, creating carrier vehicles that have the ability to target malignant cells and effectively release the active agent. Since its appearance, nanomedicine has provided many answers to these challenges, but still, some expectations were not satisfied. In this review, we focused on the most recent developments in targeted drug delivery. Furthermore, a summary of different types of nanoparticles used to deliver active therapeutic agents in oncology is presented, along with details on the nanodrugs that were clinically approved by the Food and Drug Administration (FDA), until April 2019.
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Kornmueller K, Vidakovic I, Prassl R. Artificial High Density Lipoprotein Nanoparticles in Cardiovascular Research. Molecules 2019; 24:E2829. [PMID: 31382521 PMCID: PMC6695986 DOI: 10.3390/molecules24152829] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 07/31/2019] [Accepted: 08/01/2019] [Indexed: 02/07/2023] Open
Abstract
Lipoproteins are endogenous nanoparticles which are the major transporter of fats and cholesterol in the human body. They play a key role in the regulatory mechanisms of cardiovascular events. Lipoproteins can be modified and manipulated to act as drug delivery systems or nanocarriers for contrast agents. In particular, high density lipoproteins (HDL), which are the smallest class of lipoproteins, can be synthetically engineered either as nascent HDL nanodiscs or spherical HDL nanoparticles. Reconstituted HDL (rHDL) particles are formed by self-assembly of various lipids and apolipoprotein AI (apo-AI). A variety of substances including drugs, nucleic acids, signal emitting molecules, or dyes can be loaded, making them efficient nanocarriers for therapeutic applications or medical diagnostics. This review provides an overview about synthesis techniques, physicochemical properties of rHDL nanoparticles, and structural determinants for rHDL function. We discuss recent developments utilizing either apo-AI or apo-AI mimetic peptides for the design of pharmaceutical rHDL formulations. Advantages, limitations, challenges, and prospects for clinical translation are evaluated with a special focus on promising strategies for the treatment and diagnosis of atherosclerosis and cardiovascular diseases.
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Affiliation(s)
- Karin Kornmueller
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics, Medical University of Graz, Neue Stiftingtalstraße 6/IV, 8010 Graz, Austria
| | - Ivan Vidakovic
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics, Medical University of Graz, Neue Stiftingtalstraße 6/IV, 8010 Graz, Austria
| | - Ruth Prassl
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics, Medical University of Graz, Neue Stiftingtalstraße 6/IV, 8010 Graz, Austria.
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Abumanhal-Masarweh H, da Silva D, Poley M, Zinger A, Goldman E, Krinsky N, Kleiner R, Shenbach G, Schroeder JE, Shklover J, Shainsky-Roitman J, Schroeder A. Tailoring the lipid composition of nanoparticles modulates their cellular uptake and affects the viability of triple negative breast cancer cells. J Control Release 2019; 307:331-341. [PMID: 31238049 DOI: 10.1016/j.jconrel.2019.06.025] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 06/09/2019] [Accepted: 06/21/2019] [Indexed: 11/16/2022]
Abstract
Lipid nanoparticles are used widely as anticancer drug and gene delivery systems. Internalizing into the target cell is a prerequisite for the proper activity of many nanoparticulate drugs. We show here, that the lipid composition of a nanoparticle affects its ability to internalize into triple-negative breast cancer cells. The lipid headgroup had the greatest effect on enhancing cellular uptake compared to other segments of the molecule. Having a receptor-targeted headgroup induced the greatest increase in cellular uptake, followed by cationic amine headgroups, both being superior to neutral (zwitterion) phosphatidylcholine or to negatively-charged headgroups. The lipid tails also affected the magnitude of cellular uptake. Longer acyl chains facilitated greater liposomal cellular uptake compared to shorter tails, 18:0 > 16:0 > 14:0. When having the same lipid tail length, unsaturated lipids were superior to saturated ones, 18:1 > 18:0. Interestingly, liposomes composed of phospholipids having 14:0 or 12:0-carbon-long-tails, such as DMPC and DLPC, decreased cell viability in a concertation dependent manner, due to a destabilizing effect these lipids had on the cancer cell membrane. Contrarily, liposomes composed of phospholipids having longer carbon tails (16:0 and 18:0), such as DPPC and HSPC, enhanced cancer cell proliferation. This effect is attributed to the integration of the exogenous liposomal lipids into the cancer-cell membrane, supporting the proliferation process. Cholesterol is a common lipid additive in nanoscale formulations, rigidifying the membrane and stabilizing its structure. Liposomes composed of DMPC (14:0) showed increased cellular uptake when enriched with cholesterol, both by endocytosis and by fusion. Contrarily, the effect of cholesterol on HSPC (18:0) liposomal uptake was minimal. Furthermore, the concentration of nanoparticles in solution affected their cellular uptake. The higher the concentration of nanoparticles the greater the absolute number of nanoparticles taken up per cell. However, the efficiency of nanoparticle uptake, i.e. the percent of nanoparticles taken up by cells, decreased as the concentration of nanoparticles increased. This study demonstrates that tuning the lipid composition and concentration of nanoscale drug delivery systems can be leveraged to modulate their cellular uptake.
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Affiliation(s)
- Hanan Abumanhal-Masarweh
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel; Russell Berrie Nanotechnology Institute, The Norman Seiden Multidisciplinary Graduate program, Technion-Israel Institute of Technology, Haifa 3200, Israel
| | - Dana da Silva
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Maria Poley
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Assaf Zinger
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Evgenya Goldman
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Nitzan Krinsky
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Ron Kleiner
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Gal Shenbach
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Josh E Schroeder
- Department of Orthopedic Surgery, Hadassah Medical Center, Jerusalem 91120, Israel
| | - Jeny Shklover
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Janna Shainsky-Roitman
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Avi Schroeder
- Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
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