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Aggarwal R, Sheikh A, Akhtar M, Ghazwani M, Hani U, Sahebkar A, Kesharwani P. Understanding gold nanoparticles and their attributes in ovarian cancer therapy. Mol Cancer 2025; 24:88. [PMID: 40108575 PMCID: PMC11924612 DOI: 10.1186/s12943-025-02280-3] [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: 12/03/2024] [Accepted: 02/24/2025] [Indexed: 03/22/2025] Open
Abstract
Ovarian cancer is one the deadliest disease wherein the survival rate is very low. Despite of advances in medical sciences, researches are still at the stage of infancy where patients are succumbing to this malignancy. Multidrug resistance, toxicity, mode of treatment related issues like catheter related complication poises a number of challenges to scientists worldwide. Novel therapy is now thus being focussed to sensitive the cells more towards the treatment. Gold nanoparticles (Au NPs), known for their high biocompatibility, and strong optical and magnetic responses, have emerged as promising agents for both the diagnosis and treatment of ovarian cancer. Owing to physical characteristics, AuNPs may be used as adjuvants in bioimaging, radiotherapy and fluorescence imaging. As a result, these characteristics substantially support AuNPs in biological domains. In addition to their therapeutic potential, Au NPs exhibit strong surface plasmon resonance (SPR) properties, enhancing imaging techniques for early detection of ovarian tumors. Furthermore, chemical properties such as Magnetic Resonance and Imaging Properties, X-ray imaging property, Two-photon or multiphoton imaging, and Optical coherence tomography (OCT) imaging properties enhance the use of Au NPs in diagnosis. This paper highlights the properties, targeting potential and diagnosis and treatment of ovarian cancer by Au NPs has been discussed.
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Affiliation(s)
- Rishabh Aggarwal
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Afsana Sheikh
- Centre for Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, 140401, India
| | - Masheera Akhtar
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Mohammed Ghazwani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Al Faraa, Abha, 62223, Saudi Arabia
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Al Faraa, Abha, 62223, Saudi Arabia
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran.
| | - Prashant Kesharwani
- Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, Madhya Pradesh, 470003, India.
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Cooper CG, Kafetzis KN, Patabendige A, Tagalakis AD. Blood-brain barrier disruption in dementia: Nano-solutions as new treatment options. Eur J Neurosci 2024; 59:1359-1385. [PMID: 38154805 DOI: 10.1111/ejn.16229] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/28/2023] [Accepted: 12/02/2023] [Indexed: 12/30/2023]
Abstract
Candidate drugs targeting the central nervous system (CNS) demonstrate extremely low clinical success rates, with more than 98% of potential treatments being discontinued due to poor blood-brain barrier (BBB) permeability. Neurological conditions were shown to be the second leading cause of death globally in 2016, with the number of people currently affected by neurological disorders increasing rapidly. This increasing trend, along with an inability to develop BBB permeating drugs, is presenting a major hurdle in the treatment of CNS-related disorders, like dementia. To overcome this, it is necessary to understand the structure and function of the BBB, including the transport of molecules across its interface in both healthy and pathological conditions. The use of CNS drug carriers is rapidly gaining popularity in CNS research due to their ability to target BBB transport systems. Further research and development of drug delivery vehicles could provide essential information that can be used to develop novel treatments for neurological conditions. This review discusses the BBB and its transport systems and evaluates the potential of using nanoparticle-based delivery systems as drug carriers for CNS disease with a focus on dementia.
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Affiliation(s)
| | | | - Adjanie Patabendige
- Department of Biology, Edge Hill University, Ormskirk, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
| | - Aristides D Tagalakis
- Department of Biology, Edge Hill University, Ormskirk, UK
- UCL Great Ormond Street Institute of Child Health, University College London, London, UK
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3
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Choi TH, Yoo RJ, Park JY, Kim JY, Ann YC, Park J, Kim JS, Kim K, Shin YJ, Lee YJ, Lee KC, Park J, Chung H, Seok SH, Im HJ, Lee YS. Development of finely tuned liposome nanoplatform for macrophage depletion. J Nanobiotechnology 2024; 22:83. [PMID: 38424578 PMCID: PMC10903058 DOI: 10.1186/s12951-024-02325-7] [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: 04/13/2023] [Accepted: 01/30/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. RESULTS We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. CONCLUSION The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.
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Affiliation(s)
- Tae Hyeon Choi
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea
| | - Ran Ji Yoo
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, South Korea
- Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
| | - Ji Yong Park
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea
| | - Ji Yoon Kim
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Chan Ann
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
- School of Dentistry, Seoul National University, Seoul, South Korea
| | - Jeongbin Park
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea
| | - Jin Sil Kim
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyuwan Kim
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Yu Jin Shin
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong Jin Lee
- Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, South Korea
| | - Kyo Chul Lee
- Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, South Korea
| | - Jisu Park
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
- Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyewon Chung
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
- Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, South Korea
| | - Seung Hyeok Seok
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
- Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyung-Jun Im
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea.
- Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
| | - Yun-Sang Lee
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.
- Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, South Korea.
- Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
- Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
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Zamboni WC, Charlab R, Burckart GJ, Stewart CF. Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents. J Clin Pharmacol 2023; 63 Suppl 2:S85-S102. [PMID: 37942904 DOI: 10.1002/jcph.2326] [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: 05/01/2023] [Accepted: 07/12/2023] [Indexed: 11/10/2023]
Abstract
An objective of the Precision Medicine Initiative, launched in 2015 by the US Food and Drug Administration and National Institutes of Health, is to optimize and individualize dosing of drugs, especially anticancer agents, with high pharmacokinetic and pharmacodynamic variability. The American Society of Clinical Oncology recently reported that 40% of obese patients receive insufficient chemotherapy doses and exposures, which may lead to reduced efficacy, and recommended pharmacokinetic studies to guide appropriate dosing in these patients. These issues will only increase in importance as the incidence of obesity in the population increases. This publication reviews the effects of obesity on (1) tumor biology, development of cancer, and antitumor response; (2) pharmacokinetics and pharmacodynamics of small-molecule anticancer drugs; and (3) pharmacokinetics and pharmacodynamics of complex anticancer drugs, such as carrier-mediated agents and biologics. These topics are not only important from a scientific research perspective but also from a drug development and regulator perspective. Thus, it is important to evaluate the effects of obesity on the pharmacokinetics and pharmacodynamics of anticancer agents in all categories of body habitus and especially in patients who are obese and morbidly obese. As the effects of obesity on the pharmacokinetics and pharmacodynamics of anticancer agents may be highly variable across drug types, the optimal dosing metric and algorithm for difference classes of drugs may be widely different. Thus, studies are needed to evaluate current and novel metrics and methods for measuring body habitus as related to optimizing the dose and reducing pharmacokinetic and pharmacodynamic variability of anticancer agents in patients who are obese and morbidly obese.
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Affiliation(s)
- William C Zamboni
- UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Caroline Institute of Nanomedicine, University of North Carolina, Chapel Hill, NC, USA
| | - Rosane Charlab
- Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Gilbert J Burckart
- Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
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Li H, Qiao W, Shen Y, Xu H, Fan Y, Liu Y, Lan Y, Gong Y, Chen F, Feng S. Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity. Pharmaceutics 2023; 15:pharmaceutics15041269. [PMID: 37111754 PMCID: PMC10145272 DOI: 10.3390/pharmaceutics15041269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/05/2023] [Accepted: 04/17/2023] [Indexed: 04/29/2023] Open
Abstract
Boron nitride nanomaterials are being increasingly recognized as vehicles for cancer drug delivery that increase drug loading and control drug release because of their excellent physicochemical properties and biocompatibility. However, these nanoparticles are often cleared rapidly by the immune system and have poor tumor targeting effects. As a result, biomimetic nanotechnology has emerged to address these challenges in recent times. Cell-derived biomimetic carriers have the characteristics of good biocompatibility, long circulation time, and strong targeting ability. Here, we report a biomimetic nanoplatform (CM@BN/DOX) prepared by encapsulating boron nitride nanoparticles (BN) and doxorubicin (DOX) together using cancer cell membrane (CCM) for targeted drug delivery and tumor therapy. The CM@BN/DOX nanoparticles (NPs) were able to target cancer cells of the same type on its own initiative through homologous targeting of cancer cell membranes. This led to a remarkable increase in cellular uptake. In vitro simulation of an acidic tumor microenvironment could effectively promote drug release from CM@BN/DOX. Furthermore, the CM@BN/DOX complex exhibited an excellent inhibitory effect against homotypic cancer cells. These findings suggest that CM@BN/DOX are promising in targeted drug delivery and potentially personalized therapy against their homologous tumor.
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Affiliation(s)
- Hui Li
- School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Wei Qiao
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Yizhe Shen
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Huashan Xu
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Yuan Fan
- School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Yuxiang Liu
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Yadi Lan
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Yan Gong
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Fuxue Chen
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
| | - Shini Feng
- School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai 200444, China
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6
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Iezzi R, Contegiacomo A, Tanzilli A, Posa A. Combined Therapy (TACE and Percutaneous Treatment). TRANSARTERIAL CHEMOEMBOLIZATION (TACE) 2023:95-105. [DOI: 10.1007/978-3-031-36261-3_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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7
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Mfouo-Tynga IS, Mouinga-Ondeme AG. Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia. Pharmaceuticals (Basel) 2022; 15:ph15101273. [PMID: 36297385 PMCID: PMC9608479 DOI: 10.3390/ph15101273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/08/2022] [Accepted: 10/11/2022] [Indexed: 11/07/2022] Open
Abstract
The recent COVID-19 pandemic outbreak and arising complications during treatments have highlighted and demonstrated again the evolving ability of microorganisms, especially viral resistance to treatment as they develop into new and strong strains. The search for novel and effective treatments to counter the effects of ever-changing viruses is undergoing. Although it is an approved procedure for treating cancer, photodynamic therapy (PDT) was first used against bacteria and has now shown potential against viruses and certain induced diseases. PDT is a multi-stage process and uses photosensitizing molecules (PSs) that accumulate in diseased tissues and eradicates them after being light-activated in the presence of oxygen. In this review, studies describing viruses and their roles in disrupting cell regulation mechanisms and signaling pathways and facilitating tumorigenesis were described. With the development of innovative “or smart” PSs through the use of nanoparticles and two-photon excitation, among other strategies, PDT can boost immune responses, inactivate viral infections, and eradicate neoplastic cells. Visualization and monitoring of biological processes can be achieved in real-time with nanomedicines and better tissue penetration strategies. After photodynamic inactivation of viruses, signaling pathways seem to be restored but the underlying mechanisms are still to be elucidated. Light-mediated treatments are suitable to manage both oncogenic viral infections and induced neoplasia.
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8
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Gbian DL, Omri A. Lipid-Based Drug Delivery Systems for Diseases Managements. Biomedicines 2022; 10:2137. [PMID: 36140237 PMCID: PMC9495957 DOI: 10.3390/biomedicines10092137] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 08/26/2022] [Accepted: 08/27/2022] [Indexed: 11/17/2022] Open
Abstract
Liposomes are tiny lipid-based vesicles composed of one or more lipid bilayers, which facilitate the encapsulation of hydrophilic, lipophilic, and amphiphilic biological active agents. The description of the physicochemical properties, formulation methods, characteristics, mechanisms of action, and large-scale manufacturing of liposomes as delivery systems are deeply discussed. The benefits, toxicity, and limitations of the use of liposomes in pharmacotherapeutics including in diagnostics, brain targeting, eye and cancer diseases, and in infections are provided. The experimental approaches that may reduce, or even bypass, the use of liposomal drug drawbacks is described. The application of liposomes in the treatment of numerous diseases is discussed.
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Affiliation(s)
| | - Abdelwahab Omri
- Department of Chemistry and Biochemistry, The Novel Drug and Vaccine Delivery Systems Facility, Laurentian University, Sudbury, ON P3E 2C6, Canada
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9
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Rauf A, Abu-Izneid T, Khalil AA, Hafeez N, Olatunde A, Rahman M, Semwal P, Al-Awthan YS, Bahattab OS, Khan IN, Khan MA, Sharma R. Nanoparticles in clinical trials of COVID-19: An update. Int J Surg 2022; 104:106818. [PMID: 35953020 PMCID: PMC9359769 DOI: 10.1016/j.ijsu.2022.106818] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 07/30/2022] [Accepted: 07/31/2022] [Indexed: 11/01/2022]
Abstract
Once the World Health Organization (WHO) declared the COVID-19 (Coronavirus Infectious Disease-19) outbreak to be pandemic, massive efforts have been launched by researchers around the globe to combat this emerging infectious disease. Strategies that must be investigated such as expanding testing capabilities, developing effective medicines, as well as developing safe and effective vaccines for COVID-19 disease that produce long-lasting immunity to human system. Now-a-days, bio-sensing, medication delivery, imaging, and antimicrobial treatment are just a few of the medical applications for nanoparticles (NPs). Since the early 1990s, nanoparticle drug delivery methods have been employed in clinical trials. Since then, the discipline of nanomedicine has evolved in tandem with expanding technological demands to better medicinal delivery. Newer generations of NPs have emerged in recent decades that are capable of performing additional delivery tasks, allowing for therapy via novel therapeutic modalities. Many of these next generation NPs and associated products have entered clinical trials and have been approved for diverse indications in the present clinical environment. For systemic applications, NPs or nanomedicine-based drug delivery systems have substantial benefits over their non-formulated and free drug counterparts. Nanoparticle systems, for example, are capable of delivering medicines and treating parts of the body that are inaccessible to existing delivery systems. As a result, NPs medication delivery is one of the most studied preclinical and clinical systems. NPs-based vaccines delivering SARS-CoV-2 antigens will play an increasingly important role in prolonging or improving COVID-19 vaccination outcomes. This review provides insights about employing NPs-based drug delivery systems for the treatment of COVID-19 to increase the bioavailability of current drugs, reducing their toxicity, and to increase their efficiency. This article also exhibits their capability and efficacy, and highlighting the future aspects and challenges on nanoparticle products in clinical trials of COVID-19.
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Affiliation(s)
- Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, 23430, Khyber Pakhtunkhwa (KP), Pakistan.
| | - Tareq Abu-Izneid
- Pharmaceutical Sciences Department, College of Pharmacy, Al Ain University for Science and Technology, Al Ain, United Arab Emirates
| | - Anees Ahmed Khalil
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, 54000, Pakistan
| | - Nabia Hafeez
- Center of Biotechnology and Microbiology, University of Peshawar, Peshawar-KPK, 25120, KPK, Pakistan
| | - Ahmed Olatunde
- Department of Medical Biochemistry, Abubakar Tafawa Balewa University, Bauchi, 740272, Nigeria
| | - Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, 1207 Dhaka, Bangladesh
| | - Prabhakar Semwal
- Department of Life Sciences, Graphic Era Deemed to be University, Dehradun, 248002, Uttarakhand, India
| | | | - Omar Salem Bahattab
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Ishaq N Khan
- Institute of Basic Medical Sciences Khyber Medical University, Peshawar, 25100, Pakistan
| | - Muhammad Arslan Khan
- Department of Pharmacy, Faculty of Pharmacy, The University of Lahore, 54000, Pakistan
| | - Rohit Sharma
- Department of Rasa Shastra &Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
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Cai D, Gao W, Li Z, Zhang Y, Xiao L, Xiao Y. Current Development of Nano-Drug Delivery to Target Macrophages. Biomedicines 2022; 10:1203. [PMID: 35625939 PMCID: PMC9139084 DOI: 10.3390/biomedicines10051203] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/16/2022] [Accepted: 05/18/2022] [Indexed: 11/16/2022] Open
Abstract
Macrophages are the most important innate immune cells that participate in various inflammation-related diseases. Therefore, macrophage-related pathological processes are essential targets in the diagnosis and treatment of diseases. Since nanoparticles (NPs) can be preferentially taken up by macrophages, NPs have attracted most attention for specific macrophage-targeting. In this review, the interactions between NPs and the immune system are introduced to help understand the pharmacokinetics and biodistribution of NPs in immune cells. The current design and strategy of NPs modification for specific macrophage-targeting are investigated and summarized.
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Affiliation(s)
- Donglin Cai
- Centre for Biomedical Technologies, School of Mechanical, Medical & Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; (D.C.); (W.G.); (Z.L.)
- State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China;
| | - Wendong Gao
- Centre for Biomedical Technologies, School of Mechanical, Medical & Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; (D.C.); (W.G.); (Z.L.)
| | - Zhelun Li
- Centre for Biomedical Technologies, School of Mechanical, Medical & Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; (D.C.); (W.G.); (Z.L.)
- State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China;
| | - Yufeng Zhang
- State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China;
| | - Lan Xiao
- Centre for Biomedical Technologies, School of Mechanical, Medical & Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; (D.C.); (W.G.); (Z.L.)
- Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Brisbane, QLD 4059, Australia
| | - Yin Xiao
- Centre for Biomedical Technologies, School of Mechanical, Medical & Process Engineering, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia; (D.C.); (W.G.); (Z.L.)
- Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Brisbane, QLD 4059, Australia
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11
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Hou Z, Liu J, Jin Z, Qiu G, Xie Q, Mi S, Huang J. Use of chemotherapy to treat hepatocellular carcinoma. Biosci Trends 2022; 16:31-45. [PMID: 35173139 DOI: 10.5582/bst.2022.01044] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatic malignancies remain a global challenge. Hepatocellular carcinoma (HCC) accounts for around 90% of patients with liver cancer and is the sixth most common neoplasm worldwide and the fourth leading cause of cancer-related death. However, the long-term prognosis for HCC remains far from satisfactory, with a late diagnosis and limited treatment. DOX has served as conventional chemotherapy with the longest history of use. Although conventional chemotherapy is being challenged by molecular therapy and immune therapy, there is renewed optimism and interest in both systematic and locoregional therapy. Combined chemotherapy is widely used in clinical practice. In specific terms, FOLFOX can serve as a first-line (category 2B) option as recommended by the 2021 NCCN guidelines, while the efficacy of LTLD plus RFA has been confirmed in the phase III HEAT study. These approaches have challenged the dominant status of molecular therapy in terms of health economics and they have potential benefits in Asia, where HBV-related hepatocellular carcinoma is prevalent. Moreover, locoregional chemotherapy can be achieved with TACE and HAIC (possibly involving FOLFOX, DOX, mitomycin C, cisplatin, epirubicin, etc.). TACE was officially recommended by the 2021 NCCN guidelines for patients with Child-Pugh class B liver disease. In addition, HAIC has demonstrated a potential advantage in preliminary clinical practice, although it hasn't been included in any guidelines. Hence, this review summarizes large-scale trials and studies examining the development and innovative use of chemotherapeutic agents. Mounting clinical evidence warrants an exploration of the efficacy of chemotherapy.
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Affiliation(s)
- Ziqi Hou
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Liu
- Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhaoxing Jin
- Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
| | - Guoteng Qiu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Qingyun Xie
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Shizheng Mi
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jiwei Huang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
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12
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Mei L, Chen B, Fan R, Wu M, Weng C, Tong A, Zou B, Yang H, Nie C, Guo G. Magic of Architecting Oligo‐DNAs: 3D Structure‐Dependent Stability and Programmable Specificity to Tumor Cells. ADVANCED FUNCTIONAL MATERIALS 2022. [DOI: 10.1002/adfm.202112544] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Lan Mei
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Bo Chen
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Rangrang Fan
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Min Wu
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Chengxin Weng
- Department of Vascular Surgery West China Hospital Sichuan University Chengdu 610041 China
| | - Aiping Tong
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Bingwen Zou
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Hui Yang
- Department of Otorhiolaryngology Head and Neck Surgery West China Hospital Sichuan University Chengdu 610041 China
| | - Chunlai Nie
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
| | - Gang Guo
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Collaborative Innovation Center for Biotherapy Chengdu 610041 China
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Borys N, Dewhirst MW. Drug development of lyso-thermosensitive liposomal doxorubicin: Combining hyperthermia and thermosensitive drug delivery. Adv Drug Deliv Rev 2021; 178:113985. [PMID: 34555486 DOI: 10.1016/j.addr.2021.113985] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 11/13/2020] [Accepted: 09/16/2021] [Indexed: 11/24/2022]
Abstract
We review the drug development of lyso-thermosensitive liposomal doxorubicin (LTLD) which is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. This class of compounds is designed to carry a payload of a cytotoxic agent and adequately circulate in order to accumulate at a tumor that is being heated. At the target the carrier is activated by heat and releases its contents at high concentrations. We summarize the preclinical and clinical experience of LTLD including its successes and challenges in the development process.
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Rommasi F, Esfandiari N. Liposomal Nanomedicine: Applications for Drug Delivery in Cancer Therapy. NANOSCALE RESEARCH LETTERS 2021; 16:95. [PMID: 34032937 PMCID: PMC8149564 DOI: 10.1186/s11671-021-03553-8] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 05/17/2021] [Indexed: 05/23/2023]
Abstract
The increasing prevalence of cancer, a disease in which rapid and uncontrollable cell growth causes complication and tissue dysfunction, is one of the serious and tense concerns of scientists and physicians. Nowadays, cancer diagnosis and especially its effective treatment have been considered as one of the biggest challenges in health and medicine in the last century. Despite significant advances in drug discovery and delivery, their many adverse effects and inadequate specificity and sensitivity, which usually cause damage to healthy tissues and organs, have been great barriers in using them. Limitation in the duration and amount of these therapeutic agents' administration is also challenging. On the other hand, the incidence of tumor cells that are resistant to typical methods of cancer treatment, such as chemotherapy and radiotherapy, highlights the intense need for innovation, improvement, and development in antitumor drug properties. Liposomes have been suggested as a suitable candidate for drug delivery and cancer treatment in nanomedicine due to their ability to store drugs with different physical and chemical characteristics. Moreover, the high flexibility and potential of liposome structure for chemical modification by conjugating various polymers, ligands, and molecules is a significant pro for liposomes not only to enhance their pharmacological merits but also to improve the effectiveness of anticancer drugs. Liposomes can increase the sensitivity, specificity, and durability of these anti-malignant cell agents in the body and provide remarkable benefits to be applied in nanomedicines. We reviewed the discovery and development of liposomes focusing on their clinical applications to treat diverse sorts of cancers and diseases. How the properties of liposomal drugs can be improved and their opportunity and challenges for cancer therapy were also considered and discussed.
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Affiliation(s)
- Foad Rommasi
- Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Neda Esfandiari
- Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
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15
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Almalki M, Lai EP, Ko R, Li C. Facile preparation of liposome-encapsulated Zn–DTPA from soy lecithin for decorporation of radioactive actinides. CAN J CHEM 2021. [DOI: 10.1139/cjc-2020-0340] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Diethylenetriaminepentaacetic acid (DTPA) is an attractive decorporation agent that can enhance the excretion of radioactive actinides such as plutonium, americium, and curium after a radiological incident. However, DTPA is excreted in a short period of time after administration. Several formulations have been developed to improve DTPA pharmacokinetics properties. In this project, liposomes were prepared facilely from soy lecithin as a nanocarrier for pulmonary delivery of Zn–DTPA. Lipid hydration, reverse phase evaporation, and mechanical sonication were three methods evaluated for the preparation of liposome-encapsulated Zn-DTPA (lipo-Zn-DTPA). Mechanical sonication was the method of choice due to simple apparatus and facile preparation. Lipo-Zn–DTPA exhibited a hydrodynamic diameter of 178 ± 2 nm and a spherical shape. The loading capacity and encapsulation efficiency of Zn–DTPA were 41 ± 5 mg/g and 10% ± 1%, respectively. Lyophilization of lipo-Zn–DTPA for extended storage did not affect the amount of encapsulated drug or damage the structure of liposomes. An in vivo cytotoxicity test confirmed no serious adverse effect of Zn–DTPA encapsulated lecithin liposomes in rats.
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Affiliation(s)
- Manal Almalki
- Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada
| | - Edward P.C. Lai
- Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada
| | - Raymond Ko
- Radiation Protection Bureau, Health Canada, Ottawa, ON K1A 1C1, Canada
| | - Chunsheng Li
- Radiation Protection Bureau, Health Canada, Ottawa, ON K1A 1C1, Canada
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16
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Park J, Lee YK, Park IK, Hwang SR. Current Limitations and Recent Progress in Nanomedicine for Clinically Available Photodynamic Therapy. Biomedicines 2021; 9:85. [PMID: 33467201 PMCID: PMC7830249 DOI: 10.3390/biomedicines9010085] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/12/2021] [Accepted: 01/13/2021] [Indexed: 02/07/2023] Open
Abstract
Photodynamic therapy (PDT) using oxygen, light, and photosensitizers has been receiving great attention, because it has potential for making up for the weakness of the existing therapies such as surgery, radiation therapy, and chemotherapy. It has been mainly used to treat cancer, and clinical tests for second-generation photosensitizers with improved physicochemical properties, pharmacokinetic profiles, or singlet oxygen quantum yield have been conducted. Progress is also being made in cancer theranostics by using fluorescent signals generated by photosensitizers. In order to obtain the effective cytotoxic effects on the target cells and prevent off-target side effects, photosensitizers need to be localized to the target tissue. The use of nanocarriers combined with photosensitizers can enhance accumulation of photosensitizers in the tumor site, owing to preferential extravasation of nanoparticles into the tumor vasculature by the enhanced permeability and retention effect. Self-assembly of amphiphilic polymers provide good loading efficiency and sustained release of hydrophobic photosensitizers. In addition, prodrug nanomedicines for PDT can be activated by stimuli in the tumor site. In this review, we introduce current limitations and recent progress in nanomedicine for PDT and discuss the expected future direction of research.
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Affiliation(s)
- Jooho Park
- Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Korea;
| | - Yong-Kyu Lee
- Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Korea;
| | - In-Kyu Park
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Korea;
| | - Seung Rim Hwang
- College of Pharmacy, Chosun University, Gwangju 61452, Korea
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Price LSL, Stern ST, Deal AM, Kabanov AV, Zamboni WC. A reanalysis of nanoparticle tumor delivery using classical pharmacokinetic metrics. SCIENCE ADVANCES 2020; 6:eaay9249. [PMID: 32832614 PMCID: PMC7439617 DOI: 10.1126/sciadv.aay9249] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 05/29/2020] [Indexed: 05/15/2023]
Abstract
Nanoparticle (NP) delivery to solid tumors has recently been questioned. To better understand the magnitude of NP tumor delivery, we reanalyzed published murine NP tumor pharmacokinetic (PK) data used in the Wilhelm et al. study. Studies included in their analysis reporting matched tumor and blood concentration versus time data were evaluated using classical PK endpoints and compared to the unestablished percent injected dose (%ID) in tumor metric from the Wilhelm et al. study. The %ID in tumor was poorly correlated with standard PK metrics that describe NP tumor delivery (AUCtumor/AUCblood ratio) and only moderately associated with maximal tumor concentration. The relative tumor delivery of NPs was ~100-fold greater as assessed by the standard AUCtumor/AUCblood ratio than by %ID in tumor. These results strongly suggest that PK metrics and calculations can influence the interpretation of NP tumor delivery and stress the need to properly validate novel PK metrics against traditional approaches.
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Affiliation(s)
- Lauren S. L. Price
- Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), University of North Carolina, Chapel Hill, NC, USA
- Translational Oncology and Nanoparticle Drug Development (TOND2I) Lab, University of North Carolina, Chapel Hill, NC, USA
| | - Stephan T. Stern
- Nanotechnology Characterization Lab (NCL), Frederick National Laboratory for Cancer Research, Frederick, MD, USA
| | - Allison M. Deal
- UNC Lineberger Biostatistics Shared Resource, Chapel Hill, NC, USA
| | - Alexander V. Kabanov
- Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), University of North Carolina, Chapel Hill, NC, USA
- UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA
- Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA
- Carolina Institute for Nanomedicine, University of North Carolina, Chapel Hill, NC, USA
| | - William C. Zamboni
- Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), University of North Carolina, Chapel Hill, NC, USA
- Translational Oncology and Nanoparticle Drug Development (TOND2I) Lab, University of North Carolina, Chapel Hill, NC, USA
- UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA
- Center for Nanotechnology in Drug Delivery, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA
- Carolina Institute for Nanomedicine, University of North Carolina, Chapel Hill, NC, USA
- Corresponding author.
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Yan L, Shen J, Wang J, Yang X, Dong S, Lu S. Nanoparticle-Based Drug Delivery System: A Patient-Friendly Chemotherapy for Oncology. Dose Response 2020; 18:1559325820936161. [PMID: 32699536 PMCID: PMC7357073 DOI: 10.1177/1559325820936161] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/11/2020] [Accepted: 05/27/2020] [Indexed: 12/24/2022] Open
Abstract
Chemotherapy is widely used to treat cancer. The toxic effect of conventional chemotherapeutic drugs on healthy cells leads to serious toxic and side effects of conventional chemotherapy. The application of nanotechnology in tumor chemotherapy can increase the specificity of anticancer agents, increase the killing effect of tumors, and reduce toxic and side effects. Currently, a variety of formulations based on nanoparticles (NPs) for delivering chemotherapeutic drugs have been put into clinical use, and several others are in the stage of development or clinical trials. In this review, after briefly introducing current cancer chemotherapeutic methods and their limitations, we describe the clinical applications and advantages and disadvantages of several different types of NPs-based chemotherapeutic agents. We have summarized a lot of information in tables and figures related to the delivery of chemotherapeutic drugs based on NPs and the design of NPs with active targeting capabilities.
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Affiliation(s)
- Lina Yan
- Department of Rehabilitation Medicine, The First People’s Hospital of Wenling, Wenzhou Medical University, Wenling, Zhejiang, China
| | - Jingjing Shen
- School of Civil Engineering and Architecture, Taizhou University, Taizhou, Zhejiang, China
| | - Jinqiao Wang
- Department of Rehabilitation Medicine, The First People’s Hospital of Wenling, Wenzhou Medical University, Wenling, Zhejiang, China
| | - Xiaoyan Yang
- Department of Rehabilitation Medicine, The First People’s Hospital of Wenling, Wenzhou Medical University, Wenling, Zhejiang, China
| | - Shiyan Dong
- School of Life Sciences, Jilin University, Changchun, Jilin, China
| | - Saijun Lu
- Department of Rehabilitation Medicine, The First People’s Hospital of Wenling, Wenzhou Medical University, Wenling, Zhejiang, China
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Mousa DS, El-Far AH, Saddiq AA, Sudha T, Mousa SA. Nanoformulated Bioactive Compounds Derived from Different Natural Products Combat Pancreatic Cancer Cell Proliferation. Int J Nanomedicine 2020; 15:2259-2268. [PMID: 32280218 PMCID: PMC7127850 DOI: 10.2147/ijn.s238256] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 02/26/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose This study was designed to determine the potential effect of nanoencapsulated bioactive compounds from different natural sources on human pancreatic cancer. Background Pancreatic cancer carries the highest fatality rate among all human cancers because of its high metastatic potential and late presentation at the time of diagnosis. Hence there is a need for improved methods to prevent and treat it. Natural products, such as 3, 3′-diindolylmethane (DIM) and ellagic acid (EA) demonstrated anticancer efficacy against various cancer types. However, DIM is insoluble. Hence, using nanotechnology to encapsulate these compounds in combination with EA might improve their physical and chemical properties and their delivery to the cancer cells. Methods Human pancreatic cancer cells, namely SUIT2-luciferase transfected, were used to examine the effects of DIM or EA and their nanoformulation in poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) [PLGA-PEG] nanoparticles (NPs) on SUIT2-luciferase cell viability/proliferation over 24 hrs. Additionally, effects on tumor weight and angiogenesis were determined using the chick chorioallantoic membrane (CAM) tumor implant model. Results Both DIM and EA PLGA-PEG NPs resulted in rapid suppression of pancreatic cancer cell viability/proliferation within 24 hrs (P < 0.01), while the non-encapsulated DIM and EA did not show any significant effect on SUIT2 cancer cell viability or cell proliferation (MTT assay). In the CAM pancreatic cancer cell (SUIT2) implant model, results showed a greater suppression of tumor weight (P < 0.01), tumor cell viability, and tumor angiogenesis (P < 0.01) for DIM NPs and EA NPs and their combinations versus DIM or EA alone. Conclusion Nanoformulation of DIM and EA resulted in a more effective suppression of pancreatic cancer cell viability, pancreatic tumor weight, implanted cancer cell viability, and tumor angiogenesis as compared with these bioactive compounds alone.
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Affiliation(s)
| | - Ali H El-Far
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
| | - Amna A Saddiq
- Faculty of Science, Department of Biology, University of Jeddah, Jeddah 21589, Saudi Arabia
| | - Thangirala Sudha
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
| | - Shaker A Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
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20
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Bibi N, Awan IT, Awan AT. New Adsorption-Based Biosensors for Cancer Detections and Role of Nano-medicine in Its Prognosis and Inhibition. 'ESSENTIALS OF CANCER GENOMIC, COMPUTATIONAL APPROACHES AND PRECISION MEDICINE 2020:107-140. [DOI: 10.1007/978-981-15-1067-0_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Kuznetsova DA, Gaynanova GA, Vasileva LA, Sibgatullina GV, Samigullin DV, Sapunova AS, Voloshina AD, Galkina IV, Petrov KA, Zakharova LY. Mitochondria-targeted cationic liposomes modified with alkyltriphenylphosphonium bromides loaded with hydrophilic drugs: preparation, cytotoxicity and colocalization assay. J Mater Chem B 2019; 7:7351-7362. [PMID: 31696196 DOI: 10.1039/c9tb01853k] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The purpose of this work was to obtain cationic liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine noncovalently modified using alkyltriphenylphosphonium bromides (TPPB-n) with different lengths of hydrocarbon tail for targeted delivery to mitochondria. The hydrodynamic diameter and electrokinetic potential of hybrid liposomes depending on the lipid/surfactant ratio were monitored in time with the aim to optimize the composition with sufficient stability and positive charge for mitochondria-targeted delivery. It was found that increasing the alkyl tail length of the surfactant (up to TPPB-14) leads to an increase in the positive charge of the liposomes. The most optimal results of stability were obtained for hybrid liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and TPPB-12, TPPB-14. The obtained modified liposomes were loaded with hydrophilic substrates (a model probe Rhodamine B and medicines metronidazole and doxorubicin). This is one of the first examples of fabrication of liposomes noncovalently modified using an amphiphilic TPP cation, with the alkyl tail length of surfactant and TPP/lipid ratio optimized in terms of stability of the liposomes and the binding/release behavior of hydrophilic probes. Using the confocal microscopy method, it was shown that modification of liposomes with a triphenylphosphonium cation results in targeted delivery of encapsulated compounds to mitochondria.
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Affiliation(s)
- Darya A Kuznetsova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation.
| | - Gulnara A Gaynanova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation.
| | - Leysan A Vasileva
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation. and Kazan National Research Technological University, 68 Karl Marx str., Kazan, 420015, Russian Federation
| | - Guzel V Sibgatullina
- Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevski str., Kazan, 420111, Russian Federation
| | - Dmitry V Samigullin
- Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevski str., Kazan, 420111, Russian Federation
| | - Anastasiia S Sapunova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation.
| | - Alexandra D Voloshina
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation.
| | - Irina V Galkina
- Kazan Federal University, 18 Kremlyovskaya str., Kazan, 420008, Russian Federation
| | - Konstantin A Petrov
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation. and Kazan Federal University, 18 Kremlyovskaya str., Kazan, 420008, Russian Federation
| | - Lucia Ya Zakharova
- Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, 8 Arbuzov str., Kazan, 420088, Russian Federation.
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Inchingolo R, Posa A, Mariappan M, Spiliopoulos S. Locoregional treatments for hepatocellular carcinoma: Current evidence and future directions. World J Gastroenterol 2019; 25:4614-4628. [PMID: 31528090 PMCID: PMC6718039 DOI: 10.3748/wjg.v25.i32.4614] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Liver cancers are the second most frequent cause of global cancer-related mortality of which 90% are attributable to hepatocellular carcinoma (HCC). Despite the advent of screening programmes for patients with known risk factors, a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy. This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization, radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant. The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.
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Affiliation(s)
- Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
- Department of Radiology, King´s College Hospital, London SE5 9RS, United Kingdom
| | - Alessandro Posa
- Department of Radiology, IRCSS Fatebenefratelli Hospital, Roma 00186, Italy
| | - Martin Mariappan
- Interventional Radiology Department, Aberdeen Royal Infirmary Hospital, Aberdeen AB25 2ZN, United Kingdom
| | - Stavros Spiliopoulos
- 2nd Radiology Department, School of Medicine; National and Kapodistrian University of Athens, Chaidari Athens 12461, Greece
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Fahmy HM. In vitro study of the cytotoxicity of thymoquinone/curcumin fluorescent liposomes. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:1465-1476. [PMID: 31377882 DOI: 10.1007/s00210-019-01688-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 06/28/2019] [Indexed: 01/14/2023]
Abstract
In the present study, thymoquinone-loaded liposomes (Lip (TQ)), curcumin-encapsulated liposome (Lip (CUR)), and thymoquinone/curcumin-encapsulated liposome (Lip (TQ + CUR)) in addition to rhodamine-labeled thymoquinone/curcumin liposome (Lip (TQ + CUR + ROD)) were prepared with encapsulation efficiency exceeding 99%. The aim of the present study was to evaluate the effect of the different prepared formulations either labeled with the fluorescent dye (rhodamine B) or not on A549 lung cancer cells. Cytotoxicity of different formulations was assessed by MTT assay. Proliferation of A549 cells was significantly inhibited by the different formulations in a concentration-dependent manner in 72 h. The Lip (TQ + CUR + ROD) formulation demonstrated the lowest IC50 value. To investigate its mechanism of action on A549 lung cancer cells, the Comet assay (for DNA damage) was done, the measurement of some oxidative stress parameters in addition to performing inverted fluorescence microscopy imaging. The results of the present study demonstrated the increased DNA damage, oxidative stress damage, and cell apoptosis in A549 treated with TQ, CUR, and rhodamine-encapsulated fluorescent liposome formulation as compared to untreated cells. The results obtained from the present study demonstrate the significant role of the TQ/CUR fluorescent liposomes on decreasing the viability of A549 lung cancer cells. Graphical abstract.
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Affiliation(s)
- Heba Mohamed Fahmy
- Biophysics Department, Faculty of Science, Cairo University, 16 El Zafer Street, Haram, Giza, Egypt.
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25
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Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients. Cancer Chemother Pharmacol 2018; 83:61-70. [PMID: 30327876 DOI: 10.1007/s00280-018-3702-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 10/10/2018] [Indexed: 10/28/2022]
Abstract
PURPOSE Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. METHODS Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. RESULTS Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67-28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = - 0.75 and - 0.76, respectively, p = 0.02 for both). CONCLUSIONS Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients.
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El-Far AH, Al Jaouni SK, Li W, Mousa SA. Protective Roles of Thymoquinone Nanoformulations: Potential Nanonutraceuticals in Human Diseases. Nutrients 2018; 10:E1369. [PMID: 30257423 PMCID: PMC6213571 DOI: 10.3390/nu10101369] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 09/17/2018] [Accepted: 09/18/2018] [Indexed: 01/07/2023] Open
Abstract
The focus on nanotechnology for improved bioavailability and drug delivery is of increasing importance for control of different human diseases. Therefore, numerous nanoformulations have been developed for the oral bioavailability of different drugs. This review introduces applications of nanomedicine to enhance the biological activities of thymoquinone (TQ) to control different diseases in several in vivo studies as a preliminary investigation for human disease treatment with nano-TQ. Nano-TQ effectively augments the anticancer roles of doxorubicin by upregulation of P53 and downregulation of Bcl2 and potentiates paclitaxel's apoptosis in MCF-7 breast cancer cells. Moreover, nano-TQ protects against diabetes, inflammation, CNS, and hepatotoxicity, mainly by enhancement of organs' antioxidant status. We summarize the pros and cons of several FDA approved nanoparticle-based therapeutics and discuss the roadblocks in clinical translation, along with potential nano-TQ strategies to overcome these roadblocks. From this review, we can conclude that nano-TQ may be considered as a promising nutraceutical for human health.
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Affiliation(s)
- Ali H El-Far
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.
| | - Soad K Al Jaouni
- Department of Hematology/Pediatric Oncology, Faculty of Medicine, King Abdulaziz University, Yousef Abdulatif Jameel scientific chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
| | - Weikun Li
- The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
| | - Shaker A Mousa
- The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA.
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27
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Schorzman AN, Lucas AT, Kagel JR, Zamboni WC. Methods and Study Designs for Characterizing the Pharmacokinetics and Pharmacodynamics of Carrier-Mediated Agents. Methods Mol Biol 2018; 1831:201-228. [PMID: 30051434 DOI: 10.1007/978-1-4939-8661-3_15] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Major advances in carrier-mediated agents (CMAs), which include nanoparticles, nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages, such as greater solubility, duration of exposure, and delivery to the site of action over their small molecule counterparts, there is substantial variability in systemic clearance and distribution, tumor delivery, and pharmacologic effects (efficacy and toxicity) of these agents. In this chapter, we focus on the analytical and phenotypic methods required to design a study that characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of all forms of these nanoparticle-based drug agents. These methods include separation of encapsulated and released drugs, ultrafiltration for measurement of non-protein bound active drug, microdialysis to measure intra-tumor drug concentrations, immunomagnetic separation and flow cytometry for sorting cell types, and evaluation of spatial distribution of drug forms relative to tissue architecture by mass spectrometry imaging and immunohistochemistry.
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Affiliation(s)
- Allison N Schorzman
- Translational Oncology and Nanoparticle Drug Development Initiative (TOND2I) Lab, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Andrew T Lucas
- Translational Oncology and Nanoparticle Drug Development Initiative (TOND2I) Lab, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - John R Kagel
- Translational Oncology and Nanoparticle Drug Development Initiative (TOND2I) Lab, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - William C Zamboni
- Translational Oncology and Nanoparticle Drug Development Initiative (TOND2I) Lab, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Su H, Wang Y, Gu Y, Bowman L, Zhao J, Ding M. Potential applications and human biosafety of nanomaterials used in nanomedicine. J Appl Toxicol 2018; 38:3-24. [PMID: 28589558 PMCID: PMC6506719 DOI: 10.1002/jat.3476] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Revised: 03/21/2017] [Accepted: 03/21/2017] [Indexed: 12/18/2022]
Abstract
With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research. Copyright © 2017 John Wiley & Sons, Ltd.
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Affiliation(s)
- Hong Su
- Department of Preventative Medicine, Zhejiang Provincial
Key Laboratory of Pathological and Physiological Technology, School of Medicine,
Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang Province 315211,
People’s Republic of China
| | - Yafei Wang
- Department of Preventative Medicine, Zhejiang Provincial
Key Laboratory of Pathological and Physiological Technology, School of Medicine,
Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang Province 315211,
People’s Republic of China
| | - Yuanliang Gu
- Department of Preventative Medicine, Zhejiang Provincial
Key Laboratory of Pathological and Physiological Technology, School of Medicine,
Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang Province 315211,
People’s Republic of China
| | - Linda Bowman
- Toxicology and Molecular Biology Branch, Health Effects
Laboratory Division, National Institute for Occupational Safety and Health,
Morgantown, WV, 26505, USA
| | - Jinshun Zhao
- Department of Preventative Medicine, Zhejiang Provincial
Key Laboratory of Pathological and Physiological Technology, School of Medicine,
Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang Province 315211,
People’s Republic of China
- Toxicology and Molecular Biology Branch, Health Effects
Laboratory Division, National Institute for Occupational Safety and Health,
Morgantown, WV, 26505, USA
| | - Min Ding
- Toxicology and Molecular Biology Branch, Health Effects
Laboratory Division, National Institute for Occupational Safety and Health,
Morgantown, WV, 26505, USA
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Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice. Antimicrob Agents Chemother 2017; 61:AAC.00962-17. [PMID: 28827416 DOI: 10.1128/aac.00962-17] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 08/11/2017] [Indexed: 01/05/2023] Open
Abstract
Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.
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Tak WY, Lin SM, Wang Y, Zheng J, Vecchione A, Park SY, Chen MH, Wong S, Xu R, Peng CY, Chiou YY, Huang GT, Cai J, Abdullah BJJ, Lee JS, Lee JY, Choi JY, Gopez-Cervantes J, Sherman M, Finn RS, Omata M, O'Neal M, Makris L, Borys N, Poon R, Lencioni R. Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions. Clin Cancer Res 2017; 24:73-83. [PMID: 29018051 DOI: 10.1158/1078-0432.ccr-16-2433] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 02/17/2017] [Accepted: 10/05/2017] [Indexed: 12/17/2022]
Abstract
Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.
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Affiliation(s)
- Won Young Tak
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
| | - Shi-Ming Lin
- Chang Gung Memorial Hospital - Linkou, Taoyuan, Taiwan
| | - Yijun Wang
- Third Central Hospital of Tianjin, Tianjin, China
| | - Jiasheng Zheng
- Beijing You'an Hospital, Capital Medical University, Beijing, China
| | | | - Soo Young Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Min Hua Chen
- Peking University Cancer Hospital, Department of Ultrasound, Beijing, China
| | | | - Ruocai Xu
- Hunan Cancer Hospital, Department of Hepatobiliary and Pancreatic Internal Medicine, Changsha, China
| | | | - Yi-You Chiou
- Taipei Veterans General Hospital, Taipei, Taiwan
| | | | - Jianqiang Cai
- Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China
| | | | - June Sung Lee
- Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Jae Young Lee
- Seoul National University Hospital, Seoul, Republic of Korea
| | | | | | | | - Richard S Finn
- Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, California
| | - Masao Omata
- Yamanashi Prefectural Central Hospital, Yamanashi, Japan
| | | | | | | | - Ronnie Poon
- Queen Mary Hospital, University of Hong Kong, Hong Kong, China
| | - Riccardo Lencioni
- University of Miami Miller School of Medicine, Section of Vascular and Interventional Radiology, Sylvester Comprehensive Cancer Center, Miami, Florida
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31
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Madden AJ, Oberhardt B, Lockney D, Santos C, Vennam P, Arney D, Franzen S, Lommel SA, Miller CR, Gehrig P, Zamboni WC. Pharmacokinetics and efficacy of doxorubicin-loaded plant virus nanoparticles in preclinical models of cancer. Nanomedicine (Lond) 2017; 12:2519-2532. [PMID: 28952882 DOI: 10.2217/nnm-2016-0421] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
AIM To compare the pharmacokinetics and efficacy of doxorubicin containing plant virus nanoparticles (PVNs) with PEGylated liposomal doxorubicin (PLD) and small molecule doxorubicin in two mouse models of cancer. MATERIALS & METHODS Studies were performed in A375 melanoma and intraperitoneal SKOV3ip1 ovarian cancer xenografts. The PVNs were administered in lower and more frequent doses in the ovarian model. RESULTS The PVNs were more efficacious than PLD and small molecule doxorubicin in the ovarian cancer model, but not in the melanoma cancer model. The pharmacokinetics profiles of the PVNs showed fast plasma clearance, but more efficient tumor delivery as compared with other carrier-mediated agents. CONCLUSION PVNs administered at lower repeated doses provide both pharmacologic and efficacy advantages compared with PLD.
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Affiliation(s)
- Andrew J Madden
- Division of Pharmacotherapy & Experimental Therapeutics, University of North Carolina at Chapel Hill (UNC) Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | | | | | - Charlene Santos
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | | | | | - Stefan Franzen
- Nanovector Inc., Raleigh, NC, USA.,Department of Chemistry, North Carolina State University, Raleigh, NC, USA
| | - Steven A Lommel
- Nanovector Inc., Raleigh, NC, USA.,Department of Plant Pathology, North Carolina State University, Raleigh, NC, USA
| | - C Ryan Miller
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.,Department of Pathology & Laboratory Medicine, UNC at Chapel Hill, Chapel Hill, NC, USA
| | - Paola Gehrig
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.,Department of Obstetrics & Gynecology, Division of Gynecology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - William C Zamboni
- Division of Pharmacotherapy & Experimental Therapeutics, University of North Carolina at Chapel Hill (UNC) Eshelman School of Pharmacy, Chapel Hill, NC, USA.,Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.,Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina, Chapel Hill, NC, USA
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32
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Lucas AT, Price LS, Schorzman A, Zamboni WC. Complex effects of tumor microenvironment on the tumor disposition of carrier-mediated agents. Nanomedicine (Lond) 2017; 12:2021-2042. [PMID: 28745129 DOI: 10.2217/nnm-2017-0101] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Major advances in carrier-mediated agents, including nanoparticle, conjugates and antibody-drug conjugates, have created revolutionary drug delivery systems in cancer over the past two decades. While these agents provide several advantages, such as greater duration of exposure and solubility, compared with their small-molecule counterparts, there is substantial variability in delivery of these agents to tissues and especially tumors. This review provides an overview of tumor microenvironment factors that affect the pharmacokinetics and pharmacodynamics of carrier-mediated agents observed in preclinical models and patients.
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Affiliation(s)
- Andrew T Lucas
- Division of Pharmacotherapy & Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Lauren Sl Price
- Division of Pharmacotherapy & Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Allison Schorzman
- Division of Pharmacotherapy & Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - William C Zamboni
- Division of Pharmacotherapy & Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.,Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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33
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Ferguson EL, Scomparin A, Hailu H, Satchi-Fainaro R. HPMA copolymer-phospholipase C and dextrin-phospholipase A2 as model triggers for polymer enzyme liposome therapy (PELT). J Drug Target 2017; 25:818-828. [PMID: 28728446 DOI: 10.1080/1061186x.2017.1358726] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
'Polymer Enzyme Liposome Therapy' (PELT) is a two-step anticancer approach in which a liposomal drug and polymer-phospholipase conjugate are administered sequentially to target the tumour interstitium by the enhanced permeability and retention effect, and trigger rapid, local, drug release. To date, however, the concept has only been described theoretically. We synthesised two polymer conjugates of phospholipase C (PLC) and A2 (PLA2) and evaluated their ability to trigger anthracycline release from the clinically used liposomes, Caelyx® and DaunoXome®. N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-PLC and a dextrin-PLA2 were synthesised and their enzymatic activity characterised. Doxorubicin release from polyethyleneglycol-coated (PEGylated) Caelyx® was relatively slow (<20%, 60 min), whereas daunomycin was rapidly released from non-PEGylated DaunoXome® (∼87%) by both enzymes. Incubation with dextrin-PLA2 triggered significantly less daunomycin release than HPMA copolymer-PLC, but when dextrin-PLA2 was pre-incubated with α-amylase, the rate of daunomycin release increased. DaunoXome®'s diameter increased in the presence of PLA2, while Caelyx®'s diameter was unaffected by free or conjugated PLA2. Dextrin-PLA2 potentiated the cytotoxicity of DaunoXome® to MCF-7 cells to a greater extent than free PLA2, while combining dextrin-PLA2 with Caelyx® resulted in antagonism, even in the presence of α-amylase, presumably due to steric hindrance by PEG. Our findings suggest that in vivo studies to evaluate PELT combinations should be further evaluated.
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Affiliation(s)
- Elaine L Ferguson
- a Centre for Polymer Therapeutics, Welsh School of Pharmacy , Cardiff University , Cardiff , UK.,b Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences , Cardiff University , Cardiff , UK
| | - Anna Scomparin
- c Department of Physiology and Pharmacology, Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
| | - Hanna Hailu
- a Centre for Polymer Therapeutics, Welsh School of Pharmacy , Cardiff University , Cardiff , UK
| | - Ronit Satchi-Fainaro
- c Department of Physiology and Pharmacology, Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel
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34
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Lucas AT, Herity LB, Kornblum ZA, Madden AJ, Gabizon A, Kabanov AV, Ajamie RT, Bender DM, Kulanthaivel P, Sanchez-Felix MV, Havel HA, Zamboni WC. Pharmacokinetic and screening studies of the interaction between mononuclear phagocyte system and nanoparticle formulations and colloid forming drugs. Int J Pharm 2017; 526:443-454. [DOI: 10.1016/j.ijpharm.2017.04.079] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 04/27/2017] [Accepted: 04/30/2017] [Indexed: 02/08/2023]
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Abstract
Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.
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Affiliation(s)
- Qi Wang
- School of Medicine, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Yi-Min Chao
- School of Chemistry, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK
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36
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Vahabi S, Eatemadi A. Nanoliposome encapsulated anesthetics for local anesthesia application. Biomed Pharmacother 2017; 86:1-7. [DOI: 10.1016/j.biopha.2016.11.137] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 11/28/2016] [Accepted: 11/28/2016] [Indexed: 12/14/2022] Open
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37
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Patnaik S. Nanomedicine Magic Bullet for Human Cancer. Oncology 2017. [DOI: 10.4018/978-1-5225-0549-5.ch014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Nanotechnology is the new tool that has changed healthcare, engineering, and space science. The technology involves nanoparticles that are effectively a bridge between bulk materials and atomic or molecular structures. The properties of materials change its surface plasmon resonance in metals, supermagnetism in magnetic materials as their size approaches to nanoscale. Taking in to account of their small sizes (less than 100nm) and their miraculous properties, unlike their precursor bulk material, nanoparticles are exploited to create new diagnostics and therapeutics with respect to several human diseases. Nanomedicine is generating a new generation of innovative revolution in nanoscale drug delivery strategies, site-specific drug delivery, and personalized therapy in cancer by releasing the drug at a specific site. This chapter discusses the evolution of nanomedicine to several advancements in the field of nanoparticle technologies, targeting and controlled release strategies, with the desire of generating robust and efficient nanotherapeutic tools against cancer.
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38
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Bayir E, Bilgi E, Urkmez AS. Implementation of Nanoparticles in Cancer Therapy. PHARMACEUTICAL SCIENCES 2017. [DOI: 10.4018/978-1-5225-1762-7.ch047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Cancer is a wide group of diseases and generally characterized by uncontrolled proliferation of cells whose metabolic activities are disrupted. Conventionally, chemotherapy, radiotherapy, and surgery are used in the treatment of cancer. However, in theory, even a single cancer cell may trigger recurrence. Therefore, these treatments cannot provide high survival rate for deadly types. Identification of alternative methods in treatment of cancers is inevitable because of adverse effects of conventional methods. In the last few decades, nanotechnology developed by scientists working in different disciplines—physics, chemistry, and biology—offers great opportunities. It is providing elimination of both circulating tumor cells and solid cancer cells by targeting cancer cells. In this chapter, inadequate parts of conventional treatment methods, nanoparticle types used in new treatment methods of cancer, and targeting methods of nanoparticles are summarized; furthermore, recommendations of future are provided.
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Lucas AT, White TF, Deal AM, Herity LB, Song G, Santos CM, Zamboni WC. Profiling the relationship between tumor-associated macrophages and pharmacokinetics of liposomal agents in preclinical murine models. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2016; 13:471-482. [PMID: 27720926 DOI: 10.1016/j.nano.2016.09.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 09/18/2016] [Accepted: 09/24/2016] [Indexed: 12/23/2022]
Abstract
The mononuclear phagocyte system (MPS) has previously been shown to significantly affect the clearance, tumor delivery, and efficacy of nanoparticles (NPs). This study profiled MPS cell infiltration in murine preclinical tumor models and evaluated how these differences may affect tumor disposition of PEGylated liposomal doxorubicin (PLD) in models sensitive and resistant to PLD. Significant differences in MPS presence existed between tumor types (e.g. ovarian versus endometrial), cell lines within the same tumor type, and location of tumor implantation (i.e. flank versus orthotopic xenografts). Further, the differences in MPS presence of SKOV-3 ovarian and HEC1A endometrial orthotopic cancer models may account for the 2.6-fold greater PLD tumor exposure in SKOV-3, despite similar plasma, liver and spleen exposures. These findings suggest that profiling the presence of MPS cells within and between tumor types is important in tumor model selection and in tumor types and patients likely to respond to NP treatment.
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Affiliation(s)
- Andrew T Lucas
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | | | - Allison M Deal
- Lineberger Comprehensive Cancer Center Biostatistics Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Leah B Herity
- UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA
| | - Gina Song
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Charlene M Santos
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; The Animal Studies Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - William C Zamboni
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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40
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Lencioni R, Cioni D. RFA plus lyso-thermosensitive liposomal doxorubicin: in search of the optimal approach to cure intermediate-size hepatocellular carcinoma. Hepat Oncol 2016; 3:193-200. [PMID: 30191041 DOI: 10.2217/hep-2016-0005] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 05/10/2016] [Indexed: 01/10/2023] Open
Abstract
When heated during a radiofrequency ablation (RFA) procedure to ≥40°C, lyso-thermosensitive liposomal doxorubicin (LTLD) produces high drug concentration in the surrounding margins of the ablation zone. The hypothesis that the RFA + LTLD combination can effectively treat hepatocellular carcinoma (HCC) was investigated in the HEAT study: adding LTLD did not improve the efficacy of normal practice RFA. However, among the 285 patients with a solitary lesion who received at least 45-min RFA dwell time, the hazard ratio for overall survival was 0.63 (95% CI: 0.41-0.96; p = 0.04). The OPTIMA study is currently ongoing to test the hypothesis that adding LTLD to a standardized RFA lasting ≥45 min increases survival compared with standardized RFA alone.
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Affiliation(s)
- Riccardo Lencioni
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Dania Cioni
- Department of Radiology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA
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41
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Song G, Suzuki OT, Santos CM, Lucas AT, Wiltshire T, Zamboni WC. Gulp1 is associated with the pharmacokinetics of PEGylated liposomal doxorubicin (PLD) in inbred mouse strains. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2016; 12:2007-2017. [PMID: 27288666 DOI: 10.1016/j.nano.2016.05.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 05/26/2016] [Accepted: 05/31/2016] [Indexed: 11/25/2022]
Abstract
Nanoparticles (NP) including liposomes are cleared by phagocytes of the mononuclear phagocyte system. High inter-patient variability in pharmacokinetics of PEGylated liposomal doxorubicin (PLD) has been reported. We hypothesized that genetic factors may be associated with the variable disposition of PLD. We evaluated plasma and tissue disposition of doxorubicin after administration of PLD at 6mg/kg IV ×1 via tail vein in 23 different male inbred mouse strains. An approximately 13-fold difference in plasma clearance of PLD was observed among inbred strains. We identified a correlation between strain-specific differences in PLD clearance and genetic variation within a genomic region encoding GULP1 (PTB domain containing engulfment adapter 1) protein using haplotype associated mapping and the efficient mixed-model association algorithms. Our results also show that Gulp1 expression in adipose tissue was associated with PLD disposition in plasma. Our findings suggest that genetic variants may be associated with inter-individual pharmacokinetic differences in NP clearance.
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Affiliation(s)
- Gina Song
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Oscar T Suzuki
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Charlene M Santos
- The Animal Studies Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Andrew T Lucas
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Tim Wiltshire
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - William C Zamboni
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Lucas AT, Madden AJ, Zamboni WC. Challenges in preclinical to clinical translation for anticancer carrier-mediated agents. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2016; 8:642-53. [PMID: 26846457 DOI: 10.1002/wnan.1394] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 12/14/2015] [Accepted: 01/05/2016] [Indexed: 02/03/2023]
Abstract
Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages over their small-molecule counterparts, there is substantial variability in how individual CMA formulations and patient characteristics affect the pharmacology, pharmacokinetics (PK), and pharmacodynamics (PD) (efficacy and toxicity) of these agents. Development or selection of animal models is used to predict the effects within a particular human disease. A breadth of studies have begun to emphasize the importance of preclinical animal models in understanding and evaluating the interaction between CMAs and the immune system and tumor matrix, which ultimately influences CMA PK (clearance and distribution) and PD (efficacy and toxicity). It is fundamental to study representative preclinical tumor models that recapitulate patients with diseases (e.g., cancer) and evaluate the interplay between CMAs and the immune system, including the mononuclear phagocyte system (MPS), chemokines, hormones, and other immune modulators. Furthermore, standard allometric scaling using body weight does not accurately predict drug clearance in humans. Future studies are warranted to better understand the complex pharmacology and interaction of CMA carriers within individual preclinical models and their biological systems, such as the MPS and tumor microenvironment, and their application to allometric scaling across species. WIREs Nanomed Nanobiotechnol 2016, 8:642-653. doi: 10.1002/wnan.1394 For further resources related to this article, please visit the WIREs website.
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Affiliation(s)
- Andrew T Lucas
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Andrew J Madden
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - William C Zamboni
- Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,UNC Institute for Pharmacogenomics and Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,UNC Lineberger Comprehensive Cancer Center, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Carolina Center of Cancer Nanotechnology Excellence, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Carolina Institute for NanoMedicine, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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The Importance of Particle Geometry in Design of Therapeutic and Imaging Nanovectors. ADVANCES IN DELIVERY SCIENCE AND TECHNOLOGY 2016. [DOI: 10.1007/978-1-4939-3634-2_8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Petschauer JS, Madden AJ, Kirschbrown WP, Song G, Zamboni WC. The effects of nanoparticle drug loading on the pharmacokinetics of anticancer agents. Nanomedicine (Lond) 2015; 10:447-63. [PMID: 25707978 DOI: 10.2217/nnm.14.179] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Major advances in carrier-mediated agents, which include nanoparticles, nanosomes and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages, such as greater solubility, duration of exposure and delivery to the site of action over their small-molecule counterparts, there is substantial variability in systemic clearance and distribution, tumor delivery and pharmacologic effects (efficacy and toxicity) of these agents. This review provides an overview of factors that affect the pharmacokinetics and pharmacodynamics of carrier-mediated agents in preclinical models and patients.
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Affiliation(s)
- Jennifer S Petschauer
- Division of Pharmacotherapy & Experimental Therapeutics, University of North Carolina at Chapel Hill (UNC) Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA
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Song G, Tarrant TK, White TF, Barrow DA, Santos CM, Timoshchenko RG, Hanna SK, Ramanathan RK, Lee CR, Bae-Jump VL, Gehrig PA, Zamboni WC. Roles of chemokines CCL2 and CCL5 in the pharmacokinetics of PEGylated liposomal doxorubicin in vivo and in patients with recurrent epithelial ovarian cancer. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 11:1797-807. [DOI: 10.1016/j.nano.2015.05.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 05/08/2015] [Accepted: 05/27/2015] [Indexed: 12/24/2022]
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Ajgal Z, Chapuis N, Emile G, Cessot A, Tigaud JM, Huillard O, Boudou-Rouquette P, Fontenay M, Goldwasser F, Alexandre J. Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia over time: assessment of monocyte count and baseline clinical parameters. Cancer Chemother Pharmacol 2015; 76:1033-9. [DOI: 10.1007/s00280-015-2875-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/15/2015] [Indexed: 02/07/2023]
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Lucas AT, Madden AJ, Zamboni WC. Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents. Expert Opin Drug Metab Toxicol 2015; 11:1419-33. [PMID: 26173794 DOI: 10.1517/17425255.2015.1057496] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages such as increased exposure duration, greater solubility and delivery to tumor sites over their small molecule counterparts, there is substantial variability in how individual CMA formulations affect the pharmacology, pharmacokinetics and pharmacodynamics (efficacy and toxicity) of these agents. AREAS COVERED CMA formulations are complex in nature compared to their small molecule counterparts and consist of multiple components and variables that can affect the pharmacological profile. This review provides an overview of factors that affect the pharmacologic profiles observed in CMA-formulated chemotherapy, primarily in liposomal formulations, that are currently in preclinical or early clinical development. EXPERT OPINION Despite the numerous advantages that CMA formulations provide, their clinical use is still in its infancy. It is critical that we understand the mechanisms and effects of CMAs in navigating biological barriers and how these factors affect their biodistribution and delivery to tumors. Future studies are warranted to better understand the complex pharmacology and interaction between CMA carriers and biological systems, such as the mononuclear phagocyte system and tumor microenvironment.
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Affiliation(s)
- Andrew T Lucas
- a 1 University of North Carolina at Chapel Hill (UNC), Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics , 120 Mason Farm Road, suite 1022B, CB 7361, Chapel Hill, NC 27599-7361, USA
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Wu H, Ramanathan RK, Zamboni BA, Strychor S, Ramalingam S, Edwards RP, Friedland DM, Stoller RG, Belani CP, Maruca LJ, Bang YJ, Zamboni WC. Population pharmacokinetics of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies. J Clin Pharmacol 2015; 52:180-94. [PMID: 21233302 DOI: 10.1177/0091270010394851] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
S-CKD602 is a pegylated long-circulating liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. A population pharmacokinetic (PK) model for encapsulated and released CKD-602 following administration of S-CKD602 was developed to assess factors that may influence S-CKD602 PK. Plasma samples from 45 patients with solid tumors were collected in a phase 1 study. S-CKD602 was administered as a 1-hour intravenous infusion with doses ranging from 0.1 to 2.5 mg/m(2) . Plasma concentrations of encapsulated and released CKD-602 were used to develop a population PK model using NONMEM. PK of encapsulated CKD-602 was described by a 1-compartment model with nonlinear clearance, and PK of released CKD-602 was described by a 2-compartment model with linear clearance for all patients. Covariate analysis revealed that tumor in the liver was a significant covariate for clearance of encapsulated CKD-602 and that age significantly influenced the release rate of CKD-602 from S-CKD602. Maximum elimination rate in patients with liver tumor is 1.5-fold higher compared with patients without liver tumor. Release rate of CKD-602 from S-CKD602 in patients less than 60 years old was 2.7-fold higher compared with patients 60 years old or older. These observations have potential implications in the optimal dosing of liposomal agents.
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Affiliation(s)
- Huali Wu
- University of North Carolina (UNC) Eshelman School of Pharmacy, UNC, Chapel Hill, North CarolinaUNC Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North CarolinaUNC Institute for Pharmacogenomics and Individualized Therapy, UNC, Chapel Hill, North CarolinaCarolina Center for Cancer Nanotechology Excellence, UNC, Chapel Hill, North CarolinaUniversity of Pittsburgh Cancer Institute, Pittsburgh, PennsylvaniaSchool of Medicine, University of Pittsburgh, PittsburghDepartment of Mathematics, Carlow University, PittsburghCKD Research Institute, Chonan, KoreaSeoul National University Hospital, Seoul, Korea
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Gobbo OL, Wetterling F, Vaes P, Teughels S, Markos F, Edge D, Shortt CM, Crosbie-Staunton K, Radomski MW, Volkov Y, Prina-Mello A. Biodistribution and pharmacokinetic studies of SPION using particle electron paramagnetic resonance, MRI and ICP-MS. Nanomedicine (Lond) 2015; 10:1751-60. [DOI: 10.2217/nnm.15.22] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: Superparamagnetic iron oxide nanoparticles (SPIONs) may play an important role in nanomedicine by serving as drug carriers and imaging agents. In this study, we present the biodistribution and pharmacokinetic properties of SPIONs using a new detection method, particle electron paramagnetic resonance (pEPR). Materials & methods: The pEPR technique is based on a low-field and low-frequency electron paramagnetic resonance. pEPR was compared with inductively coupled plasma mass spectrometry and MRI, in in vitro and in vivo. Results: The pEPR, inductively coupled plasma mass spectrometry and MRI results showed a good correlation between the techniques. Conclusion: The results indicate that pEPR can be used to detect SPIONs in both preclinical and clinical studies.
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Affiliation(s)
- Oliviero L Gobbo
- School of Pharmacy & Pharmaceutical Sciences, Dublin, Ireland
- Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
| | | | | | | | - Farouk Markos
- Department of Physiology, University College Cork, Cork, Ireland
| | - Deirdre Edge
- Department of Physiology, University College Cork, Cork, Ireland
| | | | | | | | - Yuri Volkov
- School of Medicine, Dublin, Ireland
- CRANN, Trinity College Dublin, Dublin, Ireland
| | - Adriele Prina-Mello
- School of Medicine, Dublin, Ireland
- CRANN, Trinity College Dublin, Dublin, Ireland
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Chen J, Yao Q, Wang H, Wang B, Zhang J, Wang T, Lv Y, Han Z, Wang L. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment. Med Oncol 2015; 32:184. [DOI: 10.1007/s12032-015-0634-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 05/08/2015] [Indexed: 11/29/2022]
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