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1
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Wang Y, Lin M, Fan T, Zhou M, Yin R, Wang X. Advances of Stimuli-Responsive Amphiphilic Copolymer Micelles in Tumor Therapy. Int J Nanomedicine 2025; 20:1-24. [PMID: 39776491 PMCID: PMC11700880 DOI: 10.2147/ijn.s495387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025] Open
Abstract
Amphiphilic copolymers are composed of both hydrophilic and hydrophobic chains, which can self-assemble into polymeric micelles in aqueous solution via the hydrophilic/hydrophobic interactions. Due to their unique properties, polymeric micelles have been widely used as drug carriers. Poorly soluble drugs can be covalently attached to polymer chains or non-covalently incorporated in the micelles, with improved pharmacokinetic profiles and enhanced efficacy. In recent years, stimuli-responsive amphiphilic copolymer micelles have attracted significant attention. These micelles can respond to specific stimuli, including physical triggers (light, temperature, etc). chemical stimuli (pH, redox, etc). and physiological factors (enzymes, ATP, etc). Under these stimuli, the structures or properties of the micelles can change, enabling targeted therapy and controlled drug release in tumors. These stimuli-responsive strategies offer new avenues and approaches to enhance the tumor efficacy and reduce drug side effects. We will review the applications of different types of stimuli-responsive amphiphilic copolymer micelles in tumor therapy, aiming to provide valuable guidance for future research directions and clinical translation.
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Affiliation(s)
- Yao Wang
- Department of pharmacy, west china hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Meng Lin
- Department of pharmacy, west china hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Tianfei Fan
- Department of pharmacy, west china hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Minglu Zhou
- Department of pharmacy, west china hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Ruxi Yin
- Department of pharmacy, west china hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Xueyan Wang
- Department of pharmacy, west china hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
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2
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Park SA, Hwang D, Kim JH, Lee SY, Lee J, Kim HS, Kim KA, Lim B, Lee JE, Jeon YH, Oh TJ, Lee J, An S. Formulation of lipid nanoparticles containing ginsenoside Rg2 and protopanaxadiol for highly efficient delivery of mRNA. Biomater Sci 2024. [PMID: 39480551 DOI: 10.1039/d4bm01070a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Abstract
Lipid nanoparticles (LNPs) are widely recognized as crucial carriers of mRNA in therapeutic and vaccine development. The typical lipid composition of mRNA-LNP systems includes an ionizable lipid, a helper lipid, a polyethylene glycol (PEG)-lipid, and cholesterol. Concerns arise regarding cholesterol's susceptibility to oxidation, potentially leading to undesired immunological responses and toxicity. In this study, we formulated novel LNPs by replacing cholesterol with phytochemical-derived compounds, specifically ginsenoside Rg2 and its derivative phytosterol protopanaxadiol (PPD), and validated their efficacy as mRNA delivery systems. The mRNA-LNP complexes were manually prepared through a simple mixing process. The biocompatibility of these Rg2-based LNPs (Rg2-LNP) and PPD-based LNPs (PPD-LNP) was assessed through cell viability assays, while the protective function of LNPs for mRNA was demonstrated by RNase treatment. Enhanced green fluorescent protein (EGFP) mRNA delivery and expression in A549 and HeLa cells were analyzed using optical microscopy and flow cytometry. The expression efficiency of Rg2-LNP and PPD-LNP was compared with that of commercially available LNPs, with both novel formulations demonstrating superior transfection and EGFP expression. Furthermore, in vivo tests following intramuscular (I.M.) injection in hairless mice demonstrated efficient luciferase (Luc) mRNA delivery and effective Luc expression using Rg2-LNP and PPD-LNP compared to commercial LNPs. Results indicated that the efficiency of EGFP and Luc expression in Rg2-LNP and PPD-LNP surpassed that of the cholesterol-based LNP formulation. These findings suggest that Rg2-LNP and PPD-LNP are promising candidates for future drug and gene delivery systems.
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Affiliation(s)
- Sin A Park
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
| | - Dajeong Hwang
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
| | - Jae Hoon Kim
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
| | - Seung-Yeul Lee
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
| | - Jaebeom Lee
- Department of Chemistry, Chungnam National University, Yuseong-gu, Daejeon, 34134, Republic of Korea
- Department of Chemical Engineering and Applied Chemistry, Chungnam National University, Yuseong-gu, Daejeon, 34134, Republic of Korea
| | - Han Sang Kim
- Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyung-A Kim
- Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Bumhee Lim
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), Dong-gu, Daegu, 41061, Republic of Korea
| | - Jae-Eon Lee
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), Dong-gu, Daegu, 41061, Republic of Korea
| | - Yong Hyun Jeon
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDIhub), Dong-gu, Daegu, 41061, Republic of Korea
| | - Tae Jeong Oh
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
| | - Jaewook Lee
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
| | - Sungwhan An
- Genomictree Inc., Yuseong-gu, Daejeon, 34027, Republic of Korea.
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3
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Hirschbiegel CM, Zhang X, Huang R, Cicek YA, Fedeli S, Rotello VM. Inorganic nanoparticles as scaffolds for bioorthogonal catalysts. Adv Drug Deliv Rev 2023; 195:114730. [PMID: 36791809 PMCID: PMC10170407 DOI: 10.1016/j.addr.2023.114730] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/15/2023]
Abstract
Bioorthogonal transition metal catalysts (TMCs) transform therapeutically inactive molecules (pro-drugs) into active drug compounds. Inorganic nanoscaffolds protect and solubilize catalysts while offering a flexible design space for decoration with targeting elements and stimuli-responsive activity. These "drug factories" can activate pro-drugs in situ, localizing treatment to the disease site and minimizing off-target effects. Inorganic nanoscaffolds provide structurally diverse scaffolds for encapsulating TMCs. This ability to define the catalyst environment can be employed to enhance the stability and selectivity of the TMC, providing access to enzyme-like bioorthogonal processes. The use of inorganic nanomaterials as scaffolds TMCs and the use of these bioorthogonal nanozymes in vitro and in vivo applications will be discussed in this review.
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Affiliation(s)
| | - Xianzhi Zhang
- Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St, Amherst, MA 01003, USA
| | - Rui Huang
- Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St, Amherst, MA 01003, USA
| | - Yagiz Anil Cicek
- Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St, Amherst, MA 01003, USA
| | - Stefano Fedeli
- Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St, Amherst, MA 01003, USA
| | - Vincent M Rotello
- Department of Chemistry, University of Massachusetts Amherst, 710 N. Pleasant St, Amherst, MA 01003, USA.
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4
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Singh S, Sharma N, Shukla S, Behl T, Gupta S, Anwer MK, Vargas-De-La-Cruz C, Bungau SG, Brisc C. Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics. Molecules 2023; 28:molecules28062811. [PMID: 36985782 PMCID: PMC10057127 DOI: 10.3390/molecules28062811] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/15/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.
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Affiliation(s)
- Sukhbir Singh
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala 133207, Haryana, India
| | - Neelam Sharma
- Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala 133207, Haryana, India
| | - Saurabh Shukla
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Tapan Behl
- School of Health Sciences &Technology, University of Petroleum and Energy Studies, Dehradun 248007, Uttarakhand, India
| | - Sumeet Gupta
- Department of Pharmacology, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala 133207, Haryana, India
| | - Md Khalid Anwer
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Celia Vargas-De-La-Cruz
- Department of Pharmacology, Bromatology and Toxicology, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima 150001, Peru
- E-Health Research Center, Universidad de Ciencias y Humanidades, Lima 15001, Peru
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Doctoral School of Biomedical Sciences, University of Oradea, 410087 Oradea, Romania
| | - Cristina Brisc
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
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5
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Hashemi M, Ghadyani F, Hasani S, Olyaee Y, Raei B, Khodadadi M, Ziyarani MF, Basti FA, Tavakolpournegari A, Matinahmadi A, Salimimoghadam S, Aref AR, Taheriazam A, Entezari M, Ertas YN. Nanoliposomes for doxorubicin delivery: Reversing drug resistance, stimuli-responsive carriers and clinical translation. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.104112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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6
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Boafo GF, Magar KT, Ekpo MD, Qian W, Tan S, Chen C. The Role of Cryoprotective Agents in Liposome Stabilization and Preservation. Int J Mol Sci 2022; 23:ijms232012487. [PMID: 36293340 PMCID: PMC9603853 DOI: 10.3390/ijms232012487] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/22/2022] [Accepted: 10/15/2022] [Indexed: 11/18/2022] Open
Abstract
To improve liposomes’ usage as drug delivery vehicles, cryoprotectants can be utilized to prevent constituent leakage and liposome instability. Cryoprotective agents (CPAs) or cryoprotectants can protect liposomes from the mechanical stress of ice by vitrifying at a specific temperature, which forms a glassy matrix. The majority of studies on cryoprotectants demonstrate that as the concentration of the cryoprotectant is increased, the liposomal stability improves, resulting in decreased aggregation. The effectiveness of CPAs in maintaining liposome stability in the aqueous state essentially depends on a complex interaction between protectants and bilayer composition. Furthermore, different types of CPAs have distinct effective mechanisms of action; therefore, the combination of several cryoprotectants may be beneficial and novel attributed to the synergistic actions of the CPAs. In this review, we discuss the use of liposomes as drug delivery vehicles, phospholipid–CPA interactions, their thermotropic behavior during freezing, types of CPA and their mechanism for preventing leakage of drugs from liposomes.
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Affiliation(s)
- George Frimpong Boafo
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
| | - Kosheli Thapa Magar
- Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Marlene Davis Ekpo
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
| | - Wang Qian
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
| | - Songwen Tan
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
- Correspondence: (S.T.); (C.C.)
| | - Chuanpin Chen
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
- Correspondence: (S.T.); (C.C.)
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7
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Torrik A, Zaerin S, Zarif M. Doxorubicin and Imatinib co-drug delivery using non-covalently functionalized carbon nanotube: Molecular dynamics study. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.119789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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8
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Dash BS, Lu YJ, Pejrprim P, Lan YH, Chen JP. Hyaluronic acid-modified, IR780-conjugated and doxorubicin-loaded reduced graphene oxide for targeted cancer chemo/photothermal/photodynamic therapy. BIOMATERIALS ADVANCES 2022; 136:212764. [PMID: 35929292 DOI: 10.1016/j.bioadv.2022.212764] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 03/04/2022] [Accepted: 03/13/2022] [Indexed: 10/18/2022]
Abstract
We used reduced graphene oxide (rGO), which has two times higher photothermal conversion efficiency than graphene oxide (GO), as a photothermal agent for cancer photothermal therapy (PTT). By conjugating a photosensitizer IR780 to rGO, the IR780-rGO could be endowed with reactive oxygen species (ROSs) generation ability for concurrent photodynamic therapy (PDT). The IR780-rGO was coated with hyaluronic acid (HA) by electrostatic interaction to facilitate its intracellular uptake by U87 glioblastoma cells. The IR780-rGO/HA was loaded with doxorubicin (DOX) for chemotherapy (CT), to develop a pH-responsive drug delivery nano-platform for targeted multimodal cancer CT/PTT/PDT. We fully characterized the properties of all nanocomposites during the synthesis steps. The high loading efficiency of DOX on IR780-rGO-HA provides 3 mg/mg drug loading, while IR780-rGO-HA/DOX shows 3 times higher drug release at endosomal pH value (pH 5) than at pH 7.4. The mechanism for PTT/PDT was confirmed from the ability of IR780-rGO-HA to induce time-dependent temperature rise, synthesis of heat shock protein 70 (HSP70) and generation of intracellular ROSs, after exposure to 808 nm near infrared (NIR) laser light. The nano-vehicle IR780-rGO-HA shows high biocompatibility toward 3T3 fibroblast and U87 cancer cell lines, as well as enhanced intracellular uptake by U87 through active targeting. This translates into increased cytotoxicity of IR780-rGO-HA/DOX, by lowering the drug half-maximal inhibitory concentration (IC50) from 0.7 to 0.46 μg/mL. This IC50 is further decreased to 0.1 μg/mL by irradiation with NIR laser for 3 min at 1.5 W/cm2. The elevated cancer cell killing mechanism was supported from flow cytometry analysis, where the highest cell apoptosis/necrosis rate was observed in combination CT/PTT/PDT. Using xenograft tumor model created by subcutaneous implantation of U87 cells in nude mice, IR780-rGO-HA/DOX delivered through intravenous (IV) injection and followed with 808 nm laser treatment for 5 min at 1.5 W/cm2 results in the lowest tumor growth rate, with negligible change of tumor volume from its original value at the end 20-day observation period. The therapeutic efficacy was supported from inhibited cell proliferation rate, increased cell apoptosis rate, and increased production of HSP70 from immunohistochemical staining of tumor tissue slices. The safety of the NIR-assisted multimodal cancer treatment could be confirmed from non-significant change of body weight and hematological parameters of blood sample. Taken together, we conclude that IV delivery of IR780-rGO-HA/DOX plus NIR laser treatment is an effective nanomedicine approach for combination cancer therapy.
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Affiliation(s)
- Banendu Sunder Dash
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
| | - Yu-Jen Lu
- Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan; School of Medicine, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
| | - Pidsarintun Pejrprim
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
| | - Yu-Hsiang Lan
- School of Medicine, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
| | - Jyh-Ping Chen
- Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan; Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan; Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan; Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan.
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9
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Zhou L, Li Y, Liang Q, Liu J, Liu Y. Combination therapy based on targeted nano drug co-delivery systems for liver fibrosis treatment: A review. J Drug Target 2022; 30:577-588. [PMID: 35179094 DOI: 10.1080/1061186x.2022.2044485] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Liver fibrosis is the hallmark of liver disease and occurs prior to the stages of cirrhosis and hepatocellular carcinoma. Any type of liver damage or inflammation can result in fibrosis. Fibrosis does not develop overnight, but rather as a result of the long-term action of injury factors. At present, however, there are no good treatment methods or specific drugs other than removing the pathogenic factors. Drug application is still limited, which means that drugs with good performance in vitro cannot achieve good therapeutic effects in vivo, owing to various factors such as poor drug targeting, large side effects, and strong hydrophobicity. Hepatic stellate cells (HSC) are the primary effector cells in liver fibrosis. The nano-drug delivery system is a new and safe drug delivery system that has many advantages which are widely used in the field of liver fibrosis. Drug resistance and side effects can be reduced when two or more drugs are used in combination drug delivery. Combination therapy of drugs with different targets has emerged as a novel approach to treating liver fibrosis, and the nano co-delivery system enhances the benefits of combination therapy. While nano co-delivery systems can maximize benefits while avoiding drug side effects, this is precisely the advantage of the nano co-delivery system. This review briefly described the pathogenesis and current treatment strategies, the different co-delivery systems of combination drugs in the nano delivery system, and targeting strategies for nano delivery systems on liver fibrosis therapy. Because of their superior performance, nano delivery systems and targeting drug delivery systems have received a lot of attention in the new drug delivery system. The new delivery systems offer a new pathway in the treatment of liver fibrosis, and it is believed that it can be a new treatment for fibrosis in the future. Nano co-delivery system of combination drugs and targeting strategies has proven the effectiveness of anti-fibrosis at the experimental level.
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Affiliation(s)
- Liyue Zhou
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Yifan Li
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Qiangwei Liang
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Jinxia Liu
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Yanhua Liu
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China.,Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China
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Utilizing Sphingomyelinase Sensitizing Liposomes in Imaging Intestinal Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis. Biomedicines 2022; 10:biomedicines10020413. [PMID: 35203622 PMCID: PMC8962329 DOI: 10.3390/biomedicines10020413] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 02/05/2022] [Accepted: 02/06/2022] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, resulting in severe symptoms. At the moment, the goal of medical treatments is to reduce inflammation. IBD is treated with systemic anti-inflammatory compounds, but they have serious side effects. The treatment that is most efficient and causes the fewest side effects would be the delivery of the drugs on the disease site. This study aimed to investigate the suitability of sphingomyelin (SM) containing liposomes to specifically target areas of inflammation in dextran sulfate sodium-induced murine colitis. Sphingomyelin is a substrate to the sphingomyelinase enzyme, which is only present outside cells in cell stress, like inflammation. When sphingomyelin consisting of liposomes is predisposed to the enzyme, it causes the weakening of the membrane structure. We demonstrated that SM-liposomes are efficiently taken up in intestinal macrophages, indicating their delivery potential. Furthermore, our studies showed that sphingomyelinase activity and release are increased in a dextran sulfate sodium-induced IBD mouse model. The enzyme appearance in IBD disease was also traced in intestine samples of the dextran sulfate sodium-treated mice and human tissue samples. The results from the IBD diseased animals, treated with fluorescently labeled SM-liposomes, demonstrated that the liposomes were taken up preferentially in the inflamed colon. This uptake efficiency correlated with sphingomyelinase activity.
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11
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Aslam H, Shukrullah S, Naz MY, Fatima H, Hussain H, Ullah S, Assiri MA. Current and future perspectives of multifunctional magnetic nanoparticles based controlled drug delivery systems. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2021.102946] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
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12
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Helmholz H, Will O, Penate-Medina T, Humbert J, Damm T, Luthringer-Feyerabend B, Willumeit-Römer R, Glüer CC, Penate-Medina O. Tissue responses after implantation of biodegradable Mg alloys evaluated by multimodality 3D micro-bioimaging in vivo. J Biomed Mater Res A 2021; 109:1521-1529. [PMID: 33590952 DOI: 10.1002/jbm.a.37148] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 12/07/2020] [Accepted: 01/25/2021] [Indexed: 12/12/2022]
Abstract
The local response of tissue triggered by implantation of degradable magnesium-based implant materials was investigated in vivo in a murine model. Pins (5.0 mm length by 0.5 mm diameter) made of Mg, Mg-10Gd, and Ti were implanted in the leg muscle tissue of C57Bl/6N mice (n = 6). Implantation was generally well tolerated as documented by only a mild short term increase in a multidimensional scoring index. Lack of difference between the groups indicated that the response was systemic and surgery related rather than material dependent. Longitudinal in vivo monitoring utilizing micro-computed tomography over 42 days demonstrated the highest and most heterogeneous degradation for Mg-10Gd. Elemental imaging of the explants by micro X-ray fluorescence spectrometry showed a dense calcium-phosphate-containing degradation layer. In order to monitor resulting surgery induced and/or implant material associated local cell stress, sphingomyelin based liposomes containing indocyanine green were administered. An initial increase in fluorescent signals (3-7 days after implantation) indicating cell stress at the site of the implantation was measured by in vivo fluorescent molecular tomography. The signal decreased until the 42nd day for all materials. These findings demonstrate that Mg based implants are well tolerated causing only mild and short term adverse reactions.
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Affiliation(s)
- Heike Helmholz
- Department Biological Characterization, Helmholtz-Center Geesthacht Institute for Material and Coastal Research; Institute of Materials Research, Division of Metallic Biomaterials, Geesthacht, Germany
| | - Olga Will
- Section Biomedical Imaging and Molecular Imaging, North Competence Center, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Tuula Penate-Medina
- Section Biomedical Imaging and Molecular Imaging, North Competence Center, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Jana Humbert
- Section Biomedical Imaging and Molecular Imaging, North Competence Center, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Timo Damm
- Section Biomedical Imaging and Molecular Imaging, North Competence Center, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Berengere Luthringer-Feyerabend
- Department Biological Characterization, Helmholtz-Center Geesthacht Institute for Material and Coastal Research; Institute of Materials Research, Division of Metallic Biomaterials, Geesthacht, Germany
| | - Regine Willumeit-Römer
- Department Biological Characterization, Helmholtz-Center Geesthacht Institute for Material and Coastal Research; Institute of Materials Research, Division of Metallic Biomaterials, Geesthacht, Germany
| | - Claus-Christian Glüer
- Section Biomedical Imaging and Molecular Imaging, North Competence Center, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
| | - Oula Penate-Medina
- Section Biomedical Imaging and Molecular Imaging, North Competence Center, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
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13
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Lima PHCD, Butera AP, Cabeça LF, Ribeiro-Viana RM. Liposome surface modification by phospholipid chemical reactions. Chem Phys Lipids 2021; 237:105084. [PMID: 33891960 DOI: 10.1016/j.chemphyslip.2021.105084] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/17/2021] [Accepted: 04/16/2021] [Indexed: 12/13/2022]
Abstract
Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug delivery, diagnosis, and in many other academic areas. A novel class of this nanoparticle is the actively target liposome, which is constructed with the surface modified with appropriated molecules (or ligands) to actively bind a target molecule of certain cells, system, or tissue. There are many ways to functionalize these nanostructures, from non-covalent adsorption to covalent bond formation. In this review, we focus on the strategies of modifying liposomes by glycerophospholipid covalent chemical reaction. The approach used in this text summarizes the main reactions and strategies used in phospholipid modification that can be carried out by chemists and researchers from other areas. The knowledge of these methodologies is of great importance for planning new studies using this material and also for manipulating its properties.
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Affiliation(s)
- Pedro Henrique Correia de Lima
- Programa de Pós-graduação em Ciências e Engenharia de Materiais (PPGCEM-UTFPR), Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil
| | - Anna Paola Butera
- Departamento de Química, Universidade Estadual de Londrina, UEL, CEP 86051-980, Londrina, PR, Brazil
| | - Luis Fernando Cabeça
- Programa de Pós-graduação em Ciências e Engenharia de Materiais (PPGCEM-UTFPR), Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil; Departamento Acadêmico de Química, Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil
| | - Renato Márcio Ribeiro-Viana
- Programa de Pós-graduação em Ciências e Engenharia de Materiais (PPGCEM-UTFPR), Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil; Departamento Acadêmico de Química, Universidade Tecnológica Federal do Paraná, UTFPR-Ld, CEP 86036-370, Londrina, PR, Brazil.
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Acid-Sphingomyelinase Triggered Fluorescently Labeled Sphingomyelin Containing Liposomes in Tumor Diagnosis after Radiation-Induced Stress. Int J Mol Sci 2021; 22:ijms22083864. [PMID: 33917976 PMCID: PMC8068344 DOI: 10.3390/ijms22083864] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/26/2021] [Accepted: 03/29/2021] [Indexed: 11/21/2022] Open
Abstract
In liposomal delivery, a big question is how to release the loaded material into the correct place. Here, we will test the targeting and release abilities of our sphingomyelin-consisting liposome. A change in release parameters can be observed when sphingomyelin-containing liposome is treated with sphingomyelinase enzyme. Sphingomyelinase is known to be endogenously released from the different cells in stress situations. We assume the effective enzyme treatment will weaken the liposome making it also leakier. To test the release abilities of the SM-liposome, we developed several fluorescence-based experiments. In in vitro studies, we used molecular quenching to study the sphingomyelinase enzyme-based release from the liposomes. We could show that the enzyme treatment releases loaded fluorescent markers from sphingomyelin-containing liposomes. Moreover, the release correlated with used enzymatic activities. We studied whether the stress-related enzyme expression is increased if the cells are treated with radiation as a stress inducer. It appeared that the radiation caused increased enzymatic activity. We studied our liposomes’ biodistribution in the animal tumor model when the tumor was under radiation stress. Increased targeting of the fluorescent marker loaded to our liposomes could be found on the site of cancer. The liposomal targeting in vivo could be improved by radiation. Based on our studies, we propose sphingomyelin-containing liposomes can be used as a controlled release system sensitive to cell stress.
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15
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Chmykhalo V, Belanova A, Belousova M, Butova V, Makarenko Y, Khrenkova V, Soldatov A, Zolotukhin P. Microbial-based magnetic nanoparticles production: a mini-review. Integr Biol (Camb) 2021; 13:98-107. [PMID: 33829272 DOI: 10.1093/intbio/zyab005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 02/16/2021] [Accepted: 02/18/2021] [Indexed: 11/14/2022]
Abstract
The ever-increasing biomedical application of magnetic nanoparticles (MNPs) implies increasing demand in their scalable and high-throughput production, with finely tuned and well-controlled characteristics. One of the options to meet the demand is microbial production by nanoparticles-synthesizing bacteria. This approach has several benefits over the standard chemical synthesis methods, including improved homogeneity of synthesis, cost-effectiveness, safety and eco-friendliness. There are, however, specific challenges emanating from the nature of the approach that are to be accounted and resolved in each manufacturing instance. Most of the challenges can be resolved by proper selection of the producing organism and optimizing cell culture and nanoparticles extraction conditions. Other issues require development of proper continuous production equipment, medium usage optimization and precursor ions recycling. This mini-review focuses on the related topics in microbial synthesis of MNPs: producing organisms, culturing methods, nanoparticles characteristics tuning, nanoparticles yield and synthesis timeframe considerations, nanoparticles isolation as well as on the respective challenges and possible solutions.
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Affiliation(s)
- Victor Chmykhalo
- Academy of Biology and Biotechnology, Southern Federal University, Rostov-on-Don, Russia
| | - Anna Belanova
- Smart Materials International Research Centre, Southern Federal University, Rostov-on-Don, Russia
| | - Mariya Belousova
- English Language Department for Natural Sciences Faculties, Southern Federal University, Rostov-on-Don, Russia
| | - Vera Butova
- Smart Materials International Research Centre, Southern Federal University, Rostov-on-Don, Russia
| | | | - Vera Khrenkova
- Medical Consulting Department, Rostov-on-Don Pathological-Anatomical Bureau No. 1, Rostov-on-Don, Russia
| | - Alexander Soldatov
- Smart Materials International Research Centre, Southern Federal University, Rostov-on-Don, Russia
| | - Peter Zolotukhin
- Academy of Biology and Biotechnology, Southern Federal University, Rostov-on-Don, Russia
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Peñate-Medina T, Kraas E, Luo K, Humbert J, Zhu H, Mertens F, Gerle M, Rohwedder A, Damoah C, Will O, Acil Y, Kairemo K, Wiltfang J, Glüer CC, Scherließ R, Sebens S, Peñate-Medina OP. Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification <i>In vitro</i> and <i>In vivo</i> in Imaging Setups. Curr Pharm Des 2021; 26:3828-3833. [PMID: 32188378 DOI: 10.2174/1381612826666200318170849] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 12/13/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. METHODS Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. RESULTS We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. CONCLUSION Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.
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Affiliation(s)
- Tuula Peñate-Medina
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Eike Kraas
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Kunliang Luo
- Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitatsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universitat zu Kiel, Germany
| | - Jana Humbert
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Hanwen Zhu
- Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitatsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universitat zu Kiel, Germany
| | - Fabian Mertens
- Christian-Albrechts-Universität Kiel, Department of Pharmaceutics and Biopharmaceutics, Grasweg 9a D-24118 Kiel, Germany
| | - Mirko Gerle
- Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitatsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universitat zu Kiel, Germany
| | - Arndt Rohwedder
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Christabel Damoah
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Olga Will
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Yahya Acil
- Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitatsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universitat zu Kiel, Germany
| | - Kalevi Kairemo
- Department of Nuclear Medicine - The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jörg Wiltfang
- Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitatsklinikum Schleswig-Holstein Campus Kiel, Christian Albrechts Universitat zu Kiel, Germany
| | - Claus-C Glüer
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Regina Scherließ
- Christian-Albrechts-Universitat Kiel, Department of Pharmaceutics and Biopharmaceutics, Grasweg 9a D-24118 Kiel, Germany
| | - Susanne Sebens
- Institut für Experimentelle Tumorforschung (IET), Arnold-Heller-Str. 3, Building U3024105, Kiel, Germany
| | - Oula Peñate Peñate-Medina
- Institut für Experimentelle Tumorforschung (IET), Arnold-Heller-Str. 3, Building U3024105, Kiel, Germany
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Peñate-Medina T, Damoah C, Benezra M, Will O, Kairemo K, Humbert J, Sebens S, Peñate-Medina O. Alpha-MSH Targeted Liposomal Nanoparticle for Imaging in Inflammatory Bowel Disease (IBD). Curr Pharm Des 2020; 26:3840-3846. [DOI: 10.2174/1381612826666200727002716] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 04/27/2020] [Indexed: 02/08/2023]
Abstract
Background:
The purpose of our study was to find a novel targeted imaging and drug delivery vehicle
for inflammatory bowel disease (IBD). IBD is a common and troublesome disease that still lacks effective therapy
and imaging options. As an attempt to improve the disease treatment, we tested αMSH for the targeting of
nanoliposomes to IBD sites. αMSH, an endogenous tridecapeptide, binds to the melanocortin-1 receptor (MC1-R)
and has anti-inflammatory and immunomodulating effects. MC1-R is found on macrophages, neutrophils and the
renal tubule system. We formulated and tested a liposomal nanoparticle involving αMSH in order to achieve a
specific targeting to the inflamed intestines.
Methods:
NDP-αMSH peptide conjugated to Alexa Fluor™ 680 was linked to the liposomal membrane via NSuccinyl
PE and additionally loaded into the lumen of the liposomes. Liposomes without the αMSH-conjugate
and free NDP-αMSH were used as a control. The liposomes were also loaded with ICG to track them. The
liposomes were tested in DSS treated mice, which had received DSS via drinking water order to develop a model
IBD. Inflammation severity was assessed by the Disease Activity Index (DAI) score and ex vivo histological
CD68 staining of samples taken from different parts of the intestine. The liposome targeting was analyzed by
analyzing the ICG and ALEXA 680 fluorescence in the intestine compared to the biodistribution.
Results:
NPD-αMSH was successfully labeled with Alexa and retained its biological activity. Liposomes were
identified in expected regions in the inflamed bowel regions and in the kidneys, where MC1-R is abundant. In
vivo liposome targeting correlated with the macrophage concentration at the site of the inflammation supporting
the active targeting of the liposomes through αMSH. The liposomal αMSH was well tolerated by animals.
Conclusions:
This study opens up the possibility to further develop an αMSH targeted theranostic delivery to
different clinically relevant applications in IBD inflammation but also opens possibilities for use in other inflammations
like lung inflammation in Covid 19.
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Affiliation(s)
- Tuula Peñate-Medina
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Christabel Damoah
- Institut fur Experimentelle Tumorforschung (IET), Arnold-Heller-Str. 3, Building U30 24105 Kiel, Germany
| | - Miriam Benezra
- Department of Biology, Touro College, New-York, NY 10006, and Department of Natural Science, Baruch College, New- York, NY 10010, United States
| | - Olga Will
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Kalevi Kairemo
- Department of Nuclear Medicine - The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jana Humbert
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
| | - Susanne Sebens
- Institut fur Experimentelle Tumorforschung (IET), Arnold-Heller-Str. 3, Building U30 24105 Kiel, Germany
| | - Oula Peñate-Medina
- Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein (UKSH), Kiel University, Kiel, Germany
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Radwan SAA, El-Maadawy WH, ElMeshad AN, Shoukri RA, Yousry C. Impact of Reverse Micelle Loaded Lipid Nanocapsules on the Delivery of Gallic Acid into Activated Hepatic Stellate Cells: A Promising Therapeutic Approach for Hepatic Fibrosis. Pharm Res 2020; 37:180. [PMID: 32875435 DOI: 10.1007/s11095-020-02891-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE Gallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression. METHODS GA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored. RESULTS Nano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats' livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities, effective internalization into aHSCs, marked down-regulation in pro-fibrogenic biomarkers' expressions and elevated HSCs' apoptosis. CONCLUSIONS These findings emphasize the promising application of RMLNC as a delivery system in hepatic fibrosis treatment, where successful delivery of GA into aHSCs was ensured via increased cellular uptake and antifibrotic activities.
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Affiliation(s)
- Shaimaa Ali Ali Radwan
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al Aini street, PO Box 11562, Cairo, Egypt.
| | - Walaa H El-Maadawy
- Department of Pharmacology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt
| | - Aliaa Nabil ElMeshad
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al Aini street, PO Box 11562, Cairo, Egypt
| | - Raguia Aly Shoukri
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al Aini street, PO Box 11562, Cairo, Egypt
| | - Carol Yousry
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr Al Aini street, PO Box 11562, Cairo, Egypt
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Zhang N, Tan Y, Yan L, Zhang C, Xu M, Guo H, Zhuang B, Zhou L, Xie X. Modulation of Tumor Hypoxia by pH-Responsive Liposomes to Inhibit Mitochondrial Respiration for Enhancing Sonodynamic Therapy. Int J Nanomedicine 2020; 15:5687-5700. [PMID: 32821097 PMCID: PMC7418152 DOI: 10.2147/ijn.s256038] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 07/17/2020] [Indexed: 01/04/2023] Open
Abstract
Background and Purpose Sonodynamic therapy (SDT) has been widely used for the noninvasive treatment of solid tumors, but the hypoxic tumor microenvironment limits its therapeutic effect. The current methods of reoxygenation to enhance SDT have limitations, prompting reconsideration of the design of therapeutic approaches. Here, we developed a tumor microenvironment-responsive nanoplatform by reducing oxygen consumption to overcome hypoxia-induced resistance to cancer therapy. Methods A pH-responsive drug-loaded liposome (MI-PEOz-lip) was prepared and used to reduce oxygen consumption, attenuating hypoxia-induced resistance to SDT and thereby improving therapeutic efficiency. Photoacoustic imaging (PAI) and fluorescence imaging (FI) of MI-PEOz-lip were evaluated in vitro and in breast xenograft tumor models. The pH-sensitive functionality of MI-PEOz-lip was applied for pH-triggered cargo release, and its capacity was evaluated. The MI-PEOz-lip-mediated SDT effect was compared with other treatments in vivo. Results MI-PEOz-lip was demonstrated to specifically accumulate in tumors. Metformin molecules in liposomes selectively accumulate in tumors by pH-responsive drug release to inhibit the mitochondrial respiratory chain while releasing IR780 to the tumor area. These pH-responsive liposomes demonstrated PAI and FI imaging capabilities in vitro and in vivo, providing potential for treatment guidance and monitoring. In particular, the prepared MI-PEOz-lip combined with ultrasound irradiation effectively inhibited breast tumors by producing toxic reactive singlet oxygen species (ROS), while the introduction of metformin inhibited mitochondrial respiration and reduced tumor oxygen consumption, resulting in excellent sonodynamic therapy performance compared with other treatments. Conclusion In this study, we present a novel strategy to achieve high therapeutic efficacy of SDT by the rational design of multifunctional nanoplatforms. This work provides a new strategy that can solve the current problems of inefficient oxygen delivery strategies and weaken resistance to various oxygen-dependent therapies.
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Affiliation(s)
- Nan Zhang
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Yang Tan
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Liwei Yan
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Chunyang Zhang
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Ming Xu
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Huanling Guo
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Bowen Zhuang
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Luyao Zhou
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China
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Galdioli Pellá MC, Simão AR, Lima-Tenório MK, Tenório-Neto E, Scariot DB, Nakamura CV, Rubira AF. Chitosan hybrid microgels for oral drug delivery. Carbohydr Polym 2020; 239:116236. [DOI: 10.1016/j.carbpol.2020.116236] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 03/25/2020] [Accepted: 03/27/2020] [Indexed: 01/13/2023]
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Zhao S, Li J, Wang F, Yu T, Zhou Y, He L, Zhang Y, Yang J. Semi-elastic core-shell nanoparticles enhanced the oral bioavailability of peptide drugs. CHINESE CHEM LETT 2020. [DOI: 10.1016/j.cclet.2019.07.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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22
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Tang B, Peng Y, Yue Q, Pu Y, Li R, Zhao Y, Hai L, Guo L, Wu Y. Design, preparation and evaluation of different branched biotin modified liposomes for targeting breast cancer. Eur J Med Chem 2020; 193:112204. [PMID: 32172035 DOI: 10.1016/j.ejmech.2020.112204] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 03/02/2020] [Accepted: 03/02/2020] [Indexed: 12/19/2022]
Abstract
A series of liposome ligands (Bio-Chol, Bio-Bio-Chol, tri-Bio-Chol and tetra-Bio-Chol) modified by different branched biotins that can recognize the SMVT receptors over-expressed in breast cancer cells were synthesized. And four liposomes (Bio-Lip, Bio-Bio-Lip, tri-Bio-Lip and tetra-Bio-Lip) modified by above mentioned ligands as well as the unmodified liposome (Lip) were prepared to study the targeting ability for breast cancer. The cytotoxicity study and apoptosis assay of paclitaxel-loaded liposomes showed that tri-Bio-Lip had the strongest anti-proliferative effect on breast cancer cells. The cellular uptake studies on mice breast cancer cells (4T1) and human breast cancer cells (MCF-7) indicated tri-Bio-Lip possessed the strongest internalization ability, which was 5.21 times of Lip, 2.60 times of Bio-Lip, 1.67 times of Bio-Bio-Lip and 1.17 times of tetra-Bio-Lip, respectively. Moreover, the 4T1 tumor-bearing BALB/c mice were used to evaluate the in vivo targeting ability. The data showed the enrichment of liposomes at tumor sites were tri-Bio-Lip > tetra-Bio-Lip > Bio-Bio-Lip > Bio-Lip > Lip, which were consistent with the results of in vitro targeting studies. In conclusion, increasing the density of targeting molecules on the surface of liposomes can effectively enhance the breast cancer targeting ability, and the branching structure and spatial distance of biotin residues may also have an important influence on the affinity to SMVT receptors. Therefore, tri-Bio-Lip could be a promising drug delivery system for targeting breast cancer.
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Affiliation(s)
- Baolan Tang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yao Peng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Qiming Yue
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yanchi Pu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Ru Li
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yi Zhao
- Department of Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Li Hai
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Li Guo
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
| | - Yong Wu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
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Core-shell lipid-polymer nanoparticles as a promising ocular drug delivery system to treat glaucoma. CHINESE CHEM LETT 2020. [DOI: 10.1016/j.cclet.2019.04.048] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Lipid Nanoarchitectonics for Natural Products Delivery in Cancer Therapy. SUSTAINABLE AGRICULTURE REVIEWS 2020. [DOI: 10.1007/978-3-030-41842-7_5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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25
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Chen F, Huang G. Application of glycosylation in targeted drug delivery. Eur J Med Chem 2019; 182:111612. [DOI: 10.1016/j.ejmech.2019.111612] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 07/26/2019] [Accepted: 08/09/2019] [Indexed: 01/10/2023]
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26
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Talaei S, Mellatyar H, Asadi A, Akbarzadeh A, Sheervalilou R, Zarghami N. Spotlight on 17-AAG as an Hsp90 inhibitor for molecular targeted cancer treatment. Chem Biol Drug Des 2019; 93:760-786. [PMID: 30697932 DOI: 10.1111/cbdd.13486] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 12/31/2018] [Accepted: 01/06/2019] [Indexed: 12/11/2022]
Abstract
Hsp90 is a ubiquitous chaperone with important roles in the organization and maturation of client proteins that are involved in the progression and survival of cancer cells. Multiple oncogenic pathways can be affected by inhibition of Hsp90 function through degradation of its client proteins. That makes Hsp90 a therapeutic target for cancer treatment. 17-allylamino-17-demethoxy-geldanamycin (17-AAG) is a potent Hsp90 inhibitor that binds to Hsp90 and inhibits its chaperoning function, which results in the degradation of Hsp90's client proteins. There have been several preclinical studies of 17-AAG as a single agent or in combination with other anticancer agents for a wide range of human cancers. Data from various phases of clinical trials show that 17-AAG can be given safely at biologically active dosages with mild toxicity. Even though 17-AAG has suitable pharmacological potency, its low water solubility and high hepatotoxicity could significantly restrict its clinical use. Nanomaterials-based drug delivery carriers may overcome these drawbacks. In this paper, we review preclinical and clinical research on 17-AAG as a single agent and in combination with other anticancer agents. In addition, we highlight the potential of using nanocarriers and nanocombination therapy to improve therapeutic effects of 17-AAG.
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Affiliation(s)
- Sona Talaei
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Mellatyar
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Asadollah Asadi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Abolfazl Akbarzadeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roghayeh Sheervalilou
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nosratollah Zarghami
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Abstract
INTRODUCTION Nanoparticles are under discussion in drug delivery for more than 20 years now, but examples for nanoparticulate formulations in the treatment of respiratory diseases are rare and mostly limited to the administration of sub-micron drug particles (ultrafine particles). However, nanoparticles may also carry specific benefits for respiratory treatment. Are nanoparticles the next-generation drug carrier system to facilitate systemic delivery, sustained release and cancer treatment in the lungs? AREAS COVERED This review will look into the promises and opportunities of the use of nanoparticles in the treatment of respiratory diseases. Important aspects to discuss are the fate of nanoparticles in the lung and mechanisms for reproducible delivery of nanoparticulate formulations to the lungs. Examples are given where nanoparticles may be advantageous over for traditional formulations and further aspects to explore are mentioned. EXPERT OPINION The benefit of nanoparticulate systems for respiratory delivery adds to the portfolio of possible formulation strategies, depends on the intended functionality and needs more exploration. Advantages of such systems are only seen in special cases.
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Affiliation(s)
- Regina Scherließ
- a Department of Pharmaceutics and Biopharmaceutics , Kiel University , Kiel , Germany
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Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomedicine 2017; 12:6997-7006. [PMID: 29033567 PMCID: PMC5614791 DOI: 10.2147/ijn.s145951] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Chronic liver diseases represent a global health problem due to their high prevalence worldwide and the limited available curative treatment options. They can result from various causes, both infectious and noninfectious diseases. The application of nanoparticle (NP) systems has emerged as a rapidly evolving area of interest for the safe delivery of various drugs and nucleic acids for chronic liver diseases. This review presents the pathogenesis, diagnosis and the emerging nanoparticulate systems used in the treatment of chronic liver diseases caused by liver fibrosis. Activated hepatic stellate cell (HSC) is considered to be the main mechanism for liver fibrosis. Ultrasonography and magnetic resonance imaging techniques are widely used noninvasive diagnostic methods for hepatic fibrosis. A variety of nanoparticulate systems are mainly focused on targeting HSC in the treatment of hepatic fibrosis. As early liver fibrosis is reversible by current NP therapy, it is being studied in preclinical as well as clinical trials. Among various nanoparticulate systems, inorganic NPs, liposomes and nanomicelles have been widely studied due to their distinct properties to deliver drugs as well as other therapeutic moieties. Liposomal NPs in clinical trials is considered to be a milestone in the treatment of hepatic fibrosis. Currently, NP therapy for liver fibrosis is updating fast, and hopefully, it can be the future remedy for liver fibrosis.
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Affiliation(s)
- Suchithra Poilil Surendran
- Department of Radiology, BioMolecular Theranostics (BiT) Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH), South Korea
| | - Reju George Thomas
- Department of Radiology, BioMolecular Theranostics (BiT) Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH), South Korea
| | - Myeong Ju Moon
- Department of Radiology, BioMolecular Theranostics (BiT) Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH), South Korea
| | - Yong Yeon Jeong
- Department of Radiology, BioMolecular Theranostics (BiT) Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH), South Korea
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Manatunga DC, de Silva RM, de Silva KN, de Silva N, Bhandari S, Yap YK, Costha NP. pH responsive controlled release of anti-cancer hydrophobic drugs from sodium alginate and hydroxyapatite bi-coated iron oxide nanoparticles. Eur J Pharm Biopharm 2017; 117:29-38. [DOI: 10.1016/j.ejpb.2017.03.014] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 03/04/2017] [Accepted: 03/17/2017] [Indexed: 11/27/2022]
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30
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Multifunctional near-infrared dye-magnetic nanoparticles for bioimaging and cancer therapy. Cancer Lett 2017; 390:168-175. [DOI: 10.1016/j.canlet.2016.12.026] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 12/18/2016] [Accepted: 12/20/2016] [Indexed: 02/07/2023]
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31
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Badri W, Miladi K, Nazari QA, Greige-Gerges H, Fessi H, Elaissari A. Encapsulation of NSAIDs for inflammation management: Overview, progress, challenges and prospects. Int J Pharm 2016; 515:757-773. [DOI: 10.1016/j.ijpharm.2016.11.002] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 10/17/2016] [Accepted: 11/01/2016] [Indexed: 12/20/2022]
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32
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Armendáriz-Barragán B, Zafar N, Badri W, Galindo-Rodríguez SA, Kabbaj D, Fessi H, Elaissari A. Plant extracts: from encapsulation to application. Expert Opin Drug Deliv 2016; 13:1165-75. [PMID: 27139509 DOI: 10.1080/17425247.2016.1182487] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Plants are a natural source of various products with diverse biological activities offering treatment for several diseases. Plant extract is a complex mixture of compounds, which can have antioxidant, antibiotic, antiviral, anticancer, antiparasitic, antifungal, hypoglycemic, anti-hypertensive and insecticide properties. The extraction of these extracts requires the use of organic solvents, which not only complicates the formulations but also makes it difficult to directly use the extracts for humans. To overcome these problems, recent research has been focused on developing new ways to formulate the plant extracts and delivering them safely with enhanced therapeutic efficacy. AREAS COVERED This review focuses on the research done in the development and use of polymeric nanoparticles for the encapsulation and administration of plant extracts. It describes in detail, the different encapsulation techniques, main physicochemical characteristics of the nanoparticles, toxicity tests and results obtained from in vivo or in vitro assays. EXPERT OPINION Major obstacles associated with the use of plant extracts for clinical applications include their complex composition, toxicity risks and extract instability. It is observed that encapsulation can be successfully used to decrease plant extracts toxicity, to provide targeted drug delivery and to solve stability related problems.
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Affiliation(s)
- Brenda Armendáriz-Barragán
- a Departamento de Química Analítica, Facultad de Ciencias Biológicas , Universidad Autónoma de Nuevo León , San Nicolás de los Garza , México.,b Laboratoire d'Automatique et des Génie des Procédés (ESCPE, CNRS UMR 5007) , Université Claude Bernard Lyon I , Villeurbanne , France
| | - Nadiah Zafar
- b Laboratoire d'Automatique et des Génie des Procédés (ESCPE, CNRS UMR 5007) , Université Claude Bernard Lyon I , Villeurbanne , France
| | - Waisudin Badri
- b Laboratoire d'Automatique et des Génie des Procédés (ESCPE, CNRS UMR 5007) , Université Claude Bernard Lyon I , Villeurbanne , France
| | - Sergio Arturo Galindo-Rodríguez
- a Departamento de Química Analítica, Facultad de Ciencias Biológicas , Universidad Autónoma de Nuevo León , San Nicolás de los Garza , México
| | - Dounia Kabbaj
- c Department of Agronomy and Life Science, Universiapolis , International University of Agadir , Agadir , Morocco
| | - Hatem Fessi
- b Laboratoire d'Automatique et des Génie des Procédés (ESCPE, CNRS UMR 5007) , Université Claude Bernard Lyon I , Villeurbanne , France
| | - Abdelhamid Elaissari
- b Laboratoire d'Automatique et des Génie des Procédés (ESCPE, CNRS UMR 5007) , Université Claude Bernard Lyon I , Villeurbanne , France
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Rostami I, Zhao Z, Wang Z, Zhang W, Zhong Y, Zeng Q, Jia X, Hu Z. Peptide-conjugated PEGylated PAMAM as a highly affinitive nanocarrier towards HER2-overexpressing cancer cells. RSC Adv 2016. [DOI: 10.1039/c6ra19552k] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Efficient drug delivery to the tumor cells was carried out with HER2 targeting peptide-conjugated PEGlyted PAMAM.
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Affiliation(s)
- Iman Rostami
- CAS Center for Excellents for Nanoscience
- National Center for Nanoscience and Technology
- Beijing 100190
- China
- University of Chinese Academy of Sciences
| | - ZiJian Zhao
- CAS Center for Excellents for Nanoscience
- National Center for Nanoscience and Technology
- Beijing 100190
- China
- University of Chinese Academy of Sciences
| | - ZiHua Wang
- CAS Center for Excellents for Nanoscience
- National Center for Nanoscience and Technology
- Beijing 100190
- China
- University of Chinese Academy of Sciences
| | - WeiKai Zhang
- CAS Center for Excellents for Nanoscience
- National Center for Nanoscience and Technology
- Beijing 100190
- China
- Henan University of Science & Technology
| | - Yeteng Zhong
- CAS Center for Excellents for Nanoscience
- National Center for Nanoscience and Technology
- Beijing 100190
- China
| | - Qiang Zeng
- Health Management Institute
- Chinese PLA General Hospital
- China
| | - XinRu Jia
- Department of Polymer Science and Engineering and Key Laboratory of Polymer Chemistry and Physics of the Ministry of Education
- College of Chemistry and Molecular Engineering
- Peking University
- Beijing
- China
| | - ZhiYuan Hu
- CAS Center for Excellents for Nanoscience
- National Center for Nanoscience and Technology
- Beijing 100190
- China
- Institute for Systems Biology
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Nakamura H, Abu Lila AS, Nishio M, Tanaka M, Ando H, Kiwada H, Ishida T. Intra-tumor distribution of PEGylated liposome upon repeated injection: No possession by prior dose. J Control Release 2015; 220:406-413. [PMID: 26548975 DOI: 10.1016/j.jconrel.2015.11.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 10/12/2015] [Accepted: 11/04/2015] [Indexed: 01/26/2023]
Abstract
Liposomes have proven to be a viable means for the delivery of chemotherapeutic agents to solid tumors. However, significant variability has been detected in their intra-tumor accumulation and distribution, resulting in compromised therapeutic outcomes. We recently examined the intra-tumor accumulation and distribution of weekly sequentially administered oxaliplatin (l-OHP)-containing PEGylated liposomes. In that study, the first and second doses of l-OHP-containing PEGylated liposomes were distributed diversely and broadly within tumor tissues, resulting in a potent anti-tumor efficacy. However, little is known about the mechanism underlying such a diverse and broad liposome distribution. Therefore, in the present study, we investigated the influence of dosage interval on the intra-tumor accumulation and distribution of "empty" PEGylated liposomes. Intra-tumor distribution of sequentially administered "empty" PEGylated liposomes was altered in a dosing interval-dependent manner. In addition, the intra-tumor distribution pattern was closely related to the chronological alteration of tumor blood flow as well as vascular permeability in the growing tumor tissue. These results suggest that the sequential administrations of PEGylated liposomes in well-spaced intervals might allow the distribution to different areas and enhance the total bulk accumulation within tumor tissue, resulting in better therapeutic efficacy of the encapsulated payload. This study may provide useful information for a better design of therapeutic regimens involving multiple administrations of nanocarrier drug delivery systems.
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Affiliation(s)
- Hiroyuki Nakamura
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan
| | - Amr S Abu Lila
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Miho Nishio
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan
| | - Masao Tanaka
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan
| | - Hidenori Ando
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan
| | - Hiroshi Kiwada
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan
| | - Tatsuhiro Ishida
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan.
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35
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Chitosan coatings to control release and target tissues for therapeutic delivery. Ther Deliv 2015; 6:855-71. [DOI: 10.4155/tde.15.31] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The natural biopolymer chitosan has versatile applications in therapeutic delivery. Coating drug delivery matrices or biomaterials with chitosan offers several advantages in drug delivery, including control of drug release, slowing degradation rate and improving biocompatibility. Advanced uses of chitosan in coating form include targeting drug delivery vehicles to specific tissue as well as providing a stimulus-controlled release response. The present review summarizes the current applications of chitosan coatings in the context of different biomaterial delivery technologies, as well as future directions of chitosan coatings for drug delivery technologies under development.
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36
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Valero J, Shiraishi T, de Mendoza J, Nielsen PE. Cellular Antisense Activity of PNA-Oligo(bicycloguanidinium) Conjugates Forming Self-Assembled Nanoaggregates. Chembiochem 2015; 16:1593-600. [PMID: 26010253 DOI: 10.1002/cbic.201500172] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Indexed: 12/12/2022]
Abstract
A series of peptide nucleic acid-oligo(bicycloguanidinium) (PNA-BGn ) conjugates were synthesized and characterized in terms of cellular antisense activity by using the pLuc750HeLa cell splice correction assay. PNA-BG4 conjugates exhibited low micromolar antisense activity, and their cellular activity required the presence of a hydrophobic silyl terminal protecting group on the oligo(BG) ligand and a minimum of four guanidinium units. Surprisingly, a nonlinear dose-response with an activity threshold around 3-4 μM, indicative of large cooperativity, was observed. Supported by light scattering and electron microscopy analyses, we propose that the activity, and thus cellular delivery, of these lipo-PNA-BG4 conjugates is dependent on self-assembled nanoaggregates. Finally, cellular activity was enhanced by the presence of serum. Therefore we conclude that the lipo-BG-PNA conjugates exhibit an unexpected mechanism for cell delivery and are of interest for further in vivo studies.
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Affiliation(s)
- Julián Valero
- Institute of Chemical Research of Catalonia. nt Avgda. Països Catalans 16, 43007 Tarragona (Spain).,Present address: LIMES Institute, Chemical Biology and Medicinal Chemistry Unit c/o Kekulé Institute of Organic Chemistry and Biochemistry, Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
| | - Takehiko Shiraishi
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, 2200 Copenhagen N (Denmark)
| | - Javier de Mendoza
- Institute of Chemical Research of Catalonia. nt Avgda. Països Catalans 16, 43007 Tarragona (Spain)
| | - Peter E Nielsen
- Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, 2200 Copenhagen N (Denmark).
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Sharma S, Verma A, Teja BV, Pandey G, Mittapelly N, Trivedi R, Mishra PR. An insight into functionalized calcium based inorganic nanomaterials in biomedicine: Trends and transitions. Colloids Surf B Biointerfaces 2015; 133:120-39. [PMID: 26094145 DOI: 10.1016/j.colsurfb.2015.05.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 05/06/2015] [Accepted: 05/08/2015] [Indexed: 12/28/2022]
Abstract
Over the recent years the use of biocompatible and biodegradable nanoparticles in biomedicine has become a significant priority. Calcium based ceramic nanoparticles like calcium phosphate (CaP) and calcium carbonate (CaCO3) are therefore considered as attractive carriers as they are naturally present in human body with nanosize range. Their application in tissue engineering and localized controlled delivery of bioactives for bones and teeth is well established now, but recently their use has increased significantly as carrier of bioactives through other routes also. These delivery systems have become most potential alternatives to other commonly used delivery system because of their cost effectiveness, biodegradability, chemical stability, controlled and stimuli responsive behaviour. This review comprehensively covers their characteristic features, method of preparation and applications but the thrust is to focus their recent development, functionalization and use in systemic delivery. On the same platform mineralization of other nanoparticulate delivery system which has widened their application drug delivery will be discussed. The emphasis has been given on their pH dependent properties which make them excellent carriers for tumour targeting and intracellular delivery. Finally this review also attempts to discuss their drawback which limits their clinical utility.
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Affiliation(s)
- Shweta Sharma
- Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India
| | - Ashwni Verma
- Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India
| | - B Venkatesh Teja
- Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India
| | - Gitu Pandey
- Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India
| | - Naresh Mittapelly
- Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India
| | - Ritu Trivedi
- Division of Endocrinology, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India
| | - P R Mishra
- Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India.
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Wang D, Tu C, Su Y, Zhang C, Greiser U, Zhu X, Yan D, Wang W. Supramolecularly engineered phospholipids constructed by nucleobase molecular recognition: upgraded generation of phospholipids for drug delivery. Chem Sci 2015; 6:3775-3787. [PMID: 29218147 PMCID: PMC5707505 DOI: 10.1039/c5sc01188d] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 05/11/2015] [Indexed: 12/14/2022] Open
Abstract
Supramolecularly engineered phospholipids and liposomes based on complementary hydrogen bonding of nucleosides have been developed.
Despite of great advances of phospholipids and liposomes in clinical therapy, very limited success has been achieved in the preparation of smart phospholipids and controlled-release liposomes for in vivo drug delivery and clinical trials. Here we report a supramolecular approach to synthesize novel supramolecularly engineered phospholipids based on complementary hydrogen bonding of nucleosides, which greatly reduces the need of tedious chemical synthesis, including reducing the strict requirements for multistep chemical reactions, and the purification of the intermediates and the amount of waste generated relative more traditional approaches. These upgraded phospholipids self-assemble into liposome-like bilayer structures in aqueous solution, exhibiting fast stimuli-responsive ability due to the hydrogen bonding connection. In vitro and in vivo evaluations show the resulted supramolecular liposomes from nucleoside phospholipids could effectively transport drug into tumor tissue, rapidly enter tumor cells, and controllably release their payload in response to an intracellular acidic environment, thus resulting in a much higher antitumor activity than conventional liposomes. The present supramolecularly engineered phospholipids represent an important evolution in comparison to conventional covalent-bonded phospholipid systems.
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Affiliation(s)
- Dali Wang
- School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . ; ; Tel: +86-21-34203400
| | - Chunlai Tu
- School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . ; ; Tel: +86-21-34203400
| | - Yue Su
- School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . ; ; Tel: +86-21-34203400
| | - Chuan Zhang
- School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . ; ; Tel: +86-21-34203400
| | - Udo Greiser
- Charles Institute of Dermatology , School of Medicine and Medical Science , University College Dublin , Belfield , Dublin 4 , Ireland .
| | - Xinyuan Zhu
- School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . ; ; Tel: +86-21-34203400
| | - Deyue Yan
- School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . ; ; Tel: +86-21-34203400
| | - Wenxin Wang
- Charles Institute of Dermatology , School of Medicine and Medical Science , University College Dublin , Belfield , Dublin 4 , Ireland .
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Abstract
Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential.
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Affiliation(s)
- Fabian Kiessling
- From the Department of Experimental Molecular Imaging, RWTH-Aachen University, Aachen, Germany (F.K., M.E.M., T.L.); and Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY (J.G.)
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Xu Z, Liu S, Wang H, Gao G, Yu P, Chang Y. Encapsulation of iron in liposomes significantly improved the efficiency of iron supplementation in strenuously exercised rats. Biol Trace Elem Res 2014; 162:181-8. [PMID: 25296704 DOI: 10.1007/s12011-014-0143-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 09/29/2014] [Indexed: 12/13/2022]
Abstract
To investigate the effect of iron liposome supplementation, a rat model of exercise-associated anemia was established by subjecting the animals to high-intensity running exercises for 4 weeks. Rats with confirmed anemia were strenuously exercised for another 2 weeks while receiving iron supplements by intragastric administration of ferric ammonium citrate (FAC) liposomes or heme iron liposomes. Control groups were administered equivalent amounts of FAC, heme iron, or blank liposomes. Subsequently, complete blood count (CBC), serum iron, and liver iron levels were tested to determine the efficiency of iron liposomes in relieving anemia. Superoxide dismutase (SOD) and malonyldialdehyde (MDA) were also detected to determine potential side effects of iron supplementation. The CBC, as well as serum iron and liver iron contents, significantly increased and reached much higher levels in anemic rats treated with iron liposomes, compared with those of control groups. The increase of SOD and decrease of MDA levels were also observed after supplementation with iron liposomes. These results demonstrate that iron liposomes can efficiently relieve the iron deficiency in strenuously exercised rats and may potentially be used as a supplement for the treatment of exercise-associated iron deficiency anemia with minimal side effects.
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Affiliation(s)
- Zi Xu
- Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Normal University, Shijiazhuang, 050024, Hebei Province, People's Republic of China
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Fu YC, Fu TF, Wang HJ, Lin CW, Lee GH, Wu SC, Wang CK. Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation. Acta Biomater 2014; 10:4583-4596. [PMID: 25050775 DOI: 10.1016/j.actbio.2014.07.015] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 07/05/2014] [Accepted: 07/14/2014] [Indexed: 12/27/2022]
Abstract
Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone-targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected to enable the transport of hydrophobic drugs. The molecular structures were examined by (1)H NMR or identified using mass spectrometry and Fourier transform infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent displacement method, and their size characteristics were evaluated using transmission electron microscopy (TEM) and dynamic light scattering. The bone targeting potential of the NP was evaluated in vitro using hydroxyapatite affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It was confirmed that the average particle size of the NP was <200 nm and that the dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral binding ability. Preliminary findings in vivo bone affinity assays in zebrafish and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3 moiety. These NP may act as a delivery system for hydrophobic drugs, warranting further evaluation of the treatment of bone disease.
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Affiliation(s)
- Yin-Chih Fu
- Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tzu-Fun Fu
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Jen Wang
- Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
| | - Che-Wei Lin
- Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
| | - Gang-Hui Lee
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shun-Cheng Wu
- Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Kuang Wang
- Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
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42
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Ritwiset A, Krongsuk S, Johns J. Molecular structure and stability of the sorbitan monostearate (Span60) monolayers film at the water–air interface: A molecular dynamics simulation study. J Mol Liq 2014. [DOI: 10.1016/j.molliq.2014.02.032] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Giannitrapani L, Soresi M, Bondì ML, Montalto G, Cervello M. Nanotechnology applications for the therapy of liver fibrosis. World J Gastroenterol 2014; 20:7242-7251. [PMID: 24966595 PMCID: PMC4064070 DOI: 10.3748/wjg.v20.i23.7242] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Accepted: 03/06/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and, in the more advanced stages, for the limited available curative treatment options. In fact, when lesions of different etiologies chronically affect the liver, triggering the fibrogenesis mechanisms, damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications, expensive treatments and death in end-stage liver disease. Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis, the drugs used in liver fibrosis treatment still have a limited therapeutic effect. Many drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are affected. Hepatic stellate cells play a critical role in liver fibrogenesis , thus they are the target cells of antifibrotic therapy. The application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents (including drugs and nucleic acid) in the treatment of various pathologies, including liver disease. In this review, we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.
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Pritz CO, Dudás J, Rask-Andersen H, Schrott-Fischer A, Glueckert R. Nanomedicine strategies for drug delivery to the ear. Nanomedicine (Lond) 2014; 8:1155-72. [PMID: 23837855 DOI: 10.2217/nnm.13.104] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The highly compartmentalized anatomy of the ear aggravates drug delivery, which is used to combat hearing-related diseases. Novel nanosized drug vehicles are thought to overcome the limitations of classic approaches. In this article, we summarize the nanotechnology-based efforts involving nano-objects, such as liposomes, polymersomes, lipidic nanocapsules and poly(lactic-co-glycolic acid) nanoparticles, as well as nanocoatings of implants to provide an efficient means for drug transfer in the ear. Modern strategies do not only enhance drug delivery efficiency, in the inner ear these vector systems also aim for specific uptake into hair cells and spiral ganglion neurons. These novel peptide-mediated strategies for specific delivery are reviewed in this article. Finally, the biosafety of these vector systems is still an outstanding issue, since long-term application to the ear has not yet been assessed.
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Affiliation(s)
- Christian Oliver Pritz
- Department of Otolaryngology, Medical University of Innsbruck, Innsbruck, Anichstraße 35, Austria
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Mishra D, Hubenak JR, Mathur AB. Nanoparticle systems as tools to improve drug delivery and therapeutic efficacy. J Biomed Mater Res A 2013; 101:3646-60. [PMID: 23878102 DOI: 10.1002/jbm.a.34642] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2012] [Revised: 02/04/2013] [Accepted: 02/05/2013] [Indexed: 02/03/2023]
Abstract
Nanoparticle-based drug delivery systems are appealing because, among other properties, they are easily manufactured and have the capacity to encapsulate a wide variety of drugs, many of which are not directly miscible with water. This review classifies nanoparticles into three broad categories based upon material composition: bio-inspired systems, synthetic systems, and inorganic systems. Each has distinct properties suitable for drug delivery applications, including their structure, composition, and pharmacokinetics (including clearance and uptake mechanisms), making each uniquely suitable for certain types of drugs. Furthermore, nanoparticles can be customized, making them ideal for a variety of applications. Advantages and disadvantages of the different systems are discussed. Strategies for improving nanoparticle efficacy include adding targeting agents on the nanoparticle surface, altering the degradation profile to control drug release, or PEGylating the surface to increase circulation times and reduce immediate clearance by the kidneys. The future of nanoparticle systems seems to be focused on further improving overall patient outcome by increasing delivery accuracy to the target area.
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Affiliation(s)
- Deepa Mishra
- Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 602, Houston, Texas, 77030
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Ding H, Wu F, Nair MP. Image-guided drug delivery to the brain using nanotechnology. Drug Discov Today 2013; 18:1074-80. [PMID: 23817076 PMCID: PMC4186772 DOI: 10.1016/j.drudis.2013.06.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Revised: 06/03/2013] [Accepted: 06/19/2013] [Indexed: 12/24/2022]
Abstract
Targeting across the blood-brain barrier (BBB) for treatment of central nervous system (CNS) diseases represents the most challenging aspect of, as well as one of the largest growing fields in, neuropharmaceutics. Combining nanotechnology with multiple imaging techniques has a unique role in the diagnosis and treatment (theranostics) of CNS disease. Such imaging techniques include anatomical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound (US), X-ray computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT), electron microscopy, autoradiography and optical imaging as well as thermal images. In this review, we summarize and discuss recent advances in formulations, current challenges and possible hypotheses concerning the use of such theranostics across the BBB.
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Affiliation(s)
- Hong Ding
- Department of Immunology, College of Medicine, Florida International University, Miami, FL 33199, USA
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Controlling the actuation of therapeutic nanomaterials: enabling nanoparticle-mediated drug delivery. Ther Deliv 2013; 4:1411-29. [DOI: 10.4155/tde.13.110] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The implementation of biofunctionalized nanoparticles (NPs) as potential therapeutic materials has seen exponential growth in recent years due to their unique ability to overcome the constraints of current medicine. This has been largely driven by significant advances on a number of basic research fronts including high-quality NP synthesis, bioconjugation, cellular delivery and the controlled release or ‘actuation’ of NP-associated cargos. Cumulatively, these are the key enabling tools for the full realization of NP-mediated drug delivery. In this review, the authors’ focus is on recent developments in methodologies for the controlled actuation of therapeutic NPs. The authors discuss the critical requirements for their integration into biological systems and highlight examples from the recent literature where controlled NP actuation has been successfully demonstrated. The current state of therapeutic NPs in the clinical setting is summarized and the article concludes with a brief perspective of how we can expect to see this emerging field develop in the coming years.
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Abstract
Cap analogs are chemically modified derivatives of the unique cap structure present at the 5´ end of all eukaryotic mRNAs and several non-coding RNAs. Until recently, cap analogs have served primarily as tools in the study of RNA metabolism. Continuing advances in our understanding of cap biological functions (including RNA stabilization, pre-mRNA splicing, initiation of mRNA translation, as well as cellular transport of mRNAs and snRNAs) and the consequences of the disruption of these processes - resulting in serious medical disorders - have opened new possibilities for pharmaceutical applications of these compounds. In this review, the medicinal potential of cap analogs in areas, such as cancer treatment (including eIF4E targeting and mRNA-based immunotherapy), spinal muscular atrophy treatment, antiviral therapy and the improvement of the localization of nucleus-targeting drugs, are highlighted. Advances achieved to date, challenges, plausible solutions and prospects for the future development of cap analog-based drug design are described.
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Chan KWY, Bulte JWM, McMahon MT. Diamagnetic chemical exchange saturation transfer (diaCEST) liposomes: physicochemical properties and imaging applications. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2013; 6:111-24. [PMID: 24339357 DOI: 10.1002/wnan.1246] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Chemical exchange saturation transfer (CEST) is a new type of magnetic resonance imaging (MRI) contrast based on labile spins which rapidly exchange with solvent, resulting in an amplification of signal which allows detection of solute protons at millimolar to micromolar concentrations. An additional feature of these agents is that natural organic and biodegradable compounds can provide strong CEST contrast, allowing the development of diamagnetic CEST (diaCEST) MRI contrast agents. The sensitivity of the CEST approach per unit of agent increases further when diaCEST contrast agents are loaded into liposomes to become diaCEST liposomes. In this review, we will discuss the unique and favorable features of diaCEST liposomes which are well suited for in vivo imaging. diaCEST liposomes are nanocarriers which feature high concentrations of encapsulated contrast material, controlled release of payload, and an adjustable coating for passive or active tumor targeting. These liposomes have water permeable bilayers and both the interior and exterior can be fine-tuned for many biomedical applications. Furthermore, a number of liposome formulations are used in the clinic including Doxil™, which is an approved product for treating patients with cancer for decades, rapid translation of these materials can be envisaged. diaCEST liposomes have shown promise in imaging of cancer, and monitoring of chemotherapy and cell transplants. The unique features of diaCEST liposomes are discussed to provide an overview of the applications currently envisioned for this new technology and to provide an overall insight of their potential.
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Affiliation(s)
- Kannie W Y Chan
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA
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IR-780 dye loaded tumor targeting theranostic nanoparticles for NIR imaging and photothermal therapy. Biomaterials 2013; 34:6853-61. [DOI: 10.1016/j.biomaterials.2013.05.071] [Citation(s) in RCA: 289] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 05/27/2013] [Indexed: 12/21/2022]
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