Recent advances in macromolecular prodrugs |
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| Institution: | 1. DSAPM Lab and PCFM Lab, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China;2. Guangdong Medical College, Dongguan 523808, China;1. Department of Epidemiology, Brown University, Providence, RI, USA;2. Center for Global Cardiometabolic Health, Brown University, Providence, RI, USA;3. National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China;4. Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin, China;5. Department of Endocrinology, Guangdong Provincial People''s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;6. Department of Epidemiology & Biostatistics, School of Public Health, Zhengzhou University, China;1. Shenyang Pharmaceutical University, Shenyang 110016, China;2. Zhuhai Tianxiangyuan Biotechnology and Development Co., Ltd., Zhuhai 519000, China;3. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China;1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;2. Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;3. Department of Organic Chemistry, School of Science, China Pharmaceutical University, Nanjing 211198, China |
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| Abstract: | Macromolecular prodrugs (MP) are high molar mass conjugates, typically carrying several copies of a drug or a drug combination, designed to optimize delivery of the drug, that is — its pharmacokinetics. From its advent several decades ago, design of MP has undergone significant development and established solid guidelines for engineering successful MP in terms of the choice of the polymer carrier, its molar mass, and the choice of the linkage between the drug and the polymer. This review provides a brief account of the state-of-the-art in the development of MP and details the advantages of these tools of drug delivery. We also identify the challenges that need to be further addressed and offer a view on what is currently being done towards these goals. Specifically, we focus on i) the design of high molar mass, main-chain degradable polymers as drug carriers; ii) drug delivery using endogenous macromolecules such as albumin; iii) the choice of biodegradable linkages for drug delivery, and iv) the emerging interest in delivery of short-lived gasotransmitters. With this analysis and presentation, we aim to spur broader interest into MP to facilitate academic and translational development of MP. |
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