聚乙二醇化PPI树枝状聚合物的合成、表征及体内胰岛素安全缓释评价

Q2 Pharmacology, Toxicology and Pharmaceutics Drug Delivery Letters Pub Date : 2019-08-31 DOI:10.2174/2210303109666190401231920
A. Parashar, P. Patel, A. Gupta, N. Jain, B. Kurmi
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引用次数: 14

摘要

本研究旨在开发和探索聚乙二醇化聚(丙基亚胺)树状大分子用于抗糖尿病药物胰岛素的递送。本研究以乙二胺为核心,丙烯腈为扩展剂,通过连续Michael加成和穷尽酰胺化反应合成了4.0G的PPI树状大分子。两种不同的活化PEG片段被用于PPI树状大分子的聚乙二醇化。测定并比较了聚乙二醇化和非聚乙二醇化树突状体系的各种理化和生理参数(UV、IR、NMR、TEM、DSC)、药物包裹、药物释放、溶血毒性和血糖水平。PPI树状大分子的聚乙二醇化导致胰岛素在树突框架和聚乙二醇层的增溶,减少药物释放和溶血毒性,提高治疗效果,减少胰岛素的副作用。通过对白化大鼠的体外和血糖水平研究发现,这些系统适合于持续输送胰岛素,而不会产生任何明显的血液学紊乱。因此,用PEG分子修饰PPI树状大分子的表面是一种合适的方法,可以将其作为一种安全有效的纳米药物载体。
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Synthesis, Characterization andin vivoEvaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin
The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin.For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared.PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances.Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.
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来源期刊
Drug Delivery Letters
Drug Delivery Letters Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
CiteScore
1.70
自引率
0.00%
发文量
30
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