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Exenatide-loaded microsphere/ thermosensitive hydrogel long-acting delivery system with high drug bioactivity
作者:Wang, PX (Wang, Puxiu) [1] ; Zhuo, XZ (Zhuo, Xuezhi) [1] ; Chu, W (Chu, Wei) [1] ; Tang, X (Tang, Xing) [1]
卷528
期1-2
页62-75
DOI10.1016/j.ijpharm.2017.05.069
出版时间AUG 7 2017
已索引2017-08-07
文献类型Article
摘要
A series of mixed hydrogels of PLGA-PEG-PLGA and PCLA-PEG-PCLA were synthesized, and investigated in terms of their critical micelle concentration, stability and thermosensitive properties. Also, some mixed hydrogel was selected to prepare Depot-gel-in-Ms-in-Matrix-gel system for the treatment of type 2 diabetes mellitus. Briefly, Exenatide (EXT) loaded hydrogels was encapsulated in PLGA microspheres (Ms) and further encapsulated into blank hydrogel. The mechanism of Exenatide release involved drug diffusion, hydrogel diffusion, PLGA erosion and mixed hydrogel erosion. The results showed that EXT release in vitro was at a sustained rate for 46 days, because it is controlled by the inner-deport-gel, the Ms matrix and the outer-Matrix-gel successively. No burst release or platform was observed due to the interception function and control function of the outer-Matrix-gel. The biological activity of EXT was protected, because the hydrophilic EXT molecules tend to distribute in the hydrophilic domain of the mixed hydrogel. In vivo, a single injection of Depot-gel-in-Ms-in-Matrix-gel allowed mice to maintain a stable blood glucose concentration and well-controlled body weight for 20 days. In addition, results of oral glucose tolerance test and Hematoxylin-Eosin staining demonstrated that triple-barrier Depot-gelin-Ms-in-Matrix-gel was a promising hydrophilic protein/polypeptide-loaded long-acting system with high drug bioactivity. (C) 2017 Elsevier B.V. All rights reserved.

关键词
作者关键词ExenatidePeptideHydrogelPLGA microspheresPolymeric micelles
Keywords PlusPCLA-PEG-PCLABIODEGRADABLE TRIBLOCK COPOLYMERTYPE-2 DIABETES-MELLITUSCONTROLLED-RELEASEPLGA MICROSPHERESMOLECULAR-WEIGHTPOLYMERIC NANOPARTICLESBIOMEDICAL APPLICATIONSDEGRADATION PROPERTIESINTRAVITREAL DELIVERY
作者信息
通讯作者地址
Tang, Xing
(通讯作者)
Shenyang Pharmaceut Univ, Coll Pharm, Dept Pharmaceut, Shenyang 10016, Liaoning, Peoples R China
地址
1 Shenyang Pharmaceut Univ, Coll Pharm, Dept Pharmaceut, Shenyang 10016, Liaoning, Peoples R China
电子邮件地址tanglab@126.com
类别/分类
研究方向Pharmacology & Pharmacy
引文主题
2 Chemistry
2.53 Polymers & Macromolecules
2.53.371 Hydrogels

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