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聚乳酸-羟基乙酸共聚物-聚乙二醇-羧基(PLGA-PEG-COOH)与明胶基微粒双递送系统的开发以及电子束灭菌对骨形态发生蛋白-2(BMP-2)和胰岛素样生长因子-1(IGF-1)控释的影响

Development of PLGA-PEG-COOH and gelatin-based microparticles dual delivery system and E-beam sterilization effects for controlled release of BMP-2 and IGF-1.

作者信息

Bai Yan, Moeinzadeh Seyedsina, Kim Sungwoo, Park Youngbum, Lui Elaine, Tan Hua, Zhao Weiling, Zhou Xiaobo, Yang Yunzhi Peter

机构信息

Department of Orthopaedic Surgery, Stanford University, CA, USA.

School of Pharmacy, Chongqing Medical University, Chongqing, China.

出版信息

Part Part Syst Charact. 2020 Oct;37(10). doi: 10.1002/ppsc.202000180. Epub 2020 Aug 18.

Abstract

The purpose of this study was to develop a PLGA-PEG-COOH- and gelatin-based microparticles (MPs) dual delivery system for release of BMP-2 and IGF-1. We made and characterized the delivery system based on its morphology, loading capacity, Encapsulation efficiency and release kinetics. Second, we examined the effects of electron beam (EB) sterilization on BMP-2 and IGF-1 loaded MPs and their biological effects. Third, we evaluated the synergistic effect of a controlled dual release of BMP-2 and IGF-1 on osteogenesis of MSCs. Encapsulation efficiency of growth factors into gelatin and PLGA-PEG-COOH MPs are in the range of 64.78% to 76.11%. E-beam sterilized growth factor delivery systems were effective in significantly promoting osteogenesis of MSCs, although E-beam sterilization decreased the bioactivity of growth factors in MPs by approximately 22%. BMP-2 release behavior from gelatin MPs/PEG hydrogel shows a faster release (52.7%) than that of IGF-1 from the PLGA-PEG-COOH MPs/PEG hydrogel (27.3%). The results demonstrate that the gelatin and PLGA-PEG-COOH MPs based delivery system could realize temporal release of therapeutic biomolecules by incorporating different growth factors into distinct microparticles. EB sterilization was an accessible method for sterilizing growth factors loaded carriers, which could pave the way for implementing growth factor delivery in clinical applications.

摘要

本研究的目的是开发一种基于聚乳酸-羟基乙酸共聚物-聚乙二醇-羧基(PLGA-PEG-COOH)和明胶的微粒(MPs)双递送系统,用于释放骨形态发生蛋白-2(BMP-2)和胰岛素样生长因子-1(IGF-1)。我们基于其形态、载药量、包封率和释放动力学对该递送系统进行了制备和表征。其次,我们研究了电子束(EB)灭菌对负载BMP-2和IGF-1的MPs及其生物学效应的影响。第三,我们评估了BMP-2和IGF-1的可控双释放对间充质干细胞(MSCs)成骨的协同作用。生长因子包封入微明胶和PLGA-PEG-COOH MPs中的包封率在64.78%至76.11%之间。电子束灭菌的生长因子递送系统在显著促进MSCs成骨方面是有效的,尽管电子束灭菌使MPs中生长因子的生物活性降低了约22%。明胶MPs/聚乙二醇水凝胶中BMP-2的释放行为显示出比PLGA-PEG-COOH MPs/聚乙二醇水凝胶中IGF-1的释放速度更快(52.7%)(27.3%)。结果表明,基于明胶和PLGA-PEG-COOH MPs的递送系统通过将不同生长因子掺入不同微粒中可实现治疗性生物分子的定时释放。电子束灭菌是一种可用于对负载生长因子的载体进行灭菌的方法,这可为在临床应用中实现生长因子递送铺平道路。

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