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用于聚合物药物递送微芯片的生物相容性聚乳酸和聚乙醇酸均聚物及共聚物在体内和体外的降解速率差异

Differential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip.

作者信息

Grayson Amy C R, Voskerician Gabriela, Lynn Aaron, Anderson James M, Cima Michael J, Langer Robert

机构信息

Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

J Biomater Sci Polym Ed. 2004;15(10):1281-304. doi: 10.1163/1568562041959991.

Abstract

The biocompatibility and biodegradation rate of component materials are critical when designing a drug-delivery device. The degradation products and rate of degradation may play important roles in determining the local cellular response to the implanted material. In this study, we investigated the biocompatibility and relative biodegradation rates of PLA, PGA and two poly(lactic-co-glycolic acid) (PLGA) polymers of 50:50 mol ratio, thin-film component materials of a drug-delivery microchip developed in our laboratory. The in vivo biocompatibility and both in vivo and in vitro degradation of these materials were characterized using several techniques. Total leukocyte concentration measurements showed normal acute and chronic inflammatory responses to the PGA and low-molecular-weight PLGA that resolved by 21 days, while the normal inflammatory responses to the PLA and high-molecular-weight PLGA were resolved but at slower rates up to 21 days. These results were paralleled by thickness measurements of fibrous capsules surrounding the implants, which showed greater maturation of the capsules for the more rapidly degrading materials after 21 days, but less mature capsules of sustained thicknesses for the PLA and high-molecular-weight PLGA up to 49 days. Gel-permeation chromatography of residual polymer samples confirmed classification of the materials as rapidly or slowly degrading. These materials showed thinner fibrous capsules than have been reported for other materials by our laboratory and have suitable biocompatibility and biodegradation rates for an implantable drug-delivery device.

摘要

在设计药物递送装置时,组成材料的生物相容性和生物降解速率至关重要。降解产物和降解速率在决定局部细胞对植入材料的反应中可能起重要作用。在本研究中,我们调查了聚乳酸(PLA)、聚乙醇酸(PGA)以及两种摩尔比为50:50的聚乳酸-乙醇酸共聚物(PLGA)(我们实验室开发的药物递送微芯片的薄膜组成材料)的生物相容性和相对生物降解速率。使用多种技术对这些材料的体内生物相容性以及体内和体外降解情况进行了表征。全白细胞浓度测量显示,对PGA和低分子量PLGA有正常的急性和慢性炎症反应,在21天时消退,而对PLA和高分子量PLGA的正常炎症反应虽已消退,但在长达21天的时间里消退速度较慢。这些结果与植入物周围纤维囊厚度的测量结果一致,后者显示,对于降解较快的材料,21天后纤维囊更加成熟,而对于PLA和高分子量PLGA,在长达49天的时间里,纤维囊厚度持续,成熟度较低。残留聚合物样品通过凝胶渗透色谱法证实了这些材料可分为快速降解或缓慢降解。这些材料的纤维囊比我们实验室报道的其他材料更薄,并且对于可植入药物递送装置具有合适的生物相容性和生物降解速率。

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