微球_温敏凝胶复合植入给药系统释药特征及模型.pdfVIP

第7卷 第3期 224 中国科技论文 CHINA SCIENCEPAPER 2012 年 3 月 微球/温敏凝胶复合植入给药系统的释药特征及模型 蒋国强，林 莹，孙佳丽，丁富新 （清华大学化工系，北京 100084 ） 摘 要：将载药微球分散在温敏凝胶中构成的复合埋植给药系统，可实现长期稳定给药。以载有纳曲酮的乳酸- 乙醇 酸共聚物(PLGA)微球与甲基纤维素温敏凝胶构成的释药系统为例，研究了药物在该系统中的释放动力学特征和模型。 结果表明复合系统中的释药主要受药物在微球中的释放控制；水凝胶改变了微球的存在环境，增加了水的扩散阻力， 使药物扩散系数减小，微球溶蚀速率降低，达到最大溶蚀速率的时间推迟，从而使释药速率降低并更加平稳。将上述 影响引入微球释药模型，建立了微球-凝胶系统释药模型，模拟结果和实验数据吻合较好。通过调整微球材料的相对分 子量和亲疏水性，实现了纳曲酮超过 60 d 的恒速释放。 关键词：药剂学；埋植给药；凝胶；微球；释药动力学 中图分类号：R 944；TQ314 文献标志码：A 文章编号：2095 －2783(2012)03 －0224 －6 Characterizing the drug release from the hydrogel drug delivery system incorporated with biodegradable microspheres Jiang Guoqiang ，Lin Ying ，Sun Jiali ，Ding Fuxin (Department of Chemical Engineering , Tsinghua University, Beijing 100084, China) Abstract: The injectable gelling drug delivery system incorporated with biodegradable microspheres has great potential in implanted drug delivery for long-term controlled drug release. We investigated drug release in vitro in a model system which was composed by naltrexone-loaded PLGA microspheres and thermosensitive hydrogel consisted of methylcellulose, polyethylene glycol, sodium citrate and sodium alginate. In the microspheres-hydrogel composite system, drug release was dominated by drug diffusion in microspheres. The hydrogel affected the porosity, erosion and degradation of the microspheres, which resulted in the smaller drug diffusion coefficient, lower erosion rate and prolonged period to reach the maximal erosion rate. Therefore, it reduced and stabilized the drug release rate. These