乳酸-羟基乙酸共聚物缓控释微球的制备及突释成因与影响因素

Preparation,burst release and influencing factors of poly(lactic-co-glycolic acid) microspheres

背景:乳酸-羟基乙酸共聚物是一种生物可降解高分子材料,以乳酸-羟基乙酸共聚物为原料制备的载药微球和纳米粒既可提高药物的稳定性,又能实现缓释、控释和靶向释放。目的:分析乳酸-羟基乙酸共聚物缓控释微球的制备方法以及突释的成因、影响因素和改进方法。方法:应用计算机检索1990/2010中国期刊全文数据库和PubMed数据库与乳酸-羟基乙酸共聚物缓控释微球的制备及突释联系紧密的文章。结果与结论:目前乳酸-羟基乙酸共聚物缓释微球制备方法主要有单凝聚法、乳化-固化法、喷雾干燥法。造成其突释的原因首先是药物分子和聚合物分子之间的相互作用太弱,导致药物很容易从微球进入释放递质中,其次是在微球释放初期,药物从微球中的孔洞和缝隙中释放出来导致突释。影响突释程度的具体因素有乳酸-羟基乙酸共聚物的相对分子质量、浓度、微球载药量、主药理化性质、微球制备方法及制备参数等。虽然国内外对突释机制以及控制突释措施的研究都还处于初步阶段,通过对各影响因素加以适当优化与控制,可在一定程度上减少微球的突释率,突释问题应该能够得到解决和控制。

BACKGROUND：Poly（lactic-co-glycolic acid） （PLGA） is a biocompatible polymer material. PLGA-based microspheres and nanoparticles can improve the stability of drugs,also achieve sustained release,controlled release and targeted release. OBJECTIVE：To analyze the methods in preparation of PLGA microparticles,and the cause,influencing factors and improvement methods of burst release. METHODS：A computer-based online research was performed in China Journal Full-text Database and PubMed database published from 1990 to 2010. Articles concerning the preparation and burst release of PLGA microparticles were included. RESULTS AND CONCLUSION：Currently the methods of preparing PLGA microparticles contain single coagulation,emulsification-curing,spray drying methods. The reasons causing the burst release is primarily a weak interaction between drug molecules and polymer molecules,easily leading to drug release from the microspheres into the release medium,then drug release from the microsphere holes and gaps at the early release stage,thus leading to burst release. The factors influencing burst release are PLGA molecular weight,concentration,drug loading of microspheres,main pharmacological and physico-chemical properties,preparation methods and preparation parameter of microspheres. Although many scholars are still primarily studying the underlying mechanism and controlling measures of burst release,it is believed to reduce the burst release rate of microspheres through proper optimization and control of the influencing factors,thus solving burst release problem.