PLGA微球的制备及其用于脉冲给药的初步研究

目的：制备聚乳酸-羟基乙酸共聚物（PLGA）微球,并考察其用于脉冲式释药系统的可行性。方法：以牛血清白蛋白（BSA）为模型药物,用S/O/W（Solid-in-oil-in-water）法和S/O/O（Solid-in-oil-in-oil）法制备PLGA（75：25）和PLGA（50：50）微球,比较2种方法制备的微球的表面形态、包封率及载药量等,并考察2种微球的体外释放行为。结果：S/O/W法和S/O/O法制备的微球均圆整、无粘连、形态良好,但S/O/W法制备的微球表面较为平整,而S/O/O法表面均匀分布有较大的凹陷。S/O/W法制备的PLGA（75：25）和PLGA（50：50）微球包封率分别为（60.15±5.95）%、（49.50±3.69）%,载药量分别为（2.56±0.25）%、（2.10±0.16）%,10h内药物释放均为10%左右,而后随着聚合物的降解药物的释放量突然增加;S/O/O法所制微球包封率分别为（84.36±1.11）%、（77.94±1.42）%,载药量分别为（3.58±0.05）%、（3.31±0.06）%,24h内药物释放均可达50%左右,而后呈现较为平稳的释放行为。S/O/O法制备的微球包封率及载药量均较S/O/W法高;S/O/W法制备的PLGA微球药物释放呈现一定的脉冲行为,其中PLGA（75：25）微球体外释放行为受微球粒径的影响较大。结论：S/O/W法制备的PLGA微球具有一定的脉冲式释药效果,微球的粒径最好控制在120μm以下。

Preparation of PLGA Microsphere and Preliminary Study of Its Pulsatile Drug Delivery

OBJECTIVE：To prepare polylactic acid-glycolic acid copolymer（PLGA）microsphere,and to investigate its feasibility for pulsatile drug delivery systems.METHODS：Using bovine serum albumin（BSA） as model drug,S/O/W（Solid-in-oil-in-water）method and S/O/O（Solid-in-oil-in-oil）method were used to prepare PLGA（75：25）and PLGA（50：50）microspheres.The surface morphology of the microspheres,encapsulation efficiency and drug-loading amount were compared,and drug release behavior of two kinds of microspheres were investigated in vitro.RESULTS：The microspheres prepared by S/O/W and S/O/O method were rounded,with good shape and no adhension,but the surface of microspheres prepared by S/O/W method were relatively flat,and the surface of microspheres prepared by S/O/O method was evenly distributed in a large depression.The encapsulation efficiency of PLGA（75：25）and PLGA（50：50）microspheres prepared by S/O/W method were（60.15±5.95）% and（49.50± 3.69）%,drug-loading amount of them were（2.56±0.25）% and（2.10±0.16）%,about 10% of drug were released within 10 h,and then drug release suddenly increased with the degradation of the polymer.The encapsulation efficiency of PLGA microspheres prepared by S/O/O method were（84.36±1.11）% and（77.94±1.42）%,drug-loading amount of them were（3.58±0.05）% and（3.31±0.06）%,and about 50% of drug were released within 24 h,and then presented a stable release behavior.The encapsulation efficiency and drug-loading amount of microsphere prepared by S/O/O method were higher than S/O/W method.The drug release of PLGA microspheres prepared by S/O/W method presented certain pulse behavior,and release behavior of PLGA（75：25）microspheres in vitro was influenced by the particle size of microspheres.CONCLUSION：PLGA microspheres prepared by S/O/W method represent a certain pulse-release effect,and the particle size of microspheres is preferably controlled below 120 μm.