Hernádez R M, Igartua M, Gascón A R, Calvo M B, Pedraz J L
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
Eur J Drug Metab Pharmacokinet. 1998 Apr-Jun;23(2):92-6. doi: 10.1007/BF03189321.
The aim of the present work was to study the release of a model protein, bovine serum albumin (BSA) encapsulated within biodegradable poly (D,L-lactide-co-glycolide) (PLGA) microspheres prepared by a modified solvent evaporation method using a double emulsion. These microspheres were characterized for size, morphology, surface adsorbed protein, encapsulation efficiency and release kinetics. Two types of in vitro assays were developed to evaluate the influence of shaking and the addition of surfactants on the release profile of encapsulated protein. Scanning electron microscopy (SEM) observation showed spherical and smooth surface particles, with a mean particle size of 20 microm and an encapsulation efficiency of 81%. Surface associated protein was about 25%. The in vitro release profile showed a biphasic pattern described by means of a biexponential equation. There was an initial burst effect due to the release of the protein adsorbed on the microsphere surface and a sustained release phase due to protein diffusion through the channels or pores formed in the polymer coat. The release obtained profiles in static and dynamic assays showed statistically significant differences in the amount of the released protein, whereas the release rate was not affected. The burst effect was 28.30+/-1.63% and 35.20+/-1.50% of the total encapsulated protein for the static and dynamic assays respectively. The addition of surfactants (SDS) to the release medium increased the rate and the amount of drug released. In both assays the value of the slow release rate constant, beta, was 0.029+/-0.002 days(-1) when the surfactant was added, and 0.017+/-0.0014 days(-1) in the samples without surfactant. It is believed that the surfactant leads to an increase in the microsphere surface polarity which allows channel and pore formation inside the polymer through which the protein diffuses easily.
本研究的目的是研究一种模型蛋白——牛血清白蛋白（BSA）的释放情况，该蛋白被包裹在通过改良溶剂蒸发法使用双乳液制备的可生物降解聚（D，L-丙交酯-共-乙交酯）（PLGA）微球中。对这些微球的尺寸、形态、表面吸附蛋白、包封率和释放动力学进行了表征。开发了两种体外试验来评估振荡和添加表面活性剂对包封蛋白释放曲线的影响。扫描电子显微镜（SEM）观察显示颗粒呈球形且表面光滑，平均粒径为20微米，包封率为81%。表面相关蛋白约为25%。体外释放曲线呈现双相模式，可用双指数方程描述。由于吸附在微球表面的蛋白释放，存在初始突释效应，以及由于蛋白通过聚合物包衣中形成的通道或孔隙扩散而产生的持续释放阶段。在静态和动态试验中获得的释放曲线显示，释放蛋白的量在统计学上有显著差异，而释放速率不受影响。静态和动态试验的突释效应分别为总包封蛋白的28.30±1.63%和35.20±1.50%。向释放介质中添加表面活性剂（SDS）可提高药物释放速率和释放量。在两种试验中，添加表面活性剂时缓释速率常数β的值为0.029±0.002天-1，未添加表面活性剂的样品中为0.017±0.0014天-1。据信，表面活性剂导致微球表面极性增加，从而使聚合物内部形成通道和孔隙，蛋白可通过这些通道和孔隙轻松扩散。
