Igartua M, Hernández R M, Esquisabel A, Gascon 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.
J Microencapsul. 1997 May-Jun;14(3):349-56. doi: 10.3109/02652049709051138.
Poly(D,L-lactide-co-glycolide) microspheres containing BSA were prepared by a modified solvent evaporation method using a double emulsion. These microspheres were characterized for size, morphology, surface absorbed protein, encapsulation efficiency and release kinetics. The influence of two formulation variables (the procedure to obtain the first emulsions and the lyophilization of the microspheres once obtained) on the physical characteristics and release behaviour of the microspheres was also investigated. Sonicated microspheres were smooth and spherical, with a mean particle size of 20 microns and an encapsulation efficiency of 81%. When the first emulsion was prepared by vortex mixing the particles were irregular and porous, with a mean size of 31 microns and a lower encapsulation efficiency (56%). The sonication allows a more homogeneous emulsion as well as a lower percentage of albumin adsorbed on the surface. The in vitro release profile was described as a biexponential process with an initial burst effect due to the release of the protein adsorbed on the microsphere surface and a second sustained release phase due to protein diffusion through the channels or pores formed in the polymer coat. The release of BSA was dependent on the preparation method. The greatest burst release was found for microspheres formulated using the vortex mixer, 58% of the encapsulated protein was released during the first 24 h, whereas sonicated microspheres released 32.2%. This burst effect could be reduced by lyophilizing the microspheres following their preparation. The amount of protein released decreased to 28.3% and 51.6% in sonicated and non-sonicated microspheres respectively, when they were lyophilized.
采用双乳液法，通过改进的溶剂蒸发法制备了含有牛血清白蛋白（BSA）的聚（D，L-丙交酯-共-乙交酯）微球。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。还研究了两个配方变量（获得初乳的方法以及微球制备后冻干）对微球物理特性和释放行为的影响。超声处理的微球光滑呈球形，平均粒径为20微米，包封率为81%。当通过涡旋混合制备初乳时，颗粒不规则且多孔，平均尺寸为31微米，包封率较低（56%）。超声处理可使乳液更均匀，且表面吸附的白蛋白百分比更低。体外释放曲线被描述为双指数过程，由于微球表面吸附蛋白的释放而出现初始突释效应，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出现第二个持续释放阶段。BSA的释放取决于制备方法。使用涡旋混合器制备的微球突释最大，在最初24小时内释放了58%的包封蛋白，而超声处理的微球释放了32.2%。制备后冻干微球可降低这种突释效应。超声处理和未超声处理的微球冻干后，蛋白释放量分别降至28.3%和51.6%。
