Huatan H, Collett J H, Attwood D
Department of Pharmacy, University of Manchester, UK.
J Microencapsul. 1995 Sep-Oct;12(5):557-67. doi: 10.3109/02652049509006786.
Microspheres with an entrapped protein were prepared from poly(epsilon-caprolactone) (PCL), and a novel ternary blend, comprising of high and low molecular weight PCL in combination with poloxamer 181, a triblock copolymer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide). The inclusion of low molecular weight PCL served to enhance phase mixing by a reduction in the molecular weight of the polymeric components. Encapsulation of the protein, bovine serum albumin, was possible using a water-in-oil-in-water multiple emulsion solvent evaporation technique. Microspheres prepared from unblended PCL were irregular and porous in nature. The presence of surface imperfections and macroscopic pores was attributable to the high rate of crystallization of the PCL polymer from solution. The inclusion of poloxamer 181 into the matrix retarded the rate of crystallization of the PCL, thereby enhancing particulate sphericity and regularity. Manipulation of the process parameters of blended microspheres provided a means of controlling the particle size and the entrapment efficiency of the protein. The influence of variables such as protein to polymer ratio, internal phase volume and emulsifier concentration in both the internal and external aqueous phases, on the properties of the microspheres was investigated. A mean particle size ranging from 10 to 42 microns could be achieved by altering the internal phase volume of the primary emulsion, whilst a high protein entrapment (11% w/w) was possible with a protein to polymer ratio of 1:4. Native-PAGE analysis of the entrapped protein indicated a maintenance of bulk structural integrity.
用聚(ε-己内酯)(PCL)制备了包封蛋白质的微球,并制备了一种新型三元共混物,该共混物由高分子量和低分子量的PCL与泊洛沙姆181(一种聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)的三嵌段共聚物)组成。低分子量PCL的加入通过降低聚合物组分的分子量来增强相混合。使用水包油包水多重乳液溶剂蒸发技术可以包封蛋白质牛血清白蛋白。由未共混的PCL制备的微球本质上是不规则且多孔的。表面缺陷和宏观孔隙的存在归因于PCL聚合物从溶液中的高结晶速率。在基质中加入泊洛沙姆181可延缓PCL的结晶速率,从而提高颗粒的球形度和规则性。对共混微球工艺参数的控制提供了一种控制蛋白质粒径和包封效率的方法。研究了蛋白质与聚合物比例、内相体积以及内、外水相中的乳化剂浓度等变量对微球性质的影响。通过改变初级乳液的内相体积可以实现平均粒径在10至42微米之间,而当蛋白质与聚合物比例为1:4时,蛋白质包封率较高(11% w/w)。对包封蛋白质的天然聚丙烯酰胺凝胶电泳分析表明其整体结构完整性得以维持。