双乳化-凝胶法制备单分散海藻酸钙微球及其载BSA研究

采用双乳化-凝胶法制备了单分散的海藻酸钙凝胶微球,并通过正交试验系统考察了海藻酸钠浓度、氯化钙浓度、表面活性剂浓度、搅拌速度和油水比对海藻酸钙凝胶微球粒径及形貌的影响。在优化的条件下,制备出了平均粒径为4μm、单分散和球形度好的海藻酸钙凝胶微球。包埋模型药物牛血清白蛋白(BSA)的过程中,以去离子水作为洗涤液洗涤海藻酸钙微球时,BSA的包封率仅为13%左右;当水洗液的pH值为3.2时,BSA的包封率提高到66%左右,载药率可达16%,这是海藻酸钙pH值响应溶胀和BSA与海藻酸盐之间静电作用的结果。微球中BSA的体外释放曲线表明,该系统具有在模拟胃液中释药速率慢、释药量低、模拟肠液中释药迅速的特性。因此,双乳化-凝胶法制备海藻酸钙微球有望成为制备蛋白类药物控释制剂的一种新方法,以达到靶向快速给药的目的。

Fabrication of monodispersed calcium alginate microspheres by double-emulsion gelation method and study on its release characteristics of BSA

Double-emulsion gelation method was employed for the preparation of monodispersed calcium alginate microspheres.The effects of experimental conditions such as the concentration of sodium alginate,calcium chloride,emulsifying speed,the volume ration of organic phase to aqueous phase and emulsifier concentration on particle size and morphology were investi-gated.Monodispersed microspheres with ideal spherical in shape and mean diameter of 4μm were obtained under the optimized conditions.Encapsulation efficiency of the model protein BSA in the calcium alginate was about 13%.But when the pH value of the washing liquor was adjusted to 3.2,the BSA encapsulation efficiency was calculated to be 66% with the loading capacity of 16%.Subsequent release characteristics of the BSA from calcium alginate microspheres in vitro were investigated.The release studies showed that the BSA was released at low rate in simulated gastric fluid while a large amount of BSA was released from the microspheres in a short time in simulated intestinal fluid.These results suggest that the double-emulsion gelation is a promising method to prepare alginate microspheres in the development of solid dosage forms for the peroral protein delivery and targeted release.