环孢素A海藻酸盐缓释微球的制备及体外释放

Preparation and in vitro release of cyclosporine A alginate slow release microspheres

针对角膜移植术后免疫排斥治疗研究背景,以多肽类免疫抑制剂环孢素A为药物模型,以海藻酸钠为载体材料,以辛癸酸甘油酯和Tween20为添加剂,采用脉冲电场工艺制备药物控释微球载体,对制备工艺参数进行正交设计优化。载药微球最佳制备处方为海藻酸钠质量分数0.8%、油水体积比1∶1.5、Tween20质量分数6.5%、环孢素A投药量65 mg。载药微球球型度优良,平均粒径(36.344±0.103)μm,粒径分布跨距2.314,药物包封率(86.03±0.65)%。在符合漏槽条件的人工泪液中,7 d累积释放率为56.5%,既能满足手术局部对药物浓度需求,又具有良好缓释性能。

Aiming at immune rejection study after corneal transplantation,with cyclosporine A as immunosuppressive drug model,sodium alginate as carrier material,and medium chain triglyceride（MCT） and Tween20 as additives,a kind of controlled release microspheres loaded cyclosporine A was prepared by pulse electostastic droplet generation technology.The process parameters were optimized with orthogonal design.The optimized parameters determined are as follows： sodium alginate mass fraction is 0.8%,volume ratio of water to medium chain triglyceride（MCT） is 1∶1.5,Tween20 mass fraction is 6.5% and cyclosporine A dosage is 65 mg.The morphology of CsA-loaded microspheres shows satisfied spherical shape.The mean particle size of drug-loaded microspheres is（36.344 ± 0.103） μm,size distribution span is 2.314,and the encapsulated rate of drug is（86.03±0.65）%.With simulated tears that are conformed with drug-leaking conditions as in vitro release media,the CsA-loaded microspheres show satisfied controlled release properties with the result of 7 d cumulative release rate of 56.5%.