SPG膜乳化法制备载蛋白的CA-gel/PLGA复合微球  

CA-gel/PLGA composite microspheres loaded protein by SPG membrane emulsification

作　　者：钟晨[1] 罗宇燕[2] 郭喆霏[2] 罗永梅[1] 张永明[2] 

机构地区：[1]中山大学药学院,广东广州510006 [2]中山大学附属第三医院药剂科,广东广州510630

出　　处：《中山大学学报（自然科学版）》2016年第5期96-102,共7页Acta Scientiarum Naturalium Universitatis Sunyatseni

基　　金：广东省医院药学研究基金资助项目(2015SW12)

摘　　要：采用SPG膜乳化法,在PLGA微球的制备基础上,利用Sa与Ca^(2+)螯合形成难溶于水的CA-gel原理,以粒径、载药量、包封率、体外释放行为等作为评价指标,研究制备载蛋白药物的CA-gel/PLGA复合微球的新工艺,并对比复合微球和PLGA微球的载药释药特性的差异。与PLGA微球相比,复合微球的载药量由6.94%增加至8.35%,包封率由62.47%增加至75.16%,突释率由42.32%下降至30.84%。复合微球在经历早期的突释之后以较为均匀的速度缓慢持续释放药物,与PLGA微球相比,2~40 d的累积释放量由31.76%增加至40.29%。两者的释药曲线均符合Peppas-Sahlin方程(R^2>0.99),表明释药机制是扩散和溶蚀协同作用。采用扫描电镜观察到复合微球的结构更为致密,表面孔洞数量及面积明显减小,将其冷冻切片后观察到近表面的孔洞较少,平面孔隙率及孔隙数量均减小。激光共聚焦结果显示,更多的蛋白药物被包裹在复合微球内部,其荧光强度明显增强。表明CA-gel/PLGA复合微球能有效提高载药量和包封率,降低突释率,使微球后期释药增加。Protein loaded CA-gel/PLGA composite microspheres were prepared by a novel SPG membrane emulsification method, which was modified from the traditional preparation method of PLGA microspheres. The formation of the sustained-release gel was based on the ionic interaction between Sa and calcium ion. The drug loading of composite microspheres was significantly increased from 6.94% to 8.35%, entrapment efficiency was increased from 62. 47% to 75.16%, and the burst release rate was declined from 42.32% to 30. 84%. Drug release test showed that nearly 40.29% of drug was continuously and steadily released from the composite mierospheres in 2 -40 days. The drug release curves were corresponded to Peppas-Sahlin equation （R^2 〉 0. 99） for both the traditional microspheres and composite microspheres, which means that the release mechanism was mainly diffusion and dissolution. The results from scanning electron microscopy and freezing microtomy demonstrated that the composite microspheres were more compact in structure, and its surface hole number and porosity were smaller than traditional PLGA microspheres. The enhanced fluorescence intensity was observed from the laser confocal scan microscopy, indicating that more protein drugs were wrapped inside composite microspheres. In conclusion, the CA-gel/PLGA composite microspheres can effectively increase drug loading and entrapment efficiency and reduce the burst release.

关 键 词：SPG膜乳化法 CA-gel/PLGA复合微球 包封率 突释 

分 类 号：R943[医药卫生—药剂学]