改善蛋白质药物PELA控释微球释放性能的研究

Study on Improvement of Release Behavior of Protein Drugs from PELA Microspheres

开展了以乙酸乙酯(EA)与二氯甲烷(MC)的混合溶液为有机溶剂、以单甲氧基聚乙二醇-聚-DL-乳酸(PELA)为膜材的W／O／W复乳-分步固化法制备蛋白质药物控释微球的研究。为解决微球突释率高、且突释后的释药速度缓慢的问题,实现后期快速释放,以溶菌酶为模型蛋白,重点考察了膜材组成、内水相体积以及外水相盐浓度对微球释药速率的影响。结果表明,当外水相盐浓度增大至1.5％时可将释放率由22％提升至45％,是一种较好的加快微球释药速率的途径,因此可通过选择适当的外水相盐浓度,达到所期望的药物释药速率。

The microspheres for protein controlled release were prepared by W/O/W double emulsion-stepwise solidification method. Monomethoxypoly (ethylene glycol)-b-poly-DL-lactide (PELA) was used as the wall material, with ethyl acetate(EA) as organic solvent of oil phase,and lysozyme as model protein. In order to increase the release rate after the burst release, the effects of polymer composition, the volume of internal aqueous phase and the concentration of NaCl in external aqueous phase were investigated. It showed that the NaCl concentration in external aqueous phase affected the release rate apparently. It was found that when the concentration of NaCl increased from 0.9% to 1.5 % , the release rate increased from 22 % to 45 % after 40 days of release study. Therefore the desired protein release profile could be achieved by selecting suitable concentration of NaCl in external aqueous phase.