注射用蜂毒多肽温度敏感型缓释凝胶的制备及体外释放研究

Preparation and release in vitro of melittin from injectable thermosensitive hydrogels

目的制备注射用蜂毒多肽的温度敏感型缓释凝胶制剂并对其体外释药进行考察。方法以新型温度敏感聚丙交酯乙交酯聚乙二醇嵌段共聚物(PLGAPEGPLGA)为载体材料制备注射用蜂毒多肽缓释凝胶制剂,采用福林酚试剂法测定制剂在磷酸盐缓冲溶液中(pH7.4)的体外释放度,并对体外释放数据用KorsmeyerPeppas方程进行拟合。结果蜂毒多肽体外持续释放36d,其释药速率随聚合物的质量分数增加而降低,且聚合物分子结构中丙交酯比例增大对释药速率几乎没有影响。蜂毒多肽从凝胶中的释放初期以扩散为主,体外释放行为符合KorsmeyerPeppas方程,后期为凝胶溶蚀和药物扩散结合的作用机制。结论注射用蜂毒多肽的温度敏感型缓释凝胶制剂制备工艺简便,药物释放达到预期要求,同时说明温度敏感PLGAPEGPLGA嵌段共聚物作为注射用缓释给药系统的载体材料具有很好的应用前景。

Objective To prepare and evaluate the injectable temperature responsive hydrogels for sustained release of melittin in vitro.Methods The novel temperature responsive poly (DL-lactide-co-glycolide-b-ethyleneglycol-b-DL-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) were used as the carriers of melittin sustained release injection.The release of melittin from the copolymer-based hydrogel in the phosphate buffer (pH7.4) was studied at 37 ℃ under agitation.Folin-phenol reagent method was used for the determination of melittin.The data of release in vitro were analyzed according to the theoretical model of Korsmeyer-Peppas.Results Melittin was released from the copolymer-based hydrogels over 36 days in vitro.The release mechanism of melittin is diffusion dominant initially followed by the combination of hydrogel erosion and diffusion.Conclusions These results indicat that the PLGA-b-PEG-b-PLGA copolymer-based hydrogel could be a promising platform for injectable controlled delivery of melittin.