嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1的pH和温度敏感性质及体外释药特性考察

目的 为嵌段共聚物磺胺甲嘧啶低聚物-聚-ε-己内酯-丙交酯-聚乙二醇-聚-ε-己内酯-丙交酯-磺胺甲嘧啶低聚物（sulfamerazine oligomers-poly(ε-caprolactone-co-DL-lactide-b-ethyleneglycol-b-ε-caprolactone-co-DL-lactide)-sulfamerazine oligomers,OSM₁-PCLA-PEG-PCLA-OSM1)作为缓控释给药系统的载体提供依据。方法 采用激光粒度仪对不同pH和温度下嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁胶束粒径大小、分布进行考察;通过表面张力和相转变温度测定对其临界胶束浓度和溶液-凝胶相转变行为进行考察;以5-氟尿嘧啶为模型药,通过透射电镜观察载药和空白共聚物胶束形态;采用物理混合法制备5-氟尿嘧啶载药水凝胶;采用HPLC法测定载药水凝胶中药物释放速率。结果 嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁胶束溶液具有pH和温度双重敏感的性质,在一定pH和温度条件下可发生溶液-凝胶相转变;5-氟尿嘧啶载药水凝胶体外释放可持续9 d,具有较好的缓释作用。结论 pH和温度双重敏感型嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁作为注射缓释给药系统载体材料具有良好的应用前景。

pH and temperature sensitive properties and drug release in vitro of OSM1-PCLA-PEG-PCLA-OSM1 block copolymer hydrogel

Objective To study the pH and temperature sensitive properties of sulfamerazine oligomers-poly(ε-caprolactone-co-DL-lactide-b-ethyleneglycol-b-ε-caprolactone-co-DL-lactide-sulfamerazine oligomers（OSM₁-PCLA-PEG-PCLA-OSM₁）block copolymer and evaluate sustained release effect of 5-fluorouracil release from the loaded hydrogel in vitro. Methods Particle size distribution under different pH values and temperatures and micelle solution morphology were studied by laser size detector and transmission electron microscope to verify copolymers micelle formation. Meanwhile, the critical micelle concentration and phase transition temperature as a function of pH and temperature was studied. 5-fluorouracil was chosen as a model drug to prepare the drug loaded hydrogel. The HPLC method was used to determine the drug release from the hydrogel. Results OSM₁-PCLA-PEG-PCLA-OSM₁ block copolymer solutions possess both pH and temperature sensitive characteristics with solution-gelatin transition at certain temperature and pH conditions. 5-fluorouracil was released from the hydrogel for 9 days. Conclusions pH and temperature sensitive OSM₁-PCLA-PEG-PCLA-OSM₁ block copolymer can be potential intelligent polymer materials for injectable sustained drug delivery system.