鲑鱼降钙素新型注射用温度敏感原位凝胶系统的构建及评价

目的构建鲑鱼降钙素新型注射用温度敏感原位凝胶系统并对其胶凝特性和降血钙效应进行评价。方法以泊洛沙姆F127为主要基质材料,复合使用泊洛沙姆F68,制备鲑鱼降钙素注射用温度敏感原位凝胶给药系统,以胶凝温度、胶凝时间、流变学、质构特性为考察指标,对该凝胶系统性质进行评价;采用大鼠眼眶取血,钙显色法监测体内血清钙离子浓度,对该凝胶系统降血钙效应进行研究。结果所制备的鲑鱼降钙素注射用温度敏感原位凝胶的胶凝温度为(35.3±1.3)℃,胶凝时间为(108.3±5.5)s,在25℃条件下为流动的液体,原位凝胶的黏度和黏滞力极低,方便注射给药,当温度增至37℃时能够迅速发生相转变,黏度和黏滞力等质构特性数据显著增加,成为具有一定胶凝强度的半固体;大鼠降血钙效应结果显示,该给药系统具有明显的缓释作用,其24 h时血钙浓度明显低于普通注射剂组,相对于普通注射剂的药理活性为138.6%。结论温度敏感原位凝胶用于鲑鱼降钙素的注射给药,是一种很有潜力的递送系统。

Preparation and characterization of a novel injectable thermosensitive in situ gel containing salmon calcitonin

Objective To prepare the thermosensitive in situ gel of salmon calcitonin for injection and evaluate the characteristics and hypocalcemic effect. Methods Poloxamer F127 and poloxamer F68 were used to prepare the thermosensitive gel of samon calcitonin. The characteristics of the gel, such as gelation temperature, gelation time, rheological behavior and texture characteristics, were evaluated. Blood samples were drawn from orbit in rats, and coloration methods were used to monitor serum calcium ion concentration in order to study in vivo drug release and the hypocalcemic effect. Results The gelation temperature of the salmon calcitonin-loaded in situ gel was （35.3 ± 1.3）℃, and the gelation time was （108.3 ± 5.5） s. The in situ gel, a fluid solution at 25 ℃, became semisolid quickly at 37 ℃ due to the fact the viscosity and mechanical parameters such as gel strength for gel was enhanced at 37℃. The in situ gel loading sCT clearly decreased serum calcium level in rats over a longer period of time as compared with the conventional injection indicating sustained characteristic in vivo, and produced 138.6%hypocalcemic efficacy relative to common injection. Conclusion The thermosensitive in situ gel delivery system may be a promising candidate for injectable sustained delivery of salmon calcitonin.