盐酸青藤碱关节腔注射用纳米粒温敏凝胶的制备及其性质考察

Preparation of sinomenine hydrochloride nanoparticle thermosensitive gel for intra-articular injection and its characteristic investigation

目的制备关节腔注射用盐酸青藤碱固体脂质纳米粒(盐酸青藤碱-SLN)温敏凝胶并考察其体外释放特征。方法以泊洛沙姆407(P-407)和泊洛沙姆188(P-188)为凝胶基质,以凝胶胶凝温度为考察对象对处方进行优化;微乳液法制备盐酸青藤碱-SLN,冷溶法制备盐酸青藤碱-SLN温敏凝胶;用HPLC法测定盐酸青藤碱的量,透析法研究盐酸青藤碱-SLN温敏凝胶的体外释放特性。结果最佳处方为18%P-407、5%P-188和0.6%羟丙基甲基纤维素(HPMC),所制盐酸青藤碱-SLN温敏凝胶胶凝温度为(34.5±0.2)℃。体外释放结果显示盐酸青藤碱-SLN温敏凝胶24 h内累积释放率为(57.79±0.36)%,48 h内累积释放率为(75.16±0.12)%,具有明显的缓释作用。结论所制盐酸青藤碱-SLN温敏凝胶具有温敏特性和明显的缓释作用,纳米载体和温度敏感凝胶的组合有望成为新的关节腔给药传递系统。

Objective To prepare the solid lipid nanoparticle（SLN） thermosensitive gel of sinomenine hydrochloride（SH） for intra-articular injection and to investigate its in vitro drug release behavior.Methods Poloxamer 407（P-407） and Poloxamer 188（P-188） were used as gel matrix to prepare the gel,and the gelatinization temperature was applied as a target to optimize the prescription.The SH-SLN was prepared based on the microemulsion technique,and the gel system containing SH-SLN was obtained by cold-dissolving methods.The content of SH was determined by HPLC,in vitro release characteristics of SH-SLN thermosensitive gel were investigated by dialysis method.Results The optimal gel prescription was finally confirmed as 18% P-407,5% P-188,and 0.6% HPMC.The gelatination temperature for SH-SLN thermosensitive gel was（34.5 ± 0.2） ℃,and thein vitro accumulated release rates of SH in the SLN thermosensitive gel system were（57.79 ± 0.36）% after 24 h and（75.16 ± 0.12）% after 48 h.Conclusion The SH-SLN thermosensitive gel has the temperature sensitivity and obvious sustained-release effect.The combination of nanoparticle thermosensitive gel will be used as a new drug delivery for intra-articular injection.