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 the in 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.

国家重大新药创制科技重大专项（2009ZX09502-019）；陕西省教育厅产业培育项目（2010JC20）