载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶的制备与性能研究  

Preparation of Lappaconitine-Loaded Chitosan / Sodium β-Glycerophosphate Injectable Thermosensitive Hydrogels and Research on Its Properties

作　　者：马君义[1,2] 陈香玲[1] 盛爱霞 邱雅静 梁艳丽[1] 张继[1,2] 

机构地区：[1]西北师范大学生命科学学院,兰州730070 [2]甘肃特色植物有效成分制品工程技术研究中心,兰州730070

出　　处：《中国药学杂志》2015年第19期1696-1703,共8页Chinese Pharmaceutical Journal

基　　金：兰州市科技计划资助项目(2012-2-92)

摘　　要：目的制备载高乌甲素(LA)的壳聚糖/β-甘油磷酸钠(CS/β-GP)温敏水凝胶,并研究其凝胶形成的相转变机制和体外释药性能。方法以生物可降解壳聚糖为载体,以β-甘油磷酸钠为促凝剂制备载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶,采用动态透析法考察其体外释药性能,运用流变学方法研究凝胶形成的相转变机制。结果优化的制备载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶的工艺条件为:β-甘油磷酸钠质量浓度560 mg·m L-1、壳聚糖质量浓度22 mg·m L-1、酸溶剂为0.1 mol·L-1冰乙酸、壳聚糖/β-甘油磷酸钠体积比8.75∶1.25,在37℃下其凝胶化时间为338 s。壳聚糖/β-甘油磷酸钠水凝胶对高乌甲素具有缓释作用,其释药行为符合Higuchi模型和Korsmeyer-Peppas模型,为溶散释放。流变学研究表明,壳聚糖/β-甘油磷酸钠温敏水凝胶属于触变体系,具有类似非牛顿流体的剪切变稀的性质,表现出一种"类固体"的凝胶行为。结论成功制备了具有较好弹性及强度的载高乌甲素可注射壳聚糖/β-甘油磷酸钠温敏水凝胶,且其体外释药具有明显的缓释特征。OBJECTIVE To prepare lappaeonitine（ LA）-loaded chitosan/sodium β-glycerophosphate（CS/β-GP） thermosensitive hydrogels and investigate its phase transition mechanism of gel formation process and release properties in vitro. METHODS The in- jectable CS/β-GP thennosensitive hydrogels were prepared with biodegradable CS as carrier material and β-GP as eoagulation aecelera- tor. The release behavior in vitro was studied by dynamic dialysis, and the phase transition mechanism of gel formation process was fur- ther investigated by theological method. RESULTS The optimized process condition was as follows：the eoneentration of β-GP and CS was 560 and 22 mg· mL^-1 , respectively, CS was dissolved by 0. 1mol· L^-1 HOAc, and the valume ratio of CS to β-GP was 8.75： 1.25（V/V） , the gelation time of CS/β-GP thermosensitive hydrogels with volume ratio of 8.75：1.25 （V/V） at 37℃ was 5 rain 38 s. The il7 vitro release study showed that these injectable CS/β-GP thermosensitive hydrogels had sustained release effect for LA, and the release behavior eouht be well described by the Higuehi model and Korsmeyer-Peppas model. The mechanism of LA releasing from CS/β-GP thermosensitive hydrogels was attributed to drug dissolution and diffusion. Rheologieat studies showed that the CS/β-GP thermo- sensitive hydrngels beblonged to thixotropic system and exhibited non-Newtonian and shear-thinning fluid behavior as well as ＂solid-like＂ gelatin behavior. CONCLUSION LA-Loaded CS/β-GP injectable thermosensitive hydrogels with good elasticity and gel strength properties are prepared sueeessfully, and they show sustained release efleet of LA in vitro.

关 键 词：温敏水凝胶 壳聚糖 β-甘油磷酸钠 高乌甲素 

分 类 号：R944[医药卫生—药剂学]