硫酸长春碱温敏性凝胶的释药特性和抗血管生成活性研究.doc

硫酸长春碱温敏性凝胶的释药特性和抗血管生成活性研究 符旭东，胡江红，鲁有祥，张孟佑（广州军区武汉总医院药剂科，武汉，430070） 摘要 目的 考察硫酸长春碱（VBL）温敏性凝胶的释药特征，并评价其抗血管生成活性。方法 以单甲基聚乙二醇－羟基乙酸共聚物（MPEG-PLGA）为材料制备VBL凝胶，运用高效液相色谱法测定VBL凝胶的载药量和释放度，采用鸡胚尿囊膜（CAM）实验考察不同剂量的VBL凝胶对CAM血管的抑制作用。结果 随着MPEG-PLGA溶液浓度的增加，溶液发生相转变的温度降低，20％MPEG-PLG溶液在37℃左右胶凝。VBL凝胶在2h表现出10％～30％的突释，随着MPEG-PLGA的浓度的增加，突释量减小。2h以后凝胶的释药速度减慢，第3d以后释药速度又呈现出加快的趋势，10％和20％的水凝胶在10d的累积释放度为80％左右。VBL凝胶高剂量组（5.6×10-3pg/个鸡胚）和低剂量组（2.8×10-3pg/个鸡胚）均能明显抑制CAM小血管的生成(P0.01)，其中高剂量组还能够明显抑制大血管的生成(P0.05)。低剂量的VBL凝胶剂对CAM小血管的抑制作用明显优于相同剂量的水溶液(P0.01)，高剂量的VBL凝胶剂对CAM大、小血管的抑制作用与相同剂量的水溶液相当（P0.05）。结论 VBL温敏性凝胶具有明显的缓释特征，通过低剂量持续作用的方式可以明显地抑制CAM血管生成。 关键词： 硫酸长春碱; 单甲基聚乙二醇－羟基乙酸共聚物; 温敏性凝胶；鸡胚尿囊膜；血管生成抑制剂 Studies on drug release characteristic and anti-angiogenic activity of Vinblastine sulfate thermosensitive hydrogels Xu-dong Fu, Jianghong Hu ，You-xiang Lu, , Meng-you Zhang（Wuhan General Hospital of Guanzhou Command, Wuhan 430030） ABSTRACT To examine drug release profile of vinblastine sulfate (VBL) thermosensitive hydrogels and evaluate its anti-angiogenic activity. METHODS Vinblastine sulfate hydrogels were prepared with MPEG-PLGA. HPLC was used to determine drug content and in vitro release rate. The anti-angiogenic effect in vivo was evaluated on chicken chorioallantoic membrane (CAM) neovascularisation model. RESULTS Gelation temperature was decreased with the concentration of MPEG-PLGA improved. 20% MPEG-PLGA solution became a gel state at physiological temperature (37℃).VBL hydrogels emerged 10%~30% burst release at 2h, initial burst release was decreased with the concentration of MPEG-PLGA improved. Drug release rate became slower during 2h~3d and became faster after 3d .About 80% of VBL was released at day 10 from hydrogels at MPEG-PLGA concentration of 10% and 20％. VBL hydrogels significantly inhibit small vessls forming at the dose of 2.8×10-3pg/egg and 5.6×10-3pg/egg, markedly inhibited the big vessels angiogenesis at the dose of 5.6×10-3pg/egg. Anti-angiogenic effect on small vessels of VBL hydrogels at the d