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-PLGA 溶液在 37 ℃ 左右胶凝。 VBL 凝胶在 2 h 表现出 10%~30% 的突释，随着 MPEG-PLGA 的浓度的增加，突释量减小。 2 h 以后凝胶的释药速度减慢，第 3 天以后释药速度又呈现出加快的趋势， 10% 和 20% 的水凝胶在 10 d 的累积释放度为 80% 左右。 VBL 凝胶高剂量组（ 5.6×10-3 pg · 个 -1 鸡胚）和低剂量组（ 2.8×10-3pg · 个 -1 鸡胚）均能明显抑制 CAM 小血管的生成 (<>P<0.01) ，其中高剂量组还能够明显抑制大血管的生成 (<>P<0.05) 。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 (<>P<0.01) ，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（ <> P >0.05 ）。 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。
Abstract
OBJECTIVE 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 with chicken chorioallantoic membrane (CAM) neovascularisation model. RESULTS Gelation temperature was decreased with the increased MPEG-PLGA concentration. 20% MPEG-PLGA solution became a gel state at physiological temperature (37 ℃).VBL hydrogels emerged 10%~30% burst release at 2 h, initial burst release was decreased with the increased MPEG-PLGA concentration. Drug release rate became slower during 2~3 d and became faster after 3 d. About 80% of VBL was released at day 10 from hydrogels at 10% and 20% MPEG-PLGA concentration. VBL hydrogels significantly inhibited small vessels forming at the dose of 2.8×10-3pg·egg-1 and 5.6×10-3pg·egg-1, markedly inhibited the big vessels angiogenesis at the dose of 5.6×10-3pg·egg-1. Anti-angiogenic effect on small vessels of VBL hydrogels at the dose of 2.8×10-3pg·egg-1 was greater than VBL solution at the same dose. VBL hydrogels and solution at the dose of 5.6×10-3pg·egg-1 had similar anti-angiogenic effects on small and big vessels. CONCLUSION VBL hydrogels exerted a remarkable controlled release characteristic and could significantly reduce CAM neovascularisation by continue action at lower dose.
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
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Key words
vinblastine sulfate /
MPEG-PLGA /
thermosensitive hydrogels /
chick chorioallantoic membrane /
angiogenic Inhibitor
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参考文献
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（ 收稿日期 ： 2008-11-20 ）
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