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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10d的累积释放度为80%左右。VBL凝胶高剂量组(5.6×10-3pg·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。
OBJECTIVE To investigate the drug release characteristics of vinblastine sulfate sensitive gels and evaluate its antiangiogenic activity. Methods VBL gel was prepared from monomethyl polyethylene glycol-co-glycolic acid (MPEG-PLGA). The drug loading and release of VBL gel were determined by high performance liquid chromatography (HPLC) (CAM) experiment to investigate the inhibitory effect of different doses of VBL gel on CAM blood vessels. Results As the concentration of MPEG-PLGA solution increased, the temperature of solution phase transition decreased. The 20% MPEG-PLGA solution gelled at 37 ℃. The VBL gel showed 10% to 30% of burst at 2h, with a decrease in the amount of burst as the concentration of MPEG-PLGA increased. After 2h, the release rate of gel slowed down. After 3 days, the release rate of gel showed an accelerating trend. The cumulative release of 10% and 20% hydrogels was about 80% at 10 days. VBL gel high dose group (5.6 × 10-3pg · -1 chicken embryo) and low dose group (2.8 × 10-3pg · -1 chicken embryo) could significantly inhibit the formation of small vessel of CAM (P <0.01) , Of which high-dose group also significantly inhibited the formation of large blood vessels (P <0.05). Low dose of VBL gel significantly inhibited the small blood vessels of CAM compared with the same dose of water solution (P <0.01). The high dose of VBL gel had the same effect on the large and small vessel of CAM as the same dose of aqueous solution P> 0.05). Conclusion VBL thermogelling gel has obvious sustained-release characteristics, which can obviously inhibit the angiogenesis of CAM through the continuous action of low dose.