目的 本实验以聚丙交酯-乙交酯-聚乙二醇-聚丙交酯-乙交酯(PLGA-PEG-PLGA)和盐酸小檗碱(berberine, BBR)制备瘤内给药的BBR温敏凝胶,探讨瘤内注射后与紫杉醇注射液联用对4T1荷瘤鼠的药理作用。方法 以PLGA-PEG-PLGA为凝胶基质和BBR制备BBR温敏凝胶。选取相转变温度为考察因素优化处方,采用无膜溶出法结合UV考察其体外释放结果。建立4T1荷瘤Balb/c小鼠模型,对BBR温敏凝胶的瘤内给药并联用紫杉醇静脉注射的抗肿瘤效果做出评价。结果 成功制备BBR温敏凝胶,载药量为3 mg·mL-1质量浓度的温敏凝胶相转变温度(36.5±0.3)℃,符合瘤内注射的需求;体外释放结果表明该凝胶具有缓释作用,可持续释放至少14 d。药效实验结果显示,BBR温敏凝胶联合紫杉醇注射液对荷瘤鼠的抑瘤效果比单用紫杉醇注射液效果好(P＜0.05)。结论 本实验成功制备了一种温敏凝胶,通过瘤内注射与紫杉醇注射液联用可以增强紫杉醇对4T1荷瘤鼠的肿瘤抑制作用,具有良好的应用前景。
Abstract
OBJECTIVE To prepare berberine hydrochloride thermosensitive gelfor intratumoral injection by PLGA-PEG-PLGA and berberine, and investigate the pharmacological effects of combination with paclitaxel injectionafter intratumoral injection on 4T1 tumor bearing mice. METHODS Berberine hydrochloride thermosensitive gel was prepared with PLGA-PEG-PLGA as gel matrix and berberine hydrochloride. Phase transition temperature was selected as the investigation factor to optimize the prescription, and the release results in vitro were investigated by membrane-free dissolution combined with UV method. The 4T1 tumor-bearing Balb/c mouse model was established to evaluate the anti-tumor effect of berberine hydrochloride thermosensitive gel in vivo. RESULTS Berberine hydrochloride thermosensitive gel was successfully prepared. The drug loading was 3 mg·mL-1 and the phase transition temperature of thermosensitive gel was (36.5±0.3)℃, which met the needs of intratumoral injection. The results of in vitro release show that the gel has sustained release effect and can be released for at least 14 days. The results of pharmacodynamic experiments showed that berberine hydrochloride thermosensitive gel combined with paclitaxel injection had better antitumor effect than paclitaxel injection alone (P<0.05). CONCLUSION A thermosensitive gel is successfully prepared in this experiment. The combination of intratumoral injection and paclitaxel injection can enhance the tumor inhibitory effect of paclitaxel on 4T1 tumor-bearing mice, which has a good application prospect.
关键词
盐酸小檗碱 /
温敏凝胶 /
紫杉醇 /
乳腺癌 /
联合治疗
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Key words
berberine hydrochloride /
thermosensitive gel /
paclitaxel /
breast cancer /
combined therapy
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中图分类号：
R944
R965
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参考文献
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脚注
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基金
国家自然科学基金项目资助(81403117);浙江省基础公益研究计划资助(LGF20H280010)
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