长循环紫杉醇微乳用于肿瘤小剂量化疗的研究
Paclitaxel carried by long circulating microemulsions used for metronomic chemotherapy of cancer
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摘要:
以聚乙二醇-二硬脂酰基磷脂酰乙醇胺 (PEG-DSPE) 为表面活性剂, 以维生素E为油相, 研制长循环紫杉醇微乳 (paclitaxel carried by long circulating microemulsions, TXL-M), 并评价其抗肿瘤作用。采用电子显微镜、激光粒度/zeta电位分析仪,观察了TXL-M的形态, 测定了TXL-M的粒度分布和zeta电位。用昆明种小鼠评价了TXL-M的毒性。采用小剂量化疗方案和动物肿瘤模型, 评价了TXL-M的抗肿瘤作用。通过测定给药后不同时间的血浆药物浓度和肿瘤中的药物含量, 评价了TXL-M的长循环效果及其在肿瘤中的分布。结果表明, TXL-M呈圆球形, 粒径为 (98.6 ± 11.2) nm, zeta电位为 (−32.4 ± 6.8) mV。采用小剂量给药方案, 静脉注射后, 与紫杉醇相比长循环微乳显著延长了紫杉醇的血液循环时间, 显著提高了紫杉醇的抗肿瘤作用, 同时显著减轻了紫杉醇的毒性。总之, TXL-M比紫杉醇更适用于肿瘤的小剂量化疗, 有可能成为一种较好的抗肿瘤药物。
Abstract:Long circulating paclitaxel microemulsions (TXL-M) were prepared and its anticancer effect was evaluated in metronomic chemotherapy of cancer using animal tumor models. In TXL-M, paclitaxel was dissolved in vitamin E and polylene glycol derivative of distearoylphosphatidyl ethanolamine (PEG-DSPE) was used as surfactant. The shape and particle size distribution of TXL-M were evaluated using an electronic microscope and a laser size scanner. The toxicity comparisons of TXL-M and paclitaxel were conducted using mice. Its anticancer effect and long circulation were evaluated using animal tumor model in C57BL/6 mice. The average diameter of TXL-M was (98.6 ± 11.2) nm and its zeta potential was (−32.4 ± 6.8) mV. Compared with paclitaxel, TXL-M showed lower toxicity. When used in metronomic chemotherapy of cancer, TXL-M showed longer circulation time in the blood and greater anticancer effect than paclitaxel. Thus, TXL-M is a better candidate for metronomic chemotherapy of cancer than paclitaxel injection.
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