载紫杉醇的聚乙二醇-聚乳酸-聚-β-氨基酯纳米胶束药动学及其在小鼠体内分布研究

发布时间：2018-05-19 08:49

本文选题：紫杉醇 + 聚乙二醇-聚乳酸-聚-β-氨基酯　；参考：《中国新药杂志》2016年08期

【摘要】：目的:建立测定小鼠血液及各组织样品中紫杉醇含量测定的HPLC方法,考察比较包载紫杉醇(paclitaxel,PTX)的聚乙二醇-聚乳酸-聚-β-氨基酯(PELA-PBAE)与聚乙二醇-聚乳酸(PELA)纳米胶束在正常小鼠体内各组织的分布情况及药动学参数。方法:采用尾静脉注射法给予小鼠紫杉醇注射液(PTX injection)、PELA/PTX纳米胶束和PELA-PBAE/PTX纳米胶束,给药量为5 mg·kg~(-1)(以紫杉醇计),比较其药动学参数。结果:与紫杉醇注射液相比,2种纳米胶束在小鼠体内的AUC增大,平均滞留时间延长,在血、肺中蓄积量增多,在心脏蓄积减少;与非p H敏感性紫杉醇纳米胶束PELA/PTX相比,PELA-PBAE/PTX各药动学参数没有显著变化。结论:聚-β-氨基酯的引入没有改变原有胶束的优异性能,同样可以降低网状内皮系统对胶束的吞噬,可提高紫杉醇的生物利用度、延长药物的作用时间并降低紫杉醇的潜在心脏毒性。
[Abstract]:Objective: to establish a HPLC method for the determination of paclitaxel in blood and tissues of mice. The distribution and pharmacokinetic parameters of PELA-PBAE and PELA-PELA-PELA-loaded paclitaxellae containing paclitaxellae (PTX) micelles in normal mice were investigated. Methods: mice were injected with paclitaxel injection (PEL / PTX / PTX nanoparticles and PELA-PBAE/PTX nanoparticles) by tail vein injection at a dose of 5 mg / kg ~ (-1) (calculated by paclitaxel) and the pharmacokinetic parameters were compared. Results: compared with paclitaxel injection, the AUC of the two kinds of micelles in mice was increased, the mean retention time was prolonged, the accumulation in blood and lung was increased, and the accumulation in heart was decreased. Compared with non-pH-sensitive paclitaxel nano-micelle PELA/PTX, the pharmacokinetic parameters of PELA-PBAE / PTX were not significantly changed. Conclusion: the introduction of poly (尾 -aminoester) can not change the excellent properties of the original micelles, but also reduce the phagocytosis of the micelles in the reticular endothelial system and increase the bioavailability of paclitaxel. Prolongs the duration of the drug and reduces the potential cardiac toxicity of paclitaxel.
【作者单位】：中国中医药科学院中药研究所;北京中医药大学中药学院;
【基金】：国家“重大新药创制”科技重大专项(2014ZX09304307001) 北京市自然科学基金(2152036)
【分类号】：R965

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