拓扑替康反相脂质纳米粒在人工肠液中的稳定性

Stability of topotecan reversed lipid-based nanoparticles in artificial intestinal fluids

目的建立测定方法,检测反相脂质纳米粒(RLBN)对人工肠液中拓扑替康的保护作用。方法二步冻干-复溶法制备拓扑替康反相脂质纳米粒(RLBN-TPT)油溶液。建立高效液相色谱法(HPLC)同时测定拓扑替康两种构型的含量。考察RLBN-TPT在模拟肠液中的释放曲线,研究拓扑替康的稳定性。结果用优化的HPLC条件测定拓扑替康的内酯与开环形式,二者分离度符合要求,线性范围为0.25~5μg/ml。与拓扑替康水溶液比较,RLBN-TPT中的拓扑替康在肠液中的稳定性明显增强,开环构型产生的速率明显减小(P<0.05)。结论 RLBN能明显增强拓扑替康在肠液中的稳定性,这为拓扑替康口服新剂型的研制提供了依据。

Objective To establish an analytical method to investigate the protective effect of reversed lipid-based nanoparticle（RLBN）for topotecan（TPT）in artificial intestinal fluid. Methods Reversed lipid-based nanoparticle of TPT（RLBN-TPT）was prepared by the two-step methods of lyophilization and dissolution. An analytical method was established to determine the concentrations of both forms of TPT by high performance liquid chromatography（HPLC）. Release curve of RLBN-TPT in simulated intestinal fluid（SIF）was investigated to study the stability of TPT in gastrointestinal（GI）fluid. Results Both lactone and carboxylate forms of TPT were well separated and determined precisely by the optimized HPLC method. The calibration curves were linear within the range of 0.25-5 μg/ml for both forms of TPT. Compared with free TPT,RLBN-TPT significantly improved the stability of TPT in SIF as the percentage of carboxylate form was remarkably lower than the free TPT（P〈0.05）. Conclusion RLBN can significantly protect the TPT from hydrolysis in GI,which may lay the foundation for the deuelopment of oral chemotherapeutic drug with higher bioavailability.