Stability of topotecan reversed lipid-based nanoparticles in artificial intestinal fluids / 国际药学研究杂志

ABSTRACT

Objective To establish an analytical method to investigate the protective effect of reversed lipid-based nanoparti-cle(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 concentra-tions of both forms of TPT by high performance liquid chromatography(HPLC). Release curve of RLBN-TPT in simulated intestinal flu-id(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 0.25-5μg/ml for both forms of TPT. Compared with free TPT,RLBN-TPT significantly improved the stability of TPT in SIF as the per-centage 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.