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目的制备托氟啶(TFu)固体脂质纳米粒(TFu-SLN),并对其进行理化性质评价和小鼠体内药动学研究。方法HPLC法测定体内外TFu的含量;用薄膜分散法制备TFu-SLN;透射电镜观察纳米粒形态;激光粒度分析仪测定其粒径、粒度分布和zeta电位;以TFu50%乙腈溶液为对照,采用动态膜透析法分别考察TFu-SLN在磷酸盐缓冲液(pH7.4)、人工胃液(pH1.2)、人工肠液(pH6.8)以及人工胃液2h后转入人工肠液中至48h的体外释药情况;以TFu水混悬液组为对照,考察小鼠口服TFu-SLN后药动学性质。结果所制备的TFu-SLN呈球形或类球形,平均粒径为(156.5±s0.5)nm,zeta电位为(-30±4)mV,平均包封率为(84±4)%,平均载药量为(2.1±0.9)%。体外释放结果表明将TFu制成固体脂质纳米粒可明显延缓药物释放的时间。小鼠口服TFu-SLN相对于口服TFu水混悬液的生物利用度为209%。结论薄膜分散法制备的TFu固体脂质纳米粒包封率较高,具有一定的缓释能力,生物利用度较高,对促进难溶性药物口服具有一定意义。
Objective To prepare TFu-solid liposome nanoparticles (TFu-SLN) and to evaluate their physical and chemical properties and pharmacokinetics in mice. Methods The content of TFu in vitro and in vivo was determined by HPLC method. TFu-SLN was prepared by thin film dispersion method. The morphology of nanoparticles was observed by transmission electron microscopy. The particle size, particle size distribution and zeta potential were measured by laser particle size analyzer. Dynamic membrane dialysis method were used to investigate the in vitro release of TFu-SLN into artificial intestinal juice (pH7.4), artificial gastric juice (pH1.2), artificial intestinal juice (pH6.8) and artificial gastric juice The pharmacokinetics of TFu-SLN was evaluated by the TFu aqueous suspension group. Results The TFu-SLN prepared was spherical or spheroidal with an average particle size of (156.5 ± 0.5) nm and a zeta potential of (-30 ± 4) mV with an average entrapment efficiency of (84 ± 4)% Drug loading was (2.1 ± 0.9)%. In vitro release results show that the solid lipid nanoparticles made of TFu can delay the drug release time. The bioavailability of mouse oral TFu-SLN relative to an aqueous suspension of TFu was 209%. Conclusion The TFu solid lipid nanoparticles prepared by the method of membrane dispersion have higher entrapment efficiency, sustained release ability and higher bioavailability, which is of certain significance for promoting oral administration of poorly soluble drugs.