载木犀草素纳米胶束的制备及其大鼠体内药动学研究

目的:制备木犀草素纳米胶束(LUT-NMs),以提高药物的口服生物利用度。方法:以聚氧乙烯聚氧丙烯醚嵌段共聚物Pluronic F127和Pluronic P123作为纳米胶束载体材料,使用溶剂蒸发-薄膜水化分散法将木犀草素制备成聚合物胶束;以LUT-NMs处方中的聚合物与药物质量比、Pluronic F127与Pluronic P123质量比作为考察因素,以包封率、粒径分布和多聚分散系数(PDI)作为评价指标,采用二因素三水平中心复合响应面法优化了LUT-NMs的处方;通过透射电镜、稀释稳定性和体外药物释放对LUT-NMs的理化性质进行了评价;考察了大鼠口服LUT-NMs的相对生物利用度。结果:实验设计获得LUT-NMs的最佳处方为聚合物与药物质量比为45∶1,Pluronic F127与Pluronic P123质量比为5∶1;在透射电镜下可观察到LUT-NMs呈圆整球形,LUT-NMs的稀释稳定性良好,在不同pH介质溶液中释药速率缓慢且释药速率之间无差异;大鼠体内药动学结果显示,LUT-NMs可显著提高药物的达峰浓度,增加药物口服生物利用度。结论:将木犀草素制备成纳米胶束,可显著提高药物的口服生物利用度。

Preparation of Luteolin-loaded Nanomicelles and Their Pharmacokinetics in Rats

Objective To prepare luteolin-loaded nanomicelles (LUT-NMs) to improve the oral bioavailability of LUT.Methods The poly (ethylene oxide)-poly (propylene oxide) block copolymers Pluronic F127 and Pluronic P123 were used as micellar carrier materials to prepare LUT-NMs by solvent evaporation-film hydration dispersion method. The formulation of LUT-NMs was optimized by two-factor three-level central composite design, with the mass ratio of polymer:drug (X₁) and the mass ratio of Pluronic F127 and Pluronic P123 (X₂) as independent variables and the encapsulation efficiency (Y₁), particle size distribution (Y₂) and polydispersity index (Y₃) of LUT-NMs as the dependent variable. The physicochemical properties of LUT-NMs were investigated by transmission electron microscopy, dilution stability and in vitro drug release. The relative bioavailability of orally administered LUT-NMs in rats was investigated.Results The optimal formulation of LUT-NMs obtained by experimental design was as follows: the mass ratio of polymer to drug was 45:1, and the mass ratio of Pluronic F127 to Pluronic P123 was 5:1. Transmission electron microscopy revealed that LUT-NMs had a spherical shape. LUT-NMs exhibited excellent dilution stability, and the drug release rate was slow in solutions of different pH values, with no difference between them. The pharmacokinetic results showed that LUT-NMs could significantly increase the peak concentration and increase the oral bioavailability of LUT in rats.Conclusion Preparation of LUT into NMs can significantly improve the oral bioavailability of LUT.