학술논문
载木犀草素纳米胶束的制备及其大鼠体内药动学研究 / Preparation of Luteolin-loaded Nanomicelles and Their Pharmacokinetics in Rats
Document Type
Academic Journal
Author
Source
中国现代中药 / Modern Chinese Medicine. 25(10):2179-2185
Subject
Language
Chinese
ISSN
1673-4890
Abstract
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.
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.
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.