木犀草素磷脂复合物白蛋白纳米粒的制备及口服药动学评价  

Luteolin phospholipids complex albumin nanoparticle:Preparation and oral pharmacokinetics evaluation

作　　者：田莉 李伟宏 张付利 TIAN Li;LI Weihong;ZHANG Fuli(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Henan Vocational College of Applied Technology,Zhengzhou 450042,China;Henan University,Kaifeng 475001,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]河南应用技术职业学院,河南郑州450042 [3]河南大学,河南开封475001

出　　处：《中草药》2024年第10期3280-3290,共11页Chinese Traditional and Herbal Drugs

基　　金：河南省高等学校重点科研项目计划(23B320013);妇科肿瘤科研创新团队(2021-TD-02);郑州澍青医学高等专科学校骨干教师(2022zygg07)。

摘　　要：目的制备木犀草素磷脂复合物牛血清白蛋白纳米粒(luteolin phospholipids complex bovine serum albumin nanoparticles,Lut-PC-BSA-NPs),考察口服药动学行为。方法乳化-高压均质法制备Lut-PC-BSA-NPs,采用Box-Behnken设计-效应面法筛选Lut-PC-BSA-NPs最优处方,测定包封率、载药量、粒径及ζ电位等。冷冻干燥法制备成冻干粉末,X射线粉末衍射(X-ray powder diffraction,XRPD)法分析Lut-PC-BSA-NPs晶型,测定溶解度,考察在模拟胃肠液中的释药行为。SD大鼠按40 mg/kg剂量(以木犀草素计)ig给予Lut-PC-BSA-NPs后采血,计算Lut-PC-BSA-NPs主要药动学参数及相对生物利用度。结果Lut-PC-BSA-NPs最佳处方为水相与有机相体积比为14.3∶1、白蛋白浓度为1.9%,均质压力为85 MPa。Lut-PC-BSA-NPs包封率为(81.24±1.07)%,载药量为(2.32±0.11)%,平均粒径为(153.64±7.28)nm,ζ电位为(−16.43±0.21)mV。木犀草素在Lut-PC-BSA-NPs冻干粉中存在状态为无定型,在不同介质中溶解度均得到显著增加,体外释药过程符合Weibull模型。口服药动学结果表明,Lut-PC-BSA-NPs半衰期(t1/2)增加至(5.03±0.97)h,血药浓度(Cmax)增加至(2220.85±757.54)ng/mL,口服相对生物利用度提高至3.98倍。结论Lut-PC-BSA-NPs显著增加了木犀草素溶解度及口服相对生物利用度。Objective To optimize prescriptions of luteolin phospholipids complex bovine serum albumin nanoparticles(Lut-PCBSA-NPs),and carry out its pharmacokinetic behavior in vivo.Methods Emulsification-high pressure homogenization method was employed to prepare Lut-PC-BSA-NPs.Box-Behnken design-response surface methodology(BBD-RSM)was used to investigate its optimal prescriptions.Entrapment efficiency,drug loading,particle size andζpotential were determined.Lyophilized powder of LutPC-BSA-NPs was prepared by freeze-drying method.Crystal of Lut-PC-BSA-NPs lyophilized powder was analyzed by X-ray powder diffraction(XRPD).Solubility and drug release behavior in gastrointestinal fluid were determined.SD rats were administered intragastrically at a dose of 40 mg/kg(luteolin)and blood samples were collected,main pharmacokinetic parameters and relative bioavailability of Lut-PC-BSA-NPs were also calculated.Results Optimal formulation of Lut-PC-BSA-NPs:Volume ratio of water phase to organic phase was 14.3:1,concentration of albumin was 1.9%,and the homogeneous pressure was 85 MPa.Envelopment efficiency,drug loading,particle size andζpotential were(81.24±1.07)%,(2.32±0.11)%,(153.64±7.28)nm and(−16.43±0.21)mV,respectively.Luteolin existed as an amorphous state in Lut-PC-BSA-NPs lyophilized powder.Solubility of luteolin was significantly increased in different media,and the release process in vitro conformed to the Weibull model.Results of oral pharmacokinetics showed that t1/2 of Lut-PC-BSA-NPs was increased to(5.03±0.97)h,Cmax was enhanced to(2220.85±757.54)μg/mL and oral relative bioavailability was increased to 3.98 times.Conclusion Lut-PC-BSA-NPs significantly increased solubility and oral relative bioavailability of luteolin.

关 键 词：木犀草素 磷脂复合物 白蛋白纳米粒 Box-Behnken设计-效应面法 Weibull模型 口服药动学 生物利用度 

分 类 号：R283.6[医药卫生—中药学]