以牛血清白蛋白为稳定剂制备紫檀茋聚乳酸-羟基乙酸共聚物纳米粒及口服药动学研究  

Preparation of pterostilbene PLGA nanoparticles with bovine serum albumin as stabilizer and oral pharmacokinetics study

作　　者：张春燕 李燕红[1] 陈乾 蒋会哲[3] ZHANG Chun-yan;LI Yan-hong;CHEN Qian;JIANG Hui-zhe(Huanghe Science and Technology College,Zhengzhou 450063,China;Henan University of Traditional Chinese medicine,Zhengzhou 450001,China;Zhengzhou Railway Vocational and Technical College,Zhengzhou 450052,China)

机构地区：[1]黄河科技学院,河南郑州450063 [2]河南中医药大学,河南郑州450001 [3]郑州铁路职业技术学院,河南郑州450052

出　　处：《中草药》2023年第14期4481-4492,共12页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(82104833)。

摘　　要：目的 优化牛血清白蛋白修饰紫檀茋聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒(bovine serum albumin-modified pterostilbene PLGA nanoparticles,BSA-Pte-PLGA-NPs)处方,进行体外及体内评价。方法 纳米沉淀法制备BSA-Pte-PLGA-NPs,以包封率、载药量和粒径大小为评价指标,单因素结合Box-Behnken效应面设计法筛选BSAPte-PLGA-NPs最优处方。采用乳糖作为冻干保护剂将BSA-Pte-PLGA-NPs制备成冻干粉,并进行表征。SD大鼠分为紫檀茋原料药组、物理混合物组和BSA-Pte-PLGA-NPs组,按40 mg/kg(以紫檀茋计)剂量ig给药,测定血药浓度,计算主要药动学参数及相对生物利用度。结果 BSA-Pte-PLGA-NPs最佳处方为BSA质量浓度为19.0 mg/mL、载药比为8.8∶1、水相与有机相体积比为8∶1。BSA-Pte-PLGA-NPs包封率为(86.69±1.81)%,载药量为(9.02±0.37)%,粒径为(176.10±8.12)nm。紫檀茋在BSA-Pte-PLGA-NPs冻干粉中以无定型形式存在。BSA-Pte-PLGA-NPs在pH 1.2或pH 7.4磷酸盐缓冲液中体外释药过程均与Weibull模型拟合度最高。药动学结果显示,BSA-Pte-PLGA-NPs达峰时间(tmax)延后至(2.11±0.60)h,半衰期(t1/2)延长至(4.82±0.89)h,相对口服吸收生物利用度提高至3.24倍。结论 BSA-Pte-PLGA-NPs可显著促进紫檀茋口服吸收,值得进一步研究。Objective To optimize the formulation of bovine serum albumin-modified pterostilbene PLGA nanoparticles(BSA-PtePLGA-NPs),and carry out in vitro and in vivo evaluation.Methods Nanoprecipitation method was used to prepare BSA-Pte-PLGANPs.Envelopment efficiency,drug loading and particle size were used as evaluation index,single factor investigation method combined with Box-Behnken response surface design method was employed to investigate the optimal prescriptions of BSA-Pte-PLGA-NPs.BSA-Pte-PLGA-NPs were prepared into lyophilized powder using lactose as freeze-dried protector,and the optimal formulation was characterized.SD rats were divided into pterostilbene suspension group,physical mixture group and BSA-Pte-PLGA-NPs group,blood samples were collected after gastric administration at a dose of 40 mg/kg(pterostilbene).The plasma concentrations were determined,main pharmacokinetic parameters and relative bioavailability were also calculated.Results Optimal formulation of BSA-Pte-PLGANPs:BSA mass concentration was 19.0 mg/mL,carriers to drug ratio was 8.8:1,and volume ratio of water phase to organic phase was 8:1.Envelopment efficiency,drug loading and particle size of BSA-Pte-PLGA-NPs were(86.69 ± 1.81)%,(9.02 ± 0.37)% and(176.10 ± 8.12) nm,respectively.Pterostilbene was existed as an amorphous form in lyophilized powder of BSA-Pte-PLGA-NPs.In vitro release of BSA-Pte-PLGA-NPs showed best conformed to Weibull model in pH 1.2 and pH 7.4 phosphate buffers.Pharmacokinetic results showed that tmax of BSA-Pte-PLGA-NPs was delayed to(2.11 ± 0.60) h,t1/2 was prolonged to(4.82 ± 0.89) h and relative oral bioavailability was enhanced to 3.24 times.Conclusion BSA-Pte-PLGA-NPs can significantly promote the oral absorption of pterostilbene,which was worthy of further study.

关 键 词：紫檀茋 牛血清白蛋白 PLGA纳米粒 纳米沉淀法 Box-Behnken设计-效应面法 Weibull模型 药动学 生物利用度 

分 类 号：R283.6[医药卫生—中药学]