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BSA-Pte-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（t_max）延后至（2.11±0.60）h，半衰期（t_1/2）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-Pte-PLGA-NPs), and carry out in vitro and in vivo evaluation. Methods Nanoprecipitation method was used to prepare BSA-Pte-PLGA-NPs. 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-PLGA-NPs: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 t_max of BSA-Pte-PLGA-NPs was delayed to (2.11 ±0.60) h, t_1/2 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.

R283.6

国家自然科学基金项目（82104833）