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（t_1/2）增加至（5.03±0.97）h，血药浓度（C_max）增加至（2 220.85±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-PC-BSA-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 and ζ potential were determined. Lyophilized powder of Lut-PC-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 and ζ potential 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 t_1/2 of Lut-PC-BSA-NPs was increased to (5.03 ± 0.97) h, C_max was enhanced to (2 220.85 ± 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.

R283.6

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）