目的 制备木犀草素磷脂复合物介孔二氧化硅纳米粒（Lut-PC-MSNs），并进行药动学评价。方法 采用溶剂挥发法制备Lut-PC-MSNs。以包封率、载药量、粒径和Zeta电位为指标，选择MSNs粉末与Lut-PC用量比、木犀草素质量浓度和搅拌时间为主要影响因素，Box-Behnken设计-效应面法筛选Lut-PC-MSNs最优处方。进行Lut-PC-MSNs样品表征，考察Lut-PC-MSNs在模拟胃肠液中的释药行为。SD大鼠ig给予Lut-PC-MSNs（以木犀草素计40 mg/kg），测定血药浓度，计算主要药动学参数和相对生物利用度。结果Lut-PC-MSNs最佳处方工艺为：MSNs粉末与Lut-PC用量比为1.45∶1.0，木犀草素质量浓度为1.1 mg/mL，搅拌时间为8.25 h。Lut-PC-MSNs粉末分散于纯化水后即可形成外观均一的混悬液。木犀草素在Lut-PC-MSNs以无定形状态存在。Lut-PC-MSNs在模拟胃肠液中累积释放度明显增加，释药行为符合Weibull模型。Lut-PC-MSNs药动学行为发生很大变化，口服吸收生物利用度提高至5.24倍。结论Lut-PC-MSNs处方简单，贮存稳定性好，显著增加了木犀草素口服吸收生物利用度。

Objective To prepare luteolin phospholipids complex mesoporous silica nanoparticles (Lut-PC-MSNs), and evaluate bioavailability. Methods Solvent evaporation method was employed to prepare Lut-PC-MSNs. Entrapment efficiency, drug loading, particle size, and Zeta potential were selected as indexes, MSNs powder to Lut-PC dosage ratio, luteolin concentration, and stirring time were selected as main influencing factors, and Box-Behnken design-response surface methodology was used to screen the optimal prescription of Lut-PC-MSNs. Lut-PC-MSNs samples were characterized, and release behavior in simulate gastrointestinal fluid were also investigated. SD rats were ig administered with Lut-PC-MSNs (calculated by luteolin, 40 mg/kg), its main pharmacokinetic parameters and relative bioavailability were calculated.Results Optimal formulation of Lut-PC-MSNs: dosage ratio of MSNs powder to Lut-PC was 1.45∶1.0, luteolin concentration was 1.1 mg/mL, and stirring time was 8.25 h. Lut-PC-MSNs powder could be dispersed in purified water to form a homogeneous suspension with a uniform appearance. Luteolin existed as an amorphous state in Lut-PC-MSNs powder, cumulative release rate in simulate gastrointestinal fluid was obviously increased, and drug release behavior accorded with Weibull model. The pharmacokinetic behavior of Lut-PC-MSNs underwent significant changes, and oral bioavailability was increased to 5.24-fold. Conclusion Prescription of Lut-PC-MSNs is simple with its good storage stability, and can significantly increase the bioavailability of luteolin.

R943;R969.1

河南省高等学校重点科研项目计划（23B310010）