目的 制備木犀草素磷脂復合物介孔二氧化硅納米粒（Lut-PC-MSNs），并進行藥動學評價。方法 采用溶劑揮發(fā)法制備Lut-PC-MSNs。以包封率、載藥量、粒徑和Zeta電位為指標，選擇MSNs粉末與Lut-PC用量比、木犀草素質(zhì)量濃度和攪拌時間為主要影響因素，Box-Behnken設計-效應面法篩選Lut-PC-MSNs最優(yōu)處方。進行Lut-PC-MSNs樣品表征，考察Lut-PC-MSNs在模擬胃腸液中的釋藥行為。SD大鼠ig給予Lut-PC-MSNs（以木犀草素計40 mg/kg），測定血藥濃度，計算主要藥動學參數(shù)和相對生物利用度。結(jié)果Lut-PC-MSNs最佳處方工藝為：MSNs粉末與Lut-PC用量比為1.45∶1.0，木犀草素質(zhì)量濃度為1.1 mg/mL，攪拌時間為8.25 h。Lut-PC-MSNs粉末分散于純化水后即可形成外觀均一的混懸液。木犀草素在Lut-PC-MSNs以無定形狀態(tài)存在。Lut-PC-MSNs在模擬胃腸液中累積釋放度明顯增加，釋藥行為符合Weibull模型。Lut-PC-MSNs藥動學行為發(fā)生很大變化，口服吸收生物利用度提高至5.24倍。結(jié)論Lut-PC-MSNs處方簡單，貯存穩(wěn)定性好，顯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

河南省高等學校重點科研項目計劃（23B310010）