目的 制备白屈菜红碱脂质体（chelerythrine liposomes，Che-Lip）和聚乙二醇修饰白屈菜红碱脂质体（PEGylated chelerythrine liposomes，PEG-Che-Lip），考察其体外释药和体内口服药动学行为。方法 薄膜超声法制备Che-Lip和PEG-Che-Lip。单因素考察结合Box-Behnken响应面法优化Che-Lip处方，引入二硬脂酰磷脂酰乙醇胺-聚乙二醇2000（DSPE-mPEG2000）制备PEG-Che-Lip。比较Che-Lip和PEG-Che-Lip在模拟胃肠液中溶解度、稳定性和体外释药情况。按20 mg/kg ig给药（以白屈菜红碱计），测定血药浓度，计算Che-Lip和PEG-Che-Lip主要药动学参数及其相对口服吸收生物利用度。结果 最优处方下制备的Che-Lip和PEG-Che-Lip外观为球形及类球形。Che-Li和PEG-Che-Lip包封率分别为（82.54±0.62）%和（91.13±1.04）%，载药量为（7.64±0.11）%和（7.55±0.18）%，平均粒径分别为（148.15±7.63）nm和（159.37±8.14）nm，ζ电位分别为（-34.2±1.1）mV和（-4.2±0.3）mV。PEG-Che-Lip在模拟胃肠液稳定性高于Che-Lip，Che-Lip和PEG-Che-Lip释药过程均符合Weibull模型。药动学结果显示，Che-Lip的达峰浓度（C_max）和相对口服吸收生物利用度分别增加至1.55倍和2.45倍，PEG-Che-Lip的C_max和相对口服吸收生物利用度分别增加至2.08倍和5.04倍。结论 Che-Li和PEG-Che-Lip可有效促进口服吸收，PEG-Che-Lip优势更明显。

Objective To prepare chelerythrine liposomes (Che-Lip) and PEGylated chelerythrine liposomes (PEG-Che-Lip), and to study drug release in vitro and oral pharmacokinetic behavior in vivo. Methods Film-ultrasonic method was used to prepare Che-Lip and PEG-Che-Lip. Single factor investigation method combined with Box-Behnken response surface design method was used to investigate the optimal prescriptions of Che-Lip. PEG-Che-Lip was prepared by introducing polyethylene glycol phosphatidylethanolamine 2000 (DSPE-MPEG 2000). Solubility, stability and in vitro drug release of Che-Lip and PEG-Che-Lip in simulate gastrointestinal fluid were compared. Blood samples were collected after gastric administration at a dose of 20 mg/kg (chelerythrine), and plasma concentration was determined. Main pharmacokinetic parameters and relative oral bioavailability of Che-Lip and PEG-Che-Lip were also calculated. Results Under the optimal formulation, the appearance of Che-Lip and PEG-Che-Lip were spherical or nearly spherical, entrapment efficiency respectively were (82.54 ± 0.62)% and (91.13 ± 1.04)%, drug loading were (7.64 ± 0.11)% and (7.55 ± 0.18)%, average particles size were (148.15 ± 7.63) nm and (159.37 ± 8.14) nm, and ζ potential were (-34.2 ± 1.1) mV and (-4.2 ± 0.3) mV. The stability of PEG-Che-Lip in simulated gastrointestinal fluid was higher than that of Che-Lip. The drug release process of Che-Lip and PEG-Che-Lip both conformed to Weibull model. Pharmacokinetic results showed that C_max and relative oral bioavailability of Che-Lip was enhanced to1.55 times and 2.45 times, and PEG-Che-Lip was enhanced to 2.08 times and 5.04 times, respectively. Conclusion Both Che-Lip and PEG-Che-Lip could promote oral absorption effectively, and the effect of PEG-Che-Lip was more obvious.

R283.6

河南省高等学校重点科研项目计划（23B310010）