白屈菜红碱2种脂质体的制备和口服生物利用度比较  

Preparation of two kinds of chelerythrine liposomes and oral bioavailability comparison

作　　者：张体鹏 决利利 ZHANG Ti-peng;JUE Li-li(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Zhengzhou University of Industrial Technology,Zhengzhou 451150,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]郑州工业应用技术学院,河南郑州451150

出　　处：《中草药》2023年第17期5568-5579,共12页Chinese Traditional and Herbal Drugs

基　　金：河南省高等学校重点科研项目计划(23B310010)。

摘　　要：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PEGChe-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(DSPEmPEG2000)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(Cmax)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Cmax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,andζpotential 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 Cmax 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.

关 键 词：白屈菜红碱 脂质体 薄膜超声法 Box-Behnken响应面法 模拟胃肠液 口服生物利用度 

分 类 号：R283.6[医药卫生—中药学]