中草药2026，Vol.57Issue(12)：4594-4608,15.DOI:10.7501/j.issn.0253-2670.2026.12.008
脱氧胆酸和壳聚糖双修饰的牡荆素脂质体制备及口服动力学研究
Preparation and oral pharmacokinetics study of vitexin liposomes co-modified with deoxycholic acid and chitosan
摘要
Abstract
Objective Vitexin liposomes(Vit-Lips),chitosan modified Vit-Lips(CS-Vit-Lips)and deoxycholic acid and chitosan co-modified Vit-Lips(DA/CS-Vit-Lips)were prepared,and their oral pharmacokinetic behavior were compared.Methods Deoxycholic acid-chitosan complex(DA/CS)was synthesized.Film-ultrasonic method was used to prepare Vit-Lips.Encapsulation rate,drug loading and particle size were used as evaluation indexes,single factor investigation combined with Box-Behnken design-response surface methodology(BBD-RSM)were used to investigate the optimal prescriptions of Vit-Lips.CS-Vit-Lips and DA/CS-Vit-Lips were prepared by introducing chitosan and DA/CS,respectively.Transmission electron microscopy(TEM)was used to observe the microstructure of the three kinds of liposomes,and their particle stability in gastrointestinal fluids were compared.Using vitexin as reference,the drug release of Vit-Lips,CS-Vit-Lips and DA/CS-Vit-Lips in simulate gastrointestinal fluid were compared,and their drug release mechanism were also studied.The absorption of the vitexin and its three kinds of liposomes in different intestinal segments was investigated,and the intestinal absorption parameters were calculated.Blood samples were collected after gastric administration of vitexin and its three kinds of liposomes at a dose of 20 mg/kg(vitexin),respectively.Main pharmacokinetic parameters and relative oral bioavailability were also calculated.Results The optimal formulation of Vit-Lips:phospholipids to cholesterol dose ratio was 7.95:1,lipids to drug dose ratio was 9.63:1 and hydration time was 30.00 min.CS-Vit-Lips and DA/CS-Vit-Lips were prepared using chitosan and DA/CS solution with mass fraction of 0.8％,respectively.Entrapment efficiency of Vit-Lips,CS-Vit-Lips and DA/CS-Vit-Lips were(82.31±0.96)％,(84.93±1.17)％,(85.15±1.38)％,drug loading were(7.33±0.09)％,(6.24±0.08)％,(6.30±0.11)％,particles size were(197.70±5.07),(233.06±7.19),(237.93±6.96)nm,and ζ potential were(-28.81±0.86),(27.75±1.10),(26.14±1.13)mV,respectively.The appearance of three kinds of liposomes was spherical vesicular,particle stability of CS-Vit-Lips and DA/CS-Vit-Lips was higher than that of Vit-Lips in simulated gastrointestinal fluid.Vit-Lips,CS-Vit-Lips and DA/CS-Vit-Lips enhanced cumulative release rate to 91.02％,86.74％and 83.15％,respectively.The drug release process of the three kinds of liposomes conformed to Weibull model.The three kinds of liposomes effectively improved the absorption rate constant(Ka)and apparent absorption coefficient(Papp)of vitexin.Compared to vitexin,Vit-Lips,CS-Vit-Lips and DA/CS-Vit-Lips increased relative oral bioavailability to 1.10-fold,3.08-fold and 4.70-fold,respectively.The half-life time(t1/2)of CS-Vit-Lips and DA/CS-Vit-Lips had significantly prolonged(P＜0.01)and the peak concentration(Cmax)was significantly increased(P＜0.01).Conclusion CS-Vit-Lips and DA/CS-Vit-Lips effectively promoted the oral absorption of vitexin,and the advantage of DA/CS-Vit-Lips were more obvious,laying an experimental foundation for further research.关键词
牡荆素/脂质体/薄膜超声法/Box-Behnken设计-响应面法/壳聚糖/脱氧胆酸/修饰/在体单向肠灌流/药动学行为Key words
vitexin/liposomes/film-ultrasonic method/Box-Behnken design-response surface methodology/chitosan/deoxycholic acid/modify/in situ single-pass intestinal perfusion/pharmacokinetic behavior分类
医药卫生引用本文复制引用
宋亚琼,李晓,穆卫卫,季少平..脱氧胆酸和壳聚糖双修饰的牡荆素脂质体制备及口服动力学研究[J].中草药,2026,57(12):4594-4608,15.基金项目
国家自然科学基金项目(31371386) （31371386）
国家自然科学基金项目(30871239) （30871239）
