摘要
目的制备牛血清白蛋白/壳聚糖双层包覆染料木素脂质体(genistein liposomes bilayer-coated by bovine serum albumin/chitosan,BSA/CS-Gen-Lip),并考察口服药动学行为。方法单因素考察结合Box-Behnken设计-响应面法筛选染料木素脂质体(genistein liposomes,Gen-Lip)最佳处方工艺,并进一步制备成BSA/CS-Gen-Lip。透射电子显微镜(transmission electron microscope,TEM)观察微观形貌,X射线粉末衍射法(X-ray powder diffraction method,XRPD)分析晶型,比较不同pH值释放介质中的释药情况。以染料木素原料药为参考,比较BSA/CS-Gen-Lip在体内药物代谢动力学行为。结果BSA/CS-GenLip最佳制备条件为磷脂与胆固醇比为10.1∶1,脂药比20.7∶1,水化时间为1.5 h,壳聚糖质量浓度为0.2%,BSA质量浓度为0.5%。BSA/CS-Gen-Lip包封率为(89.53±1.60)%,载药量为(1.87±1.41)%,粒径为(303.84±23.67)nm,ζ电位为(-13.27±0.89)m V。TEM显示BSA/CS-Gen-Lip无黏连现象,XRPD分析表明染料木素在BSA/CS-Gen-Lip冻干粉中以无定型状态存在。BSA/CS-Gen-Lip冻干粉在pH 2.0或p H 7.4磷酸盐缓冲液中体外释药过程均符合Weibull模型。药动学结果显示,BSA/CS-Gen-Lip的达峰时间(time to peak,t_(max))延后至(2.17±0.71)h,半衰期(half-life period,t_(1/2))延长至(6.89±1.12)h,达峰浓度(peak concentration,C_(max))和相对口服吸收生物利用度分别提高至2.33倍和4.00倍。结论BSA/CSGen-Lip显著改变了染料木素药动学行为,增加了口服吸收生物利用度。
Objective To prepare genistein liposomes bilayer-coated by bovine serum albumin/chitosan(BSA/CS-Gen-Lip),and study its oral pharmacokinetic behavior.Methods Single factor investigation method combined with Box-Behnken design-response surface method was used to investigate the optimal prescriptions of genistein liposomes(Gen-Lip),and then BSA/CS-Gen-Lip was prepared.The morphology of BSA/CS-Gen-Lip was observed by transmission electron microscopy(TEM),crystal forms were analyzed by X-ray powder diffraction method(XRPD).Drug release in different pH media was compared.Using genistein as a reference,pharmacokinetics behavior in vivo of BSA/CS-Gen-Lip was compared.Results The optimal prescriptions for BSA/CSGen-Lip:phospholipids to cholesterol ratio was 10.1∶1,lipids to drug ratio was 20.7∶1,hydration time was 1.5 h,chitosan concentration was 0.2%and BSA concentration was 0.5%.Encapsulation efficiency,drug loading,particle size andζpotential were(89.53±1.60)%,(1.87±1.41)%,(303.84±23.67)nm,(−13.27±0.89)mV,respectively.TEM showed no adhesion in BSA/CS-GenLip,and XRPD analysis showed that genistein existed as an amorphous state in BSA/CS-Gen-Lip lyophilized powder.In vitro release of BSA/CS-Gen-Lip lyophilized powder in pH 2.0 or pH 7.4 phosphate buffer(PBS)was in accordance with Weibull model.Pharmacokinetic result showed that time to peak(t_(max))of BSA/CS-Gen-Lip was delayed to(2.17±0.71)h,time to peak(t_(1/2))prolonged to(6.89±1.12)h,peak concentration(C_(max))and oral bioavailability increased to 2.33 times and 4.00 times.Conclusion BSA/CS-Gen-Lip significantly altered the pharmacokinetic behavior of genistein and increased its oral bioavailability effectively.
作者
刘万路
LIU Wan-lu(Weihai Ocean Vocational College,Weihai 264300,China)
出处
《中草药》
CAS
CSCD
北大核心
2023年第24期8018-8030,共13页
Chinese Traditional and Herbal Drugs
基金
国家自然科学青年基金资助项目(51804021)
山东省高等学校海洋食品药品资源开发新技术研发中心科研专项资金项目(SDSY20230011)。
