摘要
目的:制备壳聚糖包覆芒果苷脂质体(CS-MF-Lips),考察其体外释药及药动学行为.方法:以包封率、载药量和粒径为指标,采用薄膜分散法制备,Box-Behnken响应面法筛选CS-MF-Lips处方工艺,制备CS-MF-Lips,冻干,并进行表征.灌胃给予芒果苷和CS-MF-Lips,测定血药浓度.结果:CS-MF-Lips最佳制备工艺为脂药比15.9∶1,磷脂与胆固醇比9.9∶1,壳聚糖质量分数为 0.18％.CS-MF-Lips 包封率为(85.92±1.48)％,载药量为(4.04±0.16)％,粒径为(196.74±10.37)nm,Zeta电位为(14.13±0.49)mV.CS-MF-Lips微观形貌呈椭圆形,芒果苷在CS-MF-Lips冻干粉中以无定形状态存在.体外释药结果表明CS-MF-Lips具有缓释特性,与原料药相比,CS-MF-Lips中药物溶解度提高8.41倍.与芒果苷原料药相比,CS-MF-Lips的tmax、t1/2、MRT、Cmax、AUC0-t及CL存在显著性差异(P＜0.05或P＜0.01),相对生物利用度为420.48％.结论:CS-MF-Lips可促进芒果苷口服吸收,为药效学评价奠定基础.
Abstract
OBJECTIVE To prepare chitosan-coated mangiferin liposomes(CS-MF-Lips)and explore its drug release in vitro and pharmacokinetic behaviors.METHODS Entrapment efficiency,drug loading and particle size were selected as param-eters.Box-Behnken response surface design method was employed for examining the optimal prescriptions of CS-MF-Lips.Lyophilized powder of CS-MF-Lips was prepared and then characterized.Sprague-Dawley(SD)rats were administered intragas-trically of mangiferin and CS-MF-Lips and plasma concentration was determined.RESULTS Optimal prescriptions for CS-MF-Lips:ratio of lipid-to-drug was 15.9∶1,ratio of phospholipid-to-cholesterol 9.9∶1 and concentration of chitosan 0.18％.Aver-age entrapment efficiency of CS-MF-Lips was(85.92±1.48)％,drug loading(4.04±0.16)％,particle size(196.74±10.37)nm and Zeta potential(14.13±0.49)mV.Micro-morphology of CS-MF-Lips was elliptical and mangiferin existed as an amor-phous state in CS-MF-Lips lyophilized powder.Sustained release characteristics of CS-MF-Lips in vitro were obvious and solu-bility rose to 8.41 folds.tmax,t1/2,MRT,Cmax,AUC0-t and CL of CS-MF-Lips altered significantly when comparing with mangif-erin(P＜0.05 or P＜0.01).Oral bioavailability spiked to 420.48％.CONCLUSION CS-MF-Lips may effectively promote oral absorption.It offers rationales for pharmacodynamic evaluations.
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