壳聚糖包覆芒果苷脂质体的制备、表征及口服药动学评价  

Chitosan-coated mangifer in liposomes:preparation,characterization and oral pharmacokinetic evaluations

作　　者：王涛丽 李登云 张莉 张国明[2] 兰天 WANG Taoli;LI Dengyun;ZHANG Li;ZHANG Guoming;LAN Tian(Zhengzhou School of Medicine,University of Industrial Technology,Henan Zhengzhou 451150,China;Department of Pharmacy,Shanghai Institute of Traditional Chinese Medicine,Shanghai,201401,China;Technology Center,Henan Runhong Pharmaceutical Inc,Henan Zhengzhou 451110,China)

机构地区：[1]郑州工业应用技术学院医学院,河南郑州451150 [2]上海市中药研究所药学部,上海201401 [3]河南润弘制药股份有限公司技术中心,河南郑州451100

出　　处：《中国医院药学杂志》2024年第18期2122-2128,共7页Chinese Journal of Hospital Pharmacy

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t_(max)、t_(1/2)、MRT、C_(max)、AUC_(0-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。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 parameters.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 intragastrically 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%.Average 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 amorphous state in CS-MF-Lips lyophilized powder.Sustained release characteristics of CS-MF-Lips in vitro were obvious and solubility rose to 8.41 folds.t_(max),t_(1/2),MRT,C_(max),AUC_(0-t) and CL of CS-MF-Lips altered significantly when comparing with mangiferin (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.

关 键 词：芒果苷 壳聚糖 脂质体 生物利用度 

分 类 号：R945[医药卫生—微生物与生化药学]