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胆酸修饰的联苯双酯脂质体体外肝实质细胞摄取特性

Bifendate liposomes modified by bile and its role in enhancing hepatocytes uptake in vitro

  • 摘要: 用胆酸修饰联苯双酯脂质体,以期通过受体配体特异性的结合,增加药物在肝实质细胞的蓄积。本研究采用薄膜超声法制备联苯双酯脂质体(LP-DDB)和胆酸修饰联苯双酯脂质体(BP2B-LP-DDB),采用葡聚糖凝胶法测定包封率,比较LP-DDB和BP2B-LP-DDB的理化性质差异;分离培养肝实质细胞,研究孵化温度、给药剂量等对肝实质细胞体外摄取上述两种脂质体的影响。BP2B的修饰对脂质体的包封率、粒径、多分散指数和Zeta电位均无显著性影响。LP-DDB和BP2B-LP-DDB中药物平均包封率分别为(90.66±1.22)%和(86.89±1.61)%,平均粒径分别为(309.52±16.74)和(273.77±14.14)nm,Zeta电位分别为(24.98±2.03)和(22.21±7.03)mV。与LP-DDB相比,BP2B-LP-DDB与肝实质细胞的结合及摄取均显著增加,具有明显的主动转运特征。胆酸修饰的脂质体可作为肝实质细胞靶向的载体,可以通过受体介导的方式促进药物向肝实质细胞内的传递。

     

    Abstract: The aim of this study was to investigate the possibility of using bile-modified liposomes as a targeting carrier to increase the accumulation of bifendate (DDB) in hepatic cells.Both liposomes (LP) and liposomes modified by bile (BP2B-LP) containing DDB(BP2B-LP-DDB) were prepared by the method of film ultrasonic dispersion.The entrapment efficiency of LP-DDB and BP2B-LP-DDB was determined following the separation by Sephadex gel and their physicochemical properties were also studied.Hepatic cellular uptake of LP-DDB and BP2B-LP-DDB was evaluated in vitro,including incubation temperature,the dose and the addition of bile.It revealed that the entrapment efficiencies of LP-DDB and BP2B-LP-DDB were about (90.66±1.22)% and (86.89±1.61)%;the mean size (309.52±16.74) nm and (273.77±14.14) nm;the Zeta potential (24.98±2.03 ) mV and (22.21±7.03) mV,respectively.And it was shown that there was remarkable increase in cellular uptake of BP2B-LP-DDB when compared to that of LP-DDB.Hence,BP2B-LP could be a targeting carrier to facilitate the delivery of the encapsulated DDB into the hepatocytes,possibly via the mechanism of receptor mediation.

     

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