卡维地洛纳米结构脂质载体的制备与大鼠肠道吸收研究

Study on preparation and intestinal absorption characteristics of carvedilol nanostructured lipid carrier in rats

目的制备卡维地洛纳米结构脂质载体(CAR-loaded-NLCs),并通过大鼠原位灌注模型考察CAR-loaded-NLCs在大鼠肠道的吸收特征。方法用高压均质法制备CAR-loaded-NLCs,通过单因素实验考察处方组成对CAR-loaded-NLCs制剂性质的影响,测定CAR-loaded-NLCs的粒径分布、多聚分散系数(polydispersity index,PDI)和Zeta电位,在透射电镜下观察CAR-loaded-NLCs的微观形貌,考察CAR-loaded-NLCs在pH1.2、pH4.5、pH6.8介质溶液中的药物释放速率;通过大鼠原位灌注实验考察CAR-loaded-NLCs在大鼠肠道的吸动力学特征。结果选择双硬脂酸甘油酯(precirol ATO 5)作为固体脂质、肉豆蔻酸异丙酯作为液体脂质、D-α-维生素E聚乙二醇琥珀酸酯作为表面活性剂制备CAR-loaded-NLCs,平均粒径为(91.4±3.6)nm,PDI为(0.167±0.004),Zeta电位为(-28.7±0.7)mV,呈规则球状分布,大小均匀;CAR-loaded-NLCs在3种pH溶液中表现为双相释药特征;CAR-loaded-NLCs在大鼠肠道的吸收速率明显高于CAR混悬液。结论将CAR制备成纳米结构脂质载体,能够促进肠道对药物的吸收,有望提高CAR的口服生物利用度。

Objective To prepare carvedilol loaded nanostructured lipid carriers(CAR-loaded-NLCs),and by using in situ perfusion model to investigate the absorption characteristics of CAR-loaded-NLCs in rat intestines.Methods The CAR-loaded-NLCs were prepared by high-pressure homogenization method.Through single factor experiments,the influence of formulation composition on the properties of CAR-loaded-NLCs was investigated.The particle size distribution,polydispersity index(PDI)and Zeta potential of CAR-loaded-NLCs were measured by a Malvern laser particle size analyzer.The microscopic morphology of CARloaded-NLCs was observed under transmission electron microscope.The drug release rate of CAR-loaded-NLCs in pH1.2,pH4.5 and pH 6.8 solution was investigated.In situ perfusion experiments in rats were used to investigate the kinetic characteristics of CAR-loaded-NLCs in rat intestines.Results Precirol ATO 5 was selected as the solid lipid,isopropyl myristate as the liquid lipid,and D-α-tocopherol polyethylene glycol 1000 succinate as the surfactant.The prepared CAR-loaded-NLCs had an average particle size of(91.4±3.6)nm,PDI of(0.167±0.004),and Zeta potential of(-28.7±0.7)mV,with regular spherical distribution and uniform size.The CAR-loaded-NLCs exhibits biphasic drug release characteristics in different pH medium solution.The absorption rate of CAR-loaded-NLCs in the whole intestine of rats was significantly higher than that of the CAR suspensions.Conclusion The CAR-loaded-NLCs can enhance the drug absorption and be expected to improve the oral bioavailability of CAR.