靛玉红固体脂质纳米粒的制备及Caco-2单层细胞转运研究

Preparation of Indirubin Solid Lipid Nanoparticles and Transport of Caco-2 Monolayer Cells

目的制备靛玉红(indirubin,IND)固体脂质纳米粒(IND-SLN),并通过Caco-2单层细胞转运实验评价其渗透性。方法采用溶剂注入法制备IND-SLN,以包封率和粒径为考察指标,进行单因素筛选,用Box-Behnken响应面优化处方,采用透析法评价IND-SLN的体外释放,通过Caco-2单层细胞转运实验比较了IND原料药与IND-SLN的渗透性。结果经优化得到IND-SLN最优处方:药物与载体脂质比例1∶15;载体脂质与磷脂比例1∶1。透射电镜下IND-SLN呈球状分布,无聚集;IND-SLN粒径为(189.93±7.23)nm;Zeta电位为(-31.67±0.60)mV;差示扫描量热法(DSC)测定显示,IND-SLN中的药物吸热峰消失;体外释放实验中,IND-SLN累积释放度较原料药明显增加;Caco-2细胞实验测得IND-SLN表观渗透系数为(5.19±2.18)×10^(-10)cm^(2)·s^(-1),远高于原料药。结论将IND制备成IND-SLN可显著提高药物渗透性。

OBJECTIVE To prepare indirubin(IND)solid lipid nanoparticles(IND-SLN)and evaluate their permeability by Caco-2 monolayer cell transport experiments.METHODS IND-SLN was prepared by solvent injection method.The encapsulation efficiency and particle size were used as the indexes for single factor screening.The formulation was optimized by Box-Behnken response surface.The in vitro release of IND-SLN was evaluated by dialysis method.The permeability of IND drug substance and IND-SLN was compared by Caco-2 monolayer cell transport experiment.RESULTS The optimal prescription of IND-SLN was:the ratio of drug to carrier lipid was 1∶15.The ratio of carrier lipid to phospholipid was 1∶1.Under the transmission electron microscope,IND-SLN showed spherical distribution and no aggregation.The particle size of IND-SLN was(189.93±7.23)nm.Zeta potential was(-31.67±0.60)mV.DSC showed that the endothermic peak of the drug in IND-SLN disappeared.In the in vitro release experiment,the cumulative release of IND-SLN was significantly higher than that of API.The apparent permeability coefficient of IND-SLN measured by Caco-2 cell experiment was(5.19±2.18)×10^(-10) cm^(2)·s^(-1),which is much higher than that of API.CONCLUSION Preparation of IND into IND-SLN can significantly improve drug permeability.