OX26/ApoE共修饰的载小檗碱介孔二氧化硅纳米粒药动学研究

Pharmacokinetic study of OX26/ApoE co-modified berberine-loaded mesoporous silica nanoparticles

[目的]制备羧基功能化介孔二氧化硅纳米载体颗粒(MSNs-COOH),通过表面偶联转铁蛋白受体单克隆抗体(OX26)和载脂蛋白E(ApoE),增加包载小檗碱(BBR)的介孔二氧化硅纳米颗粒透过血脑屏障并靶向于脑部能力。[方法]采用模板剂法制备MSNs-COOH,碳二亚胺法偶联OX26和ApoE,浸渍法将BBR包载于孔道内。通过透射电子显微镜(TEM)、激光粒度分析仪、氮气吸脱附法等对载体进行表征,透析袋法考察制剂在体外释放特性,尾静脉注射给药后测定大鼠血浆及脑组织中药物浓度,计算药动学参数,评价制剂脑部靶向性。[结果]制备的MSNs-COOH在透射电镜下为有序孔道的球形颗粒,平均粒径为(129.8±1.3)nm,载药量为(10.71-20.39)%,体外释放结果显示该载体具有缓释特性,药动学参数表明制剂组的AUC与BBR溶液组有显著性差别,脑靶向指数大于1。[结论]所构建的OX26/ApoE共修饰的小檗碱介孔二氧化硅纳米载体能改善药物口服吸收差的缺点,实现药物的脑部靶向治疗,具有一定的脑靶向性。

[Objective]To prepare mesoporous silica nanoparticles functionalized with carboxyl groups(MSNs-COOH),and couple transferrin receptor monoclonal antibody(OX26)and apolipoprotein E(ApoE)through surface to make the mesoporous silica carrier loaded with berberine(BBR-MSNs)penetrate the blood-brain barrier(BBB)and increase the ability of targeting to the brain.[Methods]MSNs-COOH was prepared by the template method,OX26 and ApoE were coupled by the carbodiimide method,and the BBR was successfully encapsulated in the channel by the dipping method.A series of characterization of the carrier were carried out by transmission electron microscope(TEM),laser particle size analyzer,N2 absorption and desorption method,etc.To investigate the vitro release of BBR through dialysis bag method.Tail vein injection to determine the drug concentration in rat plasma and brain tissue,and pharmacokinetic parameters were fitted to evaluate the drug’s brain targeting.[Results]The MSNs-COOH was spherical particles with ordered pores under TEM.The average particle size was(129.83±1.27)nm,and the drug loading was(10.71~20.39)%.The vitro release showed obvious slow and controlled release characteristics.Pharmacokinetic parameters showed that the AUC of OX26/ApoE co-modified BBR-loaded MSNs(BBR-MSNs-OX26/ApoE)was significantly different from the BBR solution group,and the brain targeting index was greater than one.[Conclusion]The constructed BBR brain-targeted MSNs can improve the shortcomings of poor oral absorption of drugs,and achieve brain-targeted therapy of drugs with certain brain targeting.