One-step self-assembled nanomicelles for improving the oral bioavailability of nimodipine
作者单位：Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University
会议名称：《2018年第十二届中国药物制剂大会》
会议日期：2018年
学科分类：1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床]
关 键 词：Nanomicelles Self-assembly Nimodipine Oral bioavailability Transport mechanism
摘 要：Our study aimed to develop a self-assembled nanomicelle for oral administration of nimodipine(NIM) with poor water solubility. The NIM-loaded self-assembled nanomicelles were prepared according to the one-step self-assembled technique. Briefly, NIM and Solutol HS15 were added in the flask by gently stirring at 60°C for 30 minutes. Using Solutol HS15, the NIM loaded self-assembled nanomicelles displayed a near spherical morphology with a narrow size distribution of 12.57 ± 0.21 nm(PDI = 0.071 ± 0.011). Compared with Nimotop(NIM tablets), the intestinal absorption of NIM from NIM nanomicelle in rats was improved by 3.13-and 2.25-fold in duodenum and jejunum at 1 h after oral administration. The cellular transport of NIM nanomicelle in Caco-2 cell monolayers was significantly enhanced compared to Nimotop?. Regarding the transport pathways, clathrin, lipid raft/caveolae and macropinocytosis mediated the cell uptake of NIM nanomicelles, while P-glycoprotein and endoplasmic reticulum/Golgi complex(ER/Golgi) pathways were involved in the exocytosis. Pharmacokinetic study showed that the AUC of NIM nanomicelles was 3.72-fold that of Nimotop? via oral administration in rats. Moreover, the NIM concentration in brain from NIM nanomicelle was dramatically improved. Therefore, Solutol HS15 based self-assembled nanomicelles represent a promising delivery system to enhance the oral bioavailability of NIM.