title: One-step self-assembled nanomicelles for improving the oral bioavailability of nimodipine.
abstract: Our study aimed to develop a self-assembled nanomicelle for oral administration of nimodipine (NIM) with poor water solubility. 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 (polydispersity index =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 hour after oral administration. The cellular transport of NIM nanomicelle in Caco-2 cell monolayers was significantly enhanced compared to that of 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 exocytosis. Pharmacokinetic studies in our research laboratory have showed that the area under the plasma concentration-time curve (AUC0-∞) of NIM nanomicelles was 3.72-fold that of Nimotop(®) via oral administration in rats. Moreover, the NIM concentration in the brain from NIM nanomicelles was dramatically improved. Therefore, Solutol(®) HS15-based self-assembled nanomicelles represent a promising delivery system to enhance the oral bioavailability of NIM.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Luo
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008823:Micelles; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D009553:Nimodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D008823:Micelles; D009553:Nimodipine
keywords: nanomicelles; nimodipine; oral bioavailability; stability; transport mecha nism