title: Nimodipine-Loaded Pluronic®Block Copolymer Micelles: Preparation, Characterization,In-vitroandIn-vivoStudies.
abstract: Nimodipine (NM), as a lipophilic calcium channel blocker indicated for the prevention and treatment of neurological disorders, suffers from an extensive first pass metabolism, resulting in low oral bioavailability. Polymeric micelles, self-assembled from amphiphilic polymers, have a core-shell structure which makes them unique nano-carriers with excellent performance as drug delivery. This investigation was aimed to develop NM-loaded polymeric micelles and evaluate their potential to cross the blood brain barrier (BBB). Micelles from Pluronics®P85, F127 and F68 were fabricated for the delivery of NM, using thin film hydration and direct dissolution techniques. Critical micelle concentration of the drug-free micelles was determined by pyrene ﬂuorescence spectroscopy. Dynamic light scattering showed that in most cases, micelles less than 100 nm and low polydispersity indices were successfully developed. Transmission electron microscopy demonstrated spherical shape of micelles. The NM-loaded micelles were also characterized for particle size, morphology, entrapment efficiency, drug loading , in vitro drug release in phosphate buffer and artificial cerebrospinal fluid (CSF). Stability was assessed from size analysis, clarity of dispersion on standing and EE(%), following 3 months storage at room temperature. Thein-vitrorelease of NM from polymeric micelles presented the sustained-release profile. Animal studies revealed the existence of fluorescein 5-isothiocyanate-labeled micelles in rat CSF following intraperitoneal administration, proving that the micelles crossed the BBB. Anticonvulsant effect of NM was shown to be significantly greater than that of NM solution. Our results confirmed that Pluronic micelles might serve as a potential nanocarrier to improve the activity of NM in brain.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Sotoudegan
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Faizi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Aboofazeli
keywords: Blood brain barrier; FITC; Nimodipine; Pluronics; Polymeric micelles