T. Musumeci, M. Serapide, R. Pellitteri
Nov 3, 2018
Citations
1
Influential Citations
49
Citations
Quality indicators
Journal
European Journal of Pharmaceutics and Biopharmaceutics
Abstract
&NA; The brain as a target for drug delivery is a challenge in pharmaceutical research. Among the several proposed strategies, the intranasal route represents a good strategy to deliver drugs to the brain. The goal of this study was to investigate the potential use of oxcarbazepine (OXC) to enhance brain targeting efficiency after intranasal (IN) administration. As well as attempting to use as low a dose as possible to obtain therapeutic effect. Our results showed that, after IN administrations, the dose of OXC that was effective in controlling epileptic seizures was 0.5 mg/kg (1 dose, every 20 min for 1 h) in rodents, confirmed by Cerebral Spinal Fluid (CSF) bioavailability. With the aim of reducing the number of administrations, sustaining drug release and increasing brain targeting, OXC was loaded into poly(lactide‐co‐glycolide) (PLGA) nanoparticles (NPs). The selected nanoformulation for in vivo studies was obtained re‐suspending the freeze‐dried and cryo‐protected OXC loaded PLGA NPs. The translocation of 1‐1′‐Dioctadecyl‐3,3,3′,3′‐tetramethylindotricarbocyanine Iodide loaded PLGA NPs, from nose to the brain, was confirmed by Fluorescence Molecular Tomography, which also evidenced an accumulation of NPs in the brain after repeated IN administrations. IN administrations of OXC loaded PLGA NPs reduced the number of administrations to 1 over 24 h compared to the free drug thus controlling seizures in rats. Immunohistochemical evaluations (anti‐neurofilament, anti‐beta tubulin, and anti‐caspase3) demonstrated a neuroprotective effect of OXC PLGA NPs after 16 days of treatment. These encouraging results confirmed the possibility of developing a novel non‐invasive nose to brain delivery system of OXC for the treatment of epilepsy. Graphical abstract Figure. No caption available. HighlightsPreparation and characterization of OXC loaded PLGA NPs for nose to brain delivery.FMT on rodents demonstrated translocation of fluorescent labelled NPs from nose to brain.OXC was detected in the CSF of rodents through HPLC analysis after IN administration.Nose to brain delivery and OXC PLGA NPs control epileptic seizures.Immunohistochemistry confirmed the advantage of intranasal administered nanomedicine.