Thermoresponsive Gel-loaded Oxcarbazepine Nanosystems for Nose- To-Brain Delivery: Enhanced Antiepileptic Activity in Rats

Background Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation...

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Bibliographic Details
Published in:Pharmaceutical research Vol. 40; no. 7; pp. 1835 - 1852
Main Authors: Abou-Taleb, Basant A., El-Ganainy, Samar O.
Format: Journal Article
Language:English
Published: New York Springer US 01-07-2023
Springer
Springer Nature B.V
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Summary:Background Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation in mucoadhesive nanoparticles offers even more advantages for the nasal route. Objective The study aimed to develop oxcarbazepine-loaded chitosan nanoparticles (OXC-NP) added to a mucoadhesive thermo-reversible gel for intranasal delivery and enhancement of antiepileptic activity. Methods The formulation was optimized based on entrapment efficiency, polydispersity index, particle size, zeta potential, and in vitro release analysis. The therapeutic efficacy of OXC-NP was assessed in an epileptic rat model and compared to intranasal OXC and oral OXC. Results The optimized OXC-NPs with chitosan exhibited particle size, zeta potential, and entrapment efficiency of 189 nm, + 31.4 mV ± 2.5 and 97.6% ± 0.14, respectively. The release of OXC was prolonged, reaching 47.1% after 6 h and 55% after 24 h. Enhanced antiepileptic activity of OXC-NP was manifested as decreased seizure score and prolonged survival. Halting of hippocampal TNF-α and IL-6 together with upregulated IL-10 could explain its anti-inflammatory mechanisms. Conclusions Intranasal OXC-NP-loaded in situ gel represents a promising formulation for enhanced antiepileptic potential achieved at low drug concentrations.
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ISSN:0724-8741
1573-904X
1573-904X
DOI:10.1007/s11095-023-03552-7