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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Published in: | Pharmaceutical research Vol. 40; no. 7; pp. 1835 - 1852 |
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Main Authors: | , |
Format: | Journal Article |
Language: | English |
Published: |
New York
Springer US
01-07-2023
Springer Springer Nature B.V |
Subjects: | |
Online Access: | Get full text |
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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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0724-8741 1573-904X 1573-904X |
DOI: | 10.1007/s11095-023-03552-7 |