Oxcarbazepine-loaded nanoemulsions in thermosensitive nasal gels for epilepsy: in-vitro and in-vivo evaluation in status epilepticus rat model.

To overcome the low aqueous solubility of oxcarbazepine (OXC), a BCS Class II drug, and to enhance brain exposure following intranasal administration, OXC was formulated into a self-nanoemulsifying drug delivery system (SNEDDS) incorporated within a thermosensitive nasal gel. The optimized SNEDDS (SNE.O2), comprising rose oil, Tween 80, and Transcutol® P, exhibited a droplet size of 10.38 nm, a zeta potential of -15.3 mV, and 97.24% drug content. SNE.O2 was dispersed into a hydrogel containing 16% Poloxamer 407, 1% Poloxamer 188, and 1.5% sodium carboxymethyl cellulose, yielding the optimum nanogel NG3.6. The nanogel had a gelation temperature of 30.9 °C, and viscosities of 600 and 720 cP at 25 and 31 °C, respectively. Ex-vivo buffalo mucosal permeation from NG3.6 showed a 1.67-fold enhancement compared to OXC control gel. in-vivo pharmacokinetics demonstrated 7.7 and 13.0-fold improvements for NG3.6 over the oral suspension, and 1.6-fold and 1.9 improvements over C3, for Cmax and AUC0-last, respectively. Brain-to-plasma ratios were 2.55 for NG3.6 compared to 1.67 and 0.26 for C3 and the oral suspension, respectively, demonstrating enhanced brain delivery. In status epilepticus rat model, NG3.6 significantly suppressed NF-κB, IL-1β and reduced the median Racine score when compared to Li/Pil group. However, NG3.6 did not show significant score compared to C3. Moreover, no overt short term histological abnormalities were observed. Ultimately, NG3.6 provides a promising brain delivery system with the potential to improve oxcarbazepine delivery to CNS. Further studies are needed to establish its therapeutic advantage and whether it can reduce dosage requirements and systemic side effects.