Cubosome-based thermosensitive gelling system for intranasal administration of lamotrigine with enhanced antiepileptic efficacy.

Lamotrigine (LTG) is a second-generation antiepileptic drug that belongs to Biopharmaceutics Classification System (BCS) class II. LTG has a low probability of crossing the BBB if administered orally. This study was designed to fabricate LTG cubosomal dispersion that is further loaded in a thermosensitive gel to increase nasal residence time and enhance drug absorption across the nasal mucosal membrane. LTG-loaded cubosomes exhibited an entrapment efficiency ranging from 24.83% to 60.13%, a particle size ranging from 116.2 to 197.6 nm, and a zeta potential ≤-25.5 mV. The selected LTG-loaded cubosomal formulation was loaded in a thermosensitive gel (cubogel) employing different concentrations of poloxamer 407. release study revealed sustained drug release from cubosomal and cubogel compared with free drug suspension. studies revealed enhanced antiepileptic efficacy of LTG cubogel and LTG cubosomes compared with free drug in rats with pilocarpine-induced epilepsy by stimulating the release of gamma-aminobutyric acid GABA), total antioxidant capacity (TAC), and serotonin and by inhibiting the release of Ca, dopamine, acetylcholine (Ach), C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP). LTG cubogel exhibited superior activity over LTG cubosomes. These findings reveal that the developed cubosomal thermosensitive gel can enhance the antiepileptic efficacy of LTG the intranasal route.