Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy

Objective: The aim of the present work was to investigate the efficacy of nanostructured lipid carriers (NLCs) to enhance the brain targeting of lamotrigine (LMT) following intranasal (IN) administration. Methods: Formulation was optimized using four-factor three levels Box-Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation. The developed formulation was subjected to stability study, in vivo efficacy and scintigraphic study in Wistar rat model. Results: The NLCs had a mean particle size of 151.6 +/- 7.6 nm, polydispersity index of 0.249 +/- 0.035, zeta potential of 11.75 +/- 2.96 mV and EE of 96.64 +/- 4.27%. The drug release from NLCs followed Fickian diffusion with a flux value of 11.73 mu gcm(-2)h(-1). Sustained drug concentration was obtained in NLCs carrying LMT after IN administration after 24 h. gamma scintigraphy studies further proved high accumulation of drug in brain. Conclusion: Hence we can conclude that IN administration of LMT NLCs in rats is able to maintain higher brain concentration of LMT compared to IN and oral drug solution.