Lamotrigine loaded nano-liposomes enhance brain selectivity in vivo

For many patients with refractory epilepsy, antiepileptic drugs (AEDs) cannot reach effective therapeutic concentration in brain due to drugtolerance. In order to increase the selectivity of lamotrigine in brain, lamotrigine loaded nano-liposomes (LTG-NL) were designed, prepared, and the physio-chemical characterizations were observed. The distribution of LTG-NL in mice was studied by detecting the concentration of LTG extracted from animal organs, then targeting efficiency (TE) and targeting index (TI) were calculated to evaluate the brain targeting effect of LTG-NL. The mechanism of LTG-NL entry into cell was determined by A549 cell internalization experiments. The results showed that LTG-NL were small and uniform spherical particles with high entrapment efficiency and release. In vivo distribution study showed brain selectivity of LTG-NL, and TE and TI values further demonstrated the targeting capacity of LTG-NL. The cell internalization of LTG-NL was mainly by the pathway of clathrin-mediated endocytosis and macropinocytosis. These findings suggested this lipid formulation would be a drug delivery system for insoluble drugs to promote drug release and enhance brain selectivity.