LIPID NANOPARTICLES FOR THE TREATMENT OF REFRACTORY EPILEPSY: PK/PD EVALUATION.

RUIZ MA; SBARAGLINI ML; PESCE GO; SCIOLI MONTOTO S; DI IANNI M; MURACA, GIULIANA; TALEVI A; ISLAN GA; COUYOUPETROU M; ALVAREZ, VERA A.; CASTRO GR

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Las Sociedades Argentinas de Investigación Clínica (SAIC), de Farmacología Experimental (SAFE), de Biología (SAB), de Protozoología (SAP), de Nanomedicinas (NANOMEDar) la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)

Epilepsy is the most common neurological disorder affecting around 50 million people worldwide, most of them refractory to traditional antiepileptic drugs (AED) therapy. Due to the restrictions imposed by the blood brain barrier (BBB) to the entrance of foreign substances into the central nervous system (CNS), generally, high doses of AED are needed in order to achieve a therapeutic effect. A hypothesis that would explain refractoriness is the overexpression at the BBB of efflux transporters such as P-gp, that would decrease the CNS bioavailability of the AEDs. Our goal was to develop lipid nanoparticles (LN) loaded with the AED Carbamazepine (CBZ), with enhanced distribution and brain bioavailability. LN were synthesized using the emulsification by ultrasonication technique. All formulation prepared were characterized in terms of their entrapment efficiency (% EE), particle size (PS), polydispersity index (PDI), Z-potential (Z-pot), thermal and structural properties, stability, in vitro release kinetic, permeability through cells monolayer and anticonvulsant activity. Finally, the amount of CBZ in brain was quantified at different times after administration. All formulation showed high % EE (89 - 96 %) and spherical shape, with an average PS of 163 nm, a low PDI and z-pot (between -2.4 and -6.3 mV). Sustained release was obtained during the time of the assay. Thermal and structural tests proved that CBZ was molecularly dispersed within the lipid matrix. Some of the LP formulations showed an enhance permeability (p