Carbamazepine loaded solid lipid nanoparticles for the treatment of refractory epilepsy

SCIOLI MONTOTO, SEBASTIÁN; ISLAN, GERMAN; RUIZ, MARÍA ESPERANZA; COUYOUPETROU, MANUEL; SBARAGLINI, MARIA LAURA; MURACA, GIULIANA; ALVAREZ, VERA ALEJANDRA; PESCE, GUIDO OSCAR; TALEVI, ALAN; CASTRO, GUILLERMO RAÚL

Mar del Plata

Congreso; Reunión Conjunta de SAIC, SAFE, SAB y SAP; 2019

SAIC - SAFE - SAB - SAP

Epilepsy is the most common neurological disorder affecting around 50 million people worldwide, most of them refractory to traditional antiepileptic drugs (AED) therapies. Due to the restrictions imposed by the blood brain barrier to the entrance of foreign substances into the central nervous system, generally, high doses of AED are needed in order to achieve a therapeutic effect. A hypothesis that would explain refractoriness is the overexpression at BBB level of efflux transporters such as P-gp that would decrease the AED bioavailability in brain. The aim of this work was to develop prolonged release CBZ-loaded solid lipid nanoparticles (SLN), with enhanced distribution and brain bioavailability. SLN 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) DLS, 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 after 2 hs of 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. Cells permeability studies showed significant favourable differences (p