PAMAM DENDRIMERS AS AN EFFICIENT CARBAMAZEPINE DELIVERY SYSTEM: NANOTOXICOLOGICAL CHARACTERIZATION

MARTINEZ CS; IGARTUA DE; PRIETO MJ; ALONSO SDV

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Carbamazepine (CBZ) is on the market as an antiepileptic. It alsohas potential uses for the treatment of numerous neurodegenerativediseases. However, it has low solubility in aqueous media, inefficientpharmacokinetic profiles and multiple side effects, so it is importantto avoid widespread distribution. Drugs delivery systems (DDS)have gained relevance in the field of nano- and bio-medicines. PAMAM dendrimers G4.0 and G4.5 are optimal polymers as DDSthat would increase the solubility of CBZ and the arrival to the brain.Our objective was to characterize complexes between CBZ anddendrimers and to study their nanotoxicity. In vitro toxicity in humanred blood cells was analyzed by hemolysis and in cell culture bycolorimetric methods (MTT, crystal violet and neutral red). In vivotoxicity was studied in zebrafish animal model.No hemolytic activity or morphological changes for any of the formulationswere observed. As regards in vitro toxicity, different effectswere observed for free drug, dendrimers and complexes, whichallowed us to predict toxicity mechanism. In vivo toxicity showed nomarked toxic effects between free drug and the complexes.It has been developed a DDS based on dendrimers capable ofefficiently transport the antiepileptic drug CBZ; what´s more, it is nottoxic in in vitro and in vivo models.