Caracterização química e atividade biológica da rifampicina adsorvida à nanopartículas magnéticas de óxido de ferro

Abstract

Rifampicin, despite being an established antibiotic in the treatment of leprosy, tuberculosis and Staphylococcus aureus infections, this drug can cause serious adverse events such as nephrotoxicity and hepatotoxicity in prolonged therapy or administration of high doses. The nanoparticles arise as release promising platforms of drugs, contributing to the decrease of side and toxic effects. This study aimed to associate rifampicin with nanoparticles of iron oxide, perform chemical characterization and evaluate toxicological and antimicrobial activity. Nanoparticles of iron oxide were synthesized by coprecipitation method, coated with lauric acid and then absorbed to rifampicin. Such system was characterized by Ultravioletvisible spectroscopy, Fourier transform spectroscopy infrared, X-ray diffractometry and dynamic light scattering. The toxicity of the compound was determined by Artemia salina lethality assay and, posteriorly, its antimicrobial activity was evaluated by disk diffusion antimicrobial susceptibility testing. The results demonstrated that 55% of the rifampicin was adsorbed to the fluid according to the UV-vis technique. The infrared region of the spectra showed the presence of lauric acid combined with nanoparticles and also confirmed the presence of the rifampicin to the system. The average diameter of the magnetite and maghemite particles were estimated by X-ray diffraction, which revealed 8 nm dimensions in both cases. The antimicrobial activity of rifampicin was decreased when absorbed in the fluid, regarding free rifampicin, against Staphylococcus aureus strain. And disks impregnated with only nanoparticles showed no inhibition zone. The free rifampicin showed a moderate toxicity (LC50 312.94), while rifampicin absorbed in the fluid showed low toxicity (LC50 535.38) to the de Artemia salina nauplii. And it was found that iron oxide nanoparticles were non-toxic even at high concentration of 3000 μg.mL-1. Furthermore, it was observed behaviors of swimming speed increase and accumulation of nanoparticles in the intestine of Artemia salina, however, these alterations did not induce mortality of crustaceans. The absence of toxicity increases the prospect of the compound applications as possible drug carrier.