Estudo da biodistribuição e biocompatibilidade de nanopartículas magnéticas à base de maguemita recobertas com DMSA em macacos-prego (Cebus spp.) juvenis mediante análise morfológica

AUTOR(ES)

Victoria Monge-Fuentes

DATA DE PUBLICAÇÃO

2009

RESUMO

It is essential to determine the biodistribution and biocompatibility of magnetic nanoparticles (MNPs) for in vivo biomedical applications in order to ensure their safe clinical use. Biodistribution of MNPs depends on their properties, such as surface characteristics, size, shape and charge, which can all affect biodistribution, clearance, particle-cell interactions, and interactions with serum protein. Equally important is determining iron clearance as MNPs degrade, due to the fact that excessive free iron tissue accumulation is known to cause toxicity. Therefore, maghemite based magnetic nanoparticles coated with meso 2,3-dimercaptosuccinic acid DMSA were injected in non-human primates (Cebus apella), sacrificed 12 hours, 30 and 90 days after intravenous administration of MNPs. MNPs were distributed in all study organs, being more abundant in the lungs, liver, kidney, and spleen, in all experimental times, showing that as time advanced, less agglomerates were observed in the tissue. Brain, cerebellum, pancreas, heart, and intestines showed very few MNPs agglomerates; therefore, their use for therapeutic applications was not considered. Main DMSA-MNP elimination route was observed to be done by the liver, followed by the kidney, not discarding elimination through the air ways as a parallel route. Morphological alterations were only seen in the liver obtained 90 days after DMSA-MF administration, showing a dilated Disse space. This hepatotoxicity could be due to iron overload. Possible light immunosuppression induced by iron overload is also considered. In conclusion, to our knowledge this work represents the first histological, hematological, biochemical, and clinical study which used magnetic nanoparticles in a non-human primate experimental model, bringing nanomaterial use for therapeutical purposes in human beings a step closer.

ASSUNTO(S)

nanotoxicity magnetic fluid nanopartícula magnética biodistribuição óxido de ferro ácido meso 2,3-dimercaptosuccínico magnetic nanoparticle biodistribution biocompatibilidade nanotoxicidade fluido magnético primatas não-humanos ciencias da saude iron oxide biocompatibility meso 2,3-dimercaptosuccinic acid non-human primates

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