Influence of chitosan coating on magnetic nanoparticles in endothelial cells and acute tissue biodistribution

MARIELA A. AGOTEGARAY (CORRESPONDING AUTHOR); ADRIAN CAMPELO; ROBERTO D. ZYSLER; FERNANDA A. GUMILAR; CRISTINA BRAS; ALEJANDRA MINETTI; VIRGINIA L. MASSHEIMER; VERÓNICA L. LASSALLE

Journal of Biomaterials Sciece, Polymer Edition

Taylor & Francis

Lugar: Oxfordshire; Año: 2016

Chitosan coating on magnetic nanoparticles (MNPs) was studied on biological systems as a first step toward the application in the biomedical field as drug targeted nanosystems. Composition of MNPs consists of magnetite functionalized with oleic acid and coated with the biopolymer chitosan or glutaraldehyde-crosslinked chitosan. The influence of the biopolymeric coating has been evaluated by in vitro and in vivo assays on the effects of these MNPs on rat aortic endothelial cells (ECs) viability and on the random tissue distribution in mice. Results were correlated with the physicochemical properties of the nanoparticles.Nitric oxide (NO) production by ECs was determined, considering that endothelial NO represents one of the major markers of ECs function. Cell viability was studied by MTT assay. Different doses of the MNPs (1, 10 and 100 µg/mL) were assayed, revealing that MNPs coated with non-crosslinked chitosan for 6 and 24 hours did not affect neither NO production nor cell viability. However, a significant decrease on cell viability was observed after 36 hours treatment with the highest dose of this nanocarrier. It was also revealed that the presence and dose of glutaraldehyde in the MNPs structureimpact on the cytotoxicity. The study of the acute tissue distribution was performed acutely in mice after 24 hours of an intraperitoneal injection of the MNPs and sub acutely, after 28 days of weekly administration. Both formulations greatly avoided the initial clearance by the reticulo-endothelial system (RES) in liver. Biological properties found for N1 and N2 in the performed assays reveal that chitosan coating improves biocompatibility of MNPs turning these magnetic nanosystems as promising devices for targeted drug delivery.