SOLID SILICA-FUNCTIONALIZED MAGNETIC NANOPARTICLES AS DRUG

AGOTEGARAY MARIELA; CAMPELO ADRIÁN; MASSHEIMER VIRGINIA; LASALLE VERÓNICA

Mar del Plata

Congreso; LXI Reunión Científica anual de la Sociedad Argentina de investigación Clínica.; 2016

https://drive.google.com/open?id=0B_Ts6lxE2MlNVHhzdDUtaU4zRmc

Introduction: Solid silica (Si) coated magnetic nanoparticles (MNPs) are potential devices for drug targeting. Stability and bio-compatibility of silica turn these systems feasible forbiomedical ap-plications althoughdrug loading is a challenge due to silica inertia. Objective: Synthesis, characterization and Diclofenac (Dic) incor-poration onto citric acid(CA)-functionalized magnetite(MG) coated with Siand 3-aminopropyltriethoxysilane(APTES). Evaluation of cy-totoxicity on rat aortic endothelial cells (EC). Design: MG/CA NPs were obtained by co-precipitation. Si and APTES functionalization was performed bya modified Stöber process, prolonged for 12h at room temperature, using ratios MG/CA:TEOS:APTES=(1:0.5:2; 1:1:2; 1:2:2), named 1, 2, and 3. They were characterized by FTIR, DLS, z potential and HR-TEM microscopy. Dic was bonded by N,N´-dicyclohexylcarbodiimideand studied by UV-Vis spectroscopy. Primary cultures of EC were exposed for 48h to final concentrations of 1, 10 and 100µg/mL of MNPs and Dic-loaded MNPs. Cell viability was studied by MTT assay and by the capacity to produce NO (DAN assay). Results: 1 and 2 presented Dh of 400.0±10.0nm and 520±10.0nm; z of 27.9±5.78mV and21.9±6.02mV in aqueous dispersions. 3 was polydisperse with z 32.6±5.81mV. HR-TEM micrographs showed matrix dispersed structures for the MNPs. Formulation 2 incorporated approx. 40% of Dic. Cell viability was not affected at 10µg/mL or below for all the samples (p<0.001). Basal NO production was not altered at any of the assayed con-centrations for allMNPs except for Dic loaded nanocarrier at 100µg/mL (p<0.001). Conclusion: Synthesis of Si/APTES functionalized MNPs rendered aqueous dispersible formulations dependant on  precursors´ ratio and concentrations. Diclofenac was covalently incorporated. EC cytotoxicity was dose and drug dependent. No adverse effects for unloaded MNPs were observed. These novel nanocarriers may be suitable for drug targeting.