RESUMO
The biodistribution profile of a new dextrin nanomagnetogel, which consists of γ-Fe2O3 superparamagnetic nanoparticles loaded within a polymeric matrix of modified dextrin, was studied in mice. The nanomagnetogel bear a monomodal size distribution profile (average diameter 110 nm) close to neutral surface charge and higher relaxivity (r2 = 215-248 mM(-1) s(-1) and r2/r1 = 13-11) than those of commercial formulations (r2 = 160-177 mM(-1) s(-1) and r2/r1 = 4-7). Also, the observed blood half-life-approximately 4 h-is superior to that of similar commercially available formulations, which remain for a few minutes in circulation. PEGylation resulted in 1.7- and 1.2-fold lower accumulation in the liver and spleen, respectively, within the first 24 h. Noteworthy, a good correlation was obtained between the amount of polymer (quantified by scintigraphy) in the spleen, 48 h after administration, and the amount of iron physically loaded through hydrophobic interactions (quantified by ICP) indicating the absence of iron leakage from the polymeric matrix. This study provides evidence of the in vivo stability of a self-assembled nanomagnetogel, a relevant feature which is seldom reported in the literature.
Assuntos
Dextrinas/farmacocinética , Portadores de Fármacos , Compostos Férricos/farmacocinética , Nanopartículas de Magnetita/química , Animais , Dextrinas/química , Estabilidade de Medicamentos , Compostos Férricos/química , Géis , Meia-Vida , Interações Hidrofóbicas e Hidrofílicas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Polietilenoglicóis/química , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/ultraestrutura , Eletricidade Estática , Propriedades de Superfície , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
This study aims at the production and characterization of a "nanomagnetogel" consisting of superparamagnetic iron oxide nanoparticles (γ-Fe2O3) stabilized within a hydrophobized-dextrin nanogel. The nanomagnetogel obtained was extensively characterized with respect to physico-chemical (transmission electron microscopy, cryo-scanning electron microscopy, dynamic light scattering, small angle X-ray scattering), magnetic (relaxometry, MIAplex) and biocompatibility (interaction with cells) properties. The obtained nanomagnetogel formulation, with about 4 mM of iron and a diameter of 100 nm, presents relevant features as a promising magnetic resonance imaging (MRI) contrast agent, noteworthy superparamagnetic behavior, high stability, narrow size distribution and potential for magnetic guidance to target areas by means of an external magnetic field. High values of transverse relaxivity make the nanomagnetogel a promising T2 contrast agent, allowing enhanced lesion detectability through magnetic resonance imaging. The nanomagnetogel demonstrated non-toxicity for 3T3 fibroblast cultures and was efficiently internalized by bone marrow-derived macrophages, therefore having potential as a contrast agent for MRI of the organs associated with the reticuloendothelial system (spleen, liver). The production of the nanomagnetogel is simple and easy to scale up, thus offering great technological potential.
RESUMO
The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a gamma-emitting (153)Sm(3+) radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.