Avaliação da biocompatibilidade de magnetolipossomas à base de nanopartículas de maghemita

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Nanobiotechnology represents an emerging and promising research field. Nanostructured materials, such as magnetic fluids and magnetoliposomes (MLs), have been proposed for drug-delivery systems and thermal-based cancer therapy amongst other several applications in biomedicine. In particular, MLs are physiologically stable structures, consisting of magnetic nanoparticles (MNPs) wrapped by a phospholipid bilayer. A ML sample containing citrate-coated maghemite nanoparticles encapsulated in liposomes (called ML-Magh) was synthesized for biomedical applications purposes. Polyethylene glycol (PEG) was grafted onto the liposome bilayer. The aim of this work was to investigate the biological behaviour of ML-Magh (1,0 × 10 14 particle/ mL), by evaluating their biocompatibility/ toxicity through in vitro and in vivo tests. The particle size and surface charge potential of MLs were determined. They presented a mean particle size of 124 nm and a negative surface charge, as determined by measuring the zeta potential (-24,4 mV). To perform the in vitro test, human submandibular duct cells (HSG) and mesangial cells (CM) were cultivated during 24 hours in the presence of the ML-Magh sample at two different doses (50 L and 100 L). Analysis by light microscopy showed that ML-Magh does not induce morphological alterations on both cellular types. For the in vivo tests, 100 L of the ML-Magh sample were endovenously or intraperitoneally administrated to female Swiss mice (n=5-6). Control animals (n=3) were treated with phosphate buffered saline (PBS). ML-Magh sample effects were investigated from 30 minutes until 30 days after the administration. The viability of peritoneal cells was not affected by the ML-Magh treatment, as investigated by two different methods: nigrosin dye exclusion and propidium iodide exclusion. The leukocytes cytometry indicated that ML-Magh has no pro-inflammatory action. The eosinophil population presented an increase one hour after ML-Magh administration, suggesting a slight allergic process. Absence of genotoxicity and cytotoxicity was confirmed by micronucleus test and polychromatic erythrocyte percentage, respectively. The histopathology analysis performed in three tissues showed few particle clusters in the lungs and spleen. Clusters were not observed in the liver. No morphological alterations were found in these tissues during all the experimental time. The rare inflammatory infiltration observed in the liver and lungs of ML- Magh-treated mice was also observed in control animals. Biochemical blood tests showed irrelevant alterations. Concentrations of alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, and creatinine were constant almost all over the experiment, suggesting no hepatic or splenic injury. The levels of serum iron were not affected by ML-Magh treatment. Nevertheless, serum iron levels are dose-dependent. Data suggest that the investigated sample is biocompatible and it has potential to be used in biomedical applications, especially as agents for anticancer therapy through magnetohyperthermia and drug delivery systems.

ASSUNTO(S)

magnetic nanoparticles nanopartículas magnéticas magnetolipossomas magnetoliposomes nanobiotecnologia nanotoxicologia nanotoxicology biocompatibility nanobiotechnology biologia molecular biocompatibilidade

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