Magnetic nanoparticles for drug targeting: from design to insights into their systematic toxicity. Preclinical evaluation of hematological, vascular and neurobehavioral toxicology

M.AGOTEGARAY; ADRIÁN CAMPELO; ROBERTO ZYSLER; FERNANDA GUMILAR; CRISTINA BRAS; ARIEL GANDINI; ALEJANDRA MINETTI; VIRGINIA MASSHEIMER; VERÓNICA LASSALLE

Biomaterials Science

RCS

Año: 2017

2047-4849

A simple two-step drug encapsulation method was developed to obtain biocompatible magnetic nanocarriersfor the potential targeted treatment of diverse diseases. The nanodevice consists of a magnetitecore coated with chitosan (Chit@MNPs) as a platform for diclofenac (Dic) loading as a model drug (Dic?Chit@MNPs). Mechanistic and experimental conditions related to drug incorporation and quantificationare further addressed. This multi-disciplinary study aims to elucidate the toxicological impact of the MNPsat hematological, vascular, neurological and behavioral levels. Blood compatibility assays revealed thatMNPs did not affect either erythrosedimentation rates or erythrocyte integrity at the evaluated doses(1, 10 and 100 μg mL−1). A microscopic evaluation of blood smears indicated that MNPs did not inducemorphological changes in blood cells. Platelet aggregation was not affected by MNPs either and just aslight diminution was observed with Dic?Chit@MNPs, an effect possibly due to diclofenac. The examinedformulations did not exert cytotoxicity on rat aortic endothelial cells and no changes in cell viability ortheir capacity to synthesize NO were observed. Behavioral and functional nervous system parameters in afunctional observational battery were assessed after a subacute treatment of mice with Chit@MNPs. Theurine pools of the exposed group were decreased. Nephritis and an increased number of megakaryocytesin the spleen were observed in the histopathological studies. Sub-acute exposure to Chit@MNPs did notproduce significant changes in the parameters used to evaluate neurobehavioral toxicity. The aspectsfocused on within this manuscript are relevant at the pre-clinical level providing new and novel knowledgeconcerning the biocompatibility of magnetic nanodevices for biomedical applications.