Magnetic nanotechnology for diclofenac remediation: molecular basis of drug adsorption and neurobehavioral toxicology as a preliminary study for safe application.

Diclofenac is a commercial non-steroidal anti-inflammatory drug commonly present as a pollutant in naturally occurring water sources and wastewaters. In this work, the adsorption of diclofenac onto chitosan-coated magnetic nanosystems is proposed as a possible tool for remediation. Experimental and theoretical studies have been carried out to reveal the mechanisms associated with diclofenac interactions among all the components of the nanosystem. Mechanisms are presented, analyzed and discussed. A toxicological study in mice was carried out to evaluate the parameters associated with neurotoxicity of the nanodevice. The elucidation of the mechanisms implied in the adsorption process of diclofenac onto magnetic chitosan nanocomposites suggests that diclofenac remediation from water is possible by adsorption onto chitosan. The strategy innovates the commonly used methodologies for diclofenac remediation from pharmaceutical wastes. This magnetic nanotechnology would not induce damage on the nervous system in a murine model, in case of traces remaining in water sources.

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

A simple two-step drug encapsulation method was developed to obtain biocompatible magnetic nanocarriers for the potential targeted treatment of diverse diseases. The nanodevice consists of a magnetite core 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 quantification are further addressed. This multi-disciplinary study aims to elucidate the toxicological impact of the MNPs at hematological, vascular, neurological and behavioral levels. Blood compatibility assays revealed that MNPs 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 induce morphological changes in blood cells. Platelet aggregation was not affected by MNPs either and just a slight diminution was observed with Dic-Chit@MNPs, an effect possibly due to diclofenac. The examined formulations did not exert cytotoxicity on rat aortic endothelial cells and no changes in cell viability or their capacity to synthesize NO were observed. Behavioral and functional nervous system parameters in a functional observational battery were assessed after a subacute treatment of mice with Chit@MNPs. The urine pools of the exposed group were decreased. Nephritis and an increased number of megakaryocytes in the spleen were observed in the histopathological studies. Sub-acute exposure to Chit@MNPs did not produce significant changes in the parameters used to evaluate neurobehavioral toxicity. The aspects focused on within this manuscript are relevant at the pre-clinical level providing new and novel knowledge concerning the biocompatibility of magnetic nanodevices for biomedical applications.

Tetra-kis[µ-2-(3-phenoxy-phen-yl)propionato-κO:O']bis-[(dimethyl-formamide-κO)copper(II)].

The title compound, [Cu(2)(C(15)H(13)O(3))(4)(C(3)H(7)NO)(2)], is formed by the chelate coordination of four racemic fenoprofenate (fenoprofenate is 2,3-phenoxyphenyl propionate) anions and two dimethyl-formamide mol-ecules to two copper(II) ions, building a paddle-wheel dinuclear mol-ecule. The distorted square-pyramidal coordination of each Cu(II) atom is made up of four O atoms of the four fenoprofenate units and another O atom from a dimethyl-formamide mol-ecule. The two enanti-omeric forms of the fenoprofenate anions are present in the complex, in an optically inactive centrosymmetric arrangement.