No abstract

A síntese, a caracterização físico-química, as propriedades anti-inflamatórias e a atividade mimética de catecolase do complexo de cobre(II) com a droga anti-inflamatória non-esteroidal Fenoprofeno [ácido 2-(3-fenóxifenil)propiônico] com fórmula [Cu 2 (fen) 2 (dmf) 2 ] (fen = ânion do fenoprofenato, dmf = N,N-dimetilformamida) foram investigadas. Os resultados da análise espectroscópica (espectros de FTIR e EPR) e dados de análise termogravimétrica e térmica diferencial obtidos para o complexo sólido estão de acordo com a sua estrutura dinuclear. Os espectros eletrônicos do produto são igualmente apresentados e discutidos neste trabalho. O complexo foi testado para as suas propriedades anti-inflamatórias em comparação com a droga de referência, o sal de cálcio do Fenoprofeno. A administração oral do composto binuclear inibiu o desenvolvimento do edema induzido por carragenana em ratos; esta inibição foi mais significativa do que a obtida com a droga de referência. O estudo cinético da atividade mimética da catecolase foi realizado espectrofotometricamente, monitorando-se a transformação oxidativa do 3,5-di-terc-butilcatecol na o-quinona correspondente. Os parâmetros cinéticos foram determinados pelo emprego do modelo de Michaelis-Menten, que demonstrou que o novo complexo mimetiza a atividade da catecol oxidase.The synthesis, physicochemical characterization, anti-inflammatory properties and catecholase mimetic activity of the dinuclear complex of copper(II) with the non-steroidal anti-inflammatory drug Fenoprofen [2-(3-phenoxyphenyl)propionic acid] with formula [Cu 2 (fen) 4 (dmf) 2 ] (fen = fenoprofenate anion, dmf = N,N-dimethylformamide) have been investigated. Results of spectroscopic analysis (FTIR and EPR) as well as thermogravimetric and differential thermal analysis data obtained for the solid complex are in good agreement with its dinuclear structure. Electronic spectra of the product are also reported and discussed. The complex was tested for anti-inflammatory properties in comparison to the parent drug, Fenoprofen calcium salt. Oral administration of the dinuclear compound inhibited development of carrageenan-induced oedema in mice; this inhibition was higher than that observed for the parent drug. The kinetic study of the catecholase mimetic activity was carried out spectrophotometrically by monitoring the oxidative transformation of 3,5-di-tert-butylcatechol into the corresponding light-absorbing o-quinone. Kinetic parameters were determined employing the Michaelis-Menten model, showing that the new complex presents catechol oxidase mimetic activity.Keywords: copper(II), Fenoprofen, anti-inflammatory properties, catecholase activity IntroductionThe proposed curative properties of copper(II) carboxylate-based non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous mononuclear and dinuclear copper(II) complexes of NSAIDs with enhanced anti-inflammatory activity.1,2 The elevation of total blood copper levels during acute as well as chronic inflammatory states has been re...

New magnetic devices consisting of magnetite functionalized with oleic acid and chitosan have been synthesized and employed to the loading of Diclofenac as potential tool for treatment of targeted inflammatory diseases. Magnetic loaded and un-loaded nanoparticles have been thoroughly characterized by infrared spectroscopy, transmission electron microscopy, determination of hydrodynamic diameter by Dynamic light scattering and zeta potential measurements at different pH conditions. A study of the release of Diclofenac has been performed in vitro and available mathematical models have been used to determine the release kinetic. Both properties and release data reveal that this nanomagnetic platform would be suitable for in vivo assays.

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). 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.