Physicochemical characterization and in vitro biological evaluation of solid compounds from furazolidone-based cyclodext
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ORIGINAL ARTICLE
Physicochemical characterization and in vitro biological evaluation of solid compounds from furazolidone-based cyclodextrins for use as leishmanicidal agents Suzana Gonçalves Carvalho 1,2 & Daniel Fernandes Cipriano 3 & Jair Carlos Checon de Freitas 3 & Miguel Ângelo Schettino Junior 3 & Enrique Ronald Yapuchura Ocaris 3 & Carolina Bioni Garcia Teles 4,5,6 & Aurileya de Jesus Gouveia 4 & Ricardo Pereira Rodrigues 7 & Marcos Santos Zanini 2 & Janaína Cecília Oliveira Villanova 2,8
# Controlled Release Society 2020
Abstract The discovery of new drugs and dosage forms for the treatment of neglected tropical diseases, such as human and animal leishmaniasis, is gaining interest in the chemical, biological, pharmaceutical, and medical fields. Many pharmaceutical companies are exploring the use of old drugs to establishing new drug dosage forms and drug delivery systems, in particular for use in neglected diseases. The formation of complexes with cyclodextrins is widely used to improve the stability, solubility, and bioavailability of pharmaceutical drugs, as well as reduce both the toxicity and side effects of many of these drugs. The aim of this study was to characterize solid compounds obtained from the association between furazolidone (FZD) and β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD). The solid compounds were prepared in molar ratios of 1:1 and 1:2 (drug:CD) by kneading and lyophilization. Molecular docking was used to predict the preferred relative orientation of FZD when bound in both studied cyclodextrins. The resulting solid compounds were qualitatively characterized by scanning electron microscopy (SEM), thermal analysis (DSC and TG/DTG), X-ray diffraction (XRD), Raman spectroscopy with image mapping (Raman mapping), and 13C nuclear magnetic resonance spectroscopy (13C NMR) in the solid state. The cytotoxicity of the compounds against THP-1 macrophages and the 50% growth inhibition (IC50) against Leishmania amazonensis promastigote forms were subsequently investigated using in vitro techniques. For all of the solid compounds obtained, the existence of an association between FZD and CD were confirmed by one or more characterization techniques (TG/DTG, DSC, SEM, XRD, RAMAN, and 13C NMR), particularly by a significant decrease in the crystallinity of these materials and a reduction in the melting enthalpy associated with furazolidone thermal events. The formation of more effective interactions occurred in the compounds prepared by lyophilization, in a 1:2 molar ratio of the two CDs studied. However, the formation of an inclusion complex was confirmed only for the solid compound obtained from HP-β-CD prepared by lyophilization (LHFZD1:2). The absence of cytotoxicity on the THP-1 macrophage lineages and the leishmanicidal activity were confirmed for all compounds. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13346-020-00841-1) contains supplementary material, which is available to authorized users. * Suzana Gonçalves Carvalho
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