Stability, biological and biopharmaceutical evaluation of the inclusion complexes of the antifungal and antiprotozoal drug candidate 2-(2-nitrovinyl) furan (G-0) with beta cyclodextrin derivatives

Autor: Iracilda Zeppone Carlos, Antonio Carlos Bergamaschi Tercini, Taís Maria Bauab, Guy Van den Mooter, Matheus Aparecido dos Santos Ramos, Mirtha Mayra González Bedia, Vivian Ruz Sanjuan, Anselmo Gomes de Oliveira
Přispěvatelé: Universidade Estadual Paulista (Unesp), University of Leuven (KULeuven), Central University of Las Villas
Rok vydání: 2020
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1773-2247
DOI: 10.1016/j.jddst.2020.101767
Popis: Made available in DSpace on 2020-12-12T02:05:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01 Universidad Nacional de Salta Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The purpose of this work was to evaluate the inclusion complexes (ICs) of 2-(2-nitrovinyl) furan (G-0) with hydroxypropyl and sulfobutylether-β-cyclodextrin intended for drug stabilization. The freeze-dried ICs were subjected to an accelerated stability study, monitored by HPLC-DAD and GC-MS methods. Drug sublimation/volatility has been analyzed through Thermogravimetric Analysis and Headspace Gas Chromatography. Drug dissolution profile in Simulated Vaginal Fluid (SVF) and permeation/retention in bovine vaginal mucosa were also evaluated. The influence of ICs on the “in vitro” antifungal activity against Candida spp. was investigated through Broth Microdilution Method and the cytotoxicity on fibroblasts and keratinocytes, through MTT assay protocol. ICs ensured an optimum drug chemical stability under accelerated conditions and significantly decreased the drug sublimation/volatilization compared with free G-0 and physical mixtures. Both complexes allowed a fast drug release in SVF, but G-0 was not quantified in the receptor compartment, although it was recovery from the mucosa, without significant influence on the complex formation. ICs maintained the antifungal activity against Candida albicans but improved the drug activity against a Candida krusei resistant strain (ICs MIC = 12.5 μg mL−1, G-0 MIC = 25 μg mL−1, Amphotericin B MIC = 20 μg mL−1). Cytotoxicity on fibroblast and keratinocytes followed the ranking order: G-0 > FD G-0/HP-β-CD > FD G-0/SBE-β-CD. São Paulo State University (UNESP) School of Pharmaceutical Sciences, Rodovia Araraquara-Jau, km 01 Drug Delivery and Disposition Department of Pharmaceutical and Pharmacological Sciences University of Leuven (KULeuven), O&N2 Herestraat 49-Box 921 São Paulo State University (UNESP) Center for Monitoring and Research Quality of Fuels Biofuels Petroleum and Derivatives (CEMPEQC) Chemistry Institute, Rua Prof. Francisco Degni 55 Pharmacy Department Chemistry and Pharmacy Faculty Central University of Las Villas, Carretera a Camajuaní km 5 ½ São Paulo State University (UNESP) School of Pharmaceutical Sciences, Rodovia Araraquara-Jau, km 01 São Paulo State University (UNESP) Center for Monitoring and Research Quality of Fuels Biofuels Petroleum and Derivatives (CEMPEQC) Chemistry Institute, Rua Prof. Francisco Degni 55 CAPES: 001
Databáze: OpenAIRE
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