title: Time to overcome fluconazole resistant Candida isolates: Solid lipid nanoparticles as a novel antifungal drug delivery system.
abstract: Antifungal therapy results in complications in management due to changes in the patterns of epidemiology and drug susceptibility of invasive fungal infections. In this study, we prepared fluconazole-loaded solid lipid nanoparticles (FLZ-SLNs) and investigated the efficacy of the optimal formulation on fluconazole (FLZ)-resistant strains of several Candida species. FLZ-SLN was produced using probe ultrasonication techniques. The morphology of the obtained SLNs was characterized by field emission scanning electron microscopy. The minimum inhibitory concentrations for the new formulations against fluconazole-resistant strains of Candida were investigated using CLSI document M27-A3. The FLZ-SLNs presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 84.8nm, -25mV and 89.6%, respectively. The drug release from FLZ-SLNs exhibited burst release behaviour at the initial stage (the first 30min) followed by a sustained release over 24h FLZ-resistant yeast strains behaved as susceptible strains after treatment with FLZ-SLNs (≤8μg/ml). The MIC50 drug concentrations were 2μg/ml, 1μg/ml and 2μg/ml for FLZ-resistant strains of Candida albicans, Candida parapsilosis and Candida glabrata, respectively. In this study, we evaluated novel delivery systems for combating Candida strains that exhibit low susceptibility against the conventional formulation of FLZ as a first-line treatment.
authors.affiliation: Invasive Fungi Research Centre (IFRC)/Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moazeni
authors.affiliation: Pharmaceutical Research Centre, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: hamidreza.kelidari@yahoo.com.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Kelidari
authors.affiliation: Department of Pharmaceutics, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Saeedi
authors.affiliation: Department of Pharmaceutics, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Ketayoun
authors.initials: K
authors.lastname: Morteza-Semnani
authors.affiliation: Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran; Iranian Social Security Organization,Mazandaran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Nabili
authors.affiliation: Invasive Fungi Research Centre (IFRC)/Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Atefeh Abdollahi
authors.initials: AA
authors.lastname: Gohar
authors.affiliation: Department of Pharmaceutics, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Akbari
authors.affiliation: Department of Medical Mycology and Parasitology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ensieh
authors.initials: E
authors.lastname: Lotfali
authors.affiliation: Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Brighton BN1 9QJ, UK; Drug Applied Research Centre and Faculty of Pharmacy, Tabriz Medical Sciences University, Tabriz, Iran. Electronic address: a.nokhodchi@sussex.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D041221:Candida glabrata / Q000187:drug effects / Q000254:growth & development; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D005227:Fatty Acids / Q000737:chemistry; D015725:Fluconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D013010:Sonication; D013229:Stearic Acids / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D005227:Fatty Acids; D013229:Stearic Acids; C086409:glyceryl behenate; C031183:stearic acid; D015725:Fluconazole
keywords: Candida; Fluconazole; Resistance; Solid lipid nanoparticles