title: Improved yeast delivery of fluconazole with a nanostructured lipid carrier system.
abstract: Despite the growing trends in the number of patients at risk for invasive fungal infections, management with current antifungal agents results in complications due to changes in the epidemiology and drug susceptibility of invasive fungal infections. In the present research fluconazole-loaded nanostructured lipid carriers were prepared using probe ultrasonication techniques and investigated the efficacy of the optimal formulation on a large number of Candida species. The morphology of the obtained nanostructured lipid carriers was characterized by transmission-electron microscopy. The minimum inhibitory concentrations (MIC) for the new formulations against strains of Candida were investigated using the Clinical and Laboratory Standards Institute document M27-A3 and M27-S4 as a guideline. The fluconazole-loaded nanostructured lipid carriers presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 126.4±15.2nm, -35.1±3.0mV, and 93.6±3.5%, respectively. The drug release from fluconazole-loaded nanostructured lipid carriers exhibited burst-release behavior at the initial stage followed by sustained release over 24h. Using a new formulation of fluconazole led to a significant decrease in MICs for all Candida groups (P<0.05). Furthermore, C. albicans isolates showed more susceptibility to fluconazole-loaded nanostructured lipid carriers than C. glabrata and C. parapsilosis (P<0.05). The MIC50drug concentration was obtained as 0.0625, 0.031 and 0.25μg/ml for fluconazole-resistant strains of C. albicans, C. glabrata, and C. parapsilosis, respectively. In conclusion, a novel delivery system which can be used as part of a strategy to improve the antifungal activity of fluconazole against various Candida strains with different susceptibilities to conventional formulations of fluconazole was evaluated.
authors.affiliation: Student Research Committee Center, Mazandaran University of Medical Sciences, Sari, Iran; Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Kelidari
authors.affiliation: Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: moazeni.maryam@gmail.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moazeni
authors.affiliation: Student Research Committee Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Roghayeh
authors.initials: R
authors.lastname: Babaei
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Saeedi
authors.affiliation: Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Akbari
authors.affiliation: Educational Development Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Parisa Islami
authors.initials: PI
authors.lastname: Parkoohi
authors.affiliation: Student Research Committee Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Nabili
authors.affiliation: Student Research Committee Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Atefeh Abdollahi
authors.initials: AA
authors.lastname: Gohar
authors.affiliation: Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Morteza-Semnani
authors.affiliation: Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Brighton BN1 9QJ, UK; Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: a.nokhodchi@sussex.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002175:Candida / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D015725:Fluconazole / Q000008:administration & dosage* / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D008055:Lipids; D015725:Fluconazole
keywords: Candida; Drug delivery; Fluconazole; Nanostructured lipid carrier