title: Liposomal thymoquinone effectively combats fluconazole-resistant Candida albicans in a murine model.
abstract: The aim of the present study was to develop a novel liposomal formulation of thymoquinone (TQ) to treat fluconazole-susceptible and -resistant Candida albicans (C. albicans) infections. The liposomal preparation of TQ (Lip-TQ) was used against a fluconazole-susceptible or -resistant isolate of C. albicans. Various doses of fluconazole (0, 5, 10, 20 and 40 mg/kg) or free TQ or Lip-TQ (0, 1, 2 and 5mg/kg) were used to treat C. albicans infected mice. Mice were observed for 40 days post C. albicans infection, and their kidneys were assessed for the fungal load. Fluconazole showed anti-fungal activity against the drug-susceptible, but not against the -resistant isolate of C. albicans. Free TQ showed its activity against both fluconazole-susceptible or -resistant C. albicans, however, Lip-TQ was found to be the most effective and imparted ∼ 100% and ∼ 90% survival of mice infected with fluconazole-susceptible and -resistant isolates of C. albicans, respectively. Mice treated with Lip-TQ showed highly reduced severity of infection in their tissue homogenates. Therefore, Lip-TQ may effectively be used in the treatment of C. albicans infections, including those which are not responding to fluconazole.
authors.affiliation: Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia.
authors.forename: Masood Alam
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia.
authors.forename: Ahmad N
authors.initials: AN
authors.lastname: Aljarbou
authors.affiliation: Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia.
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India. Electronic address: hinayounus@rediffmail.com.
authors.forename: Hina
authors.initials: H
authors.lastname: Younus
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016227:Benzoquinones / Q000008:administration & dosage*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology*; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D008081:Liposomes / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D016227:Benzoquinones; D008081:Liposomes; D015725:Fluconazole; C003466:thymoquinone
keywords: Drug delivery; Fluconazole-resistant; Systemic candidiasis; Thymoquinone