title: Cyclodextrin-mediated self-associating chitosan micro-platelets act as a drug booster against Candida glabrata mucosal infection in immunocompetent mice.
abstract: This study reports design and evaluation of chitosan-based microparticle activity against Candida glabrata in vitro and in vivo in immunocompetent mice model artificially maintained in oestrus state. Because their flattened shape, chitosan microparticles are called here micro-platelets. They were obtained by self-association of oleoyl chitosan and α-cyclodextrin in water. A mixture of amphotericin B-deoxycholate (Fungizone®, AmB-DOC) and chitosan micro-platelets gelified with pluronic®F127 (20wt%) completely cured C. glabrata vaginal infection. Colony factor unit counting and mycological analysis of mice vaginal mucosa after Grocott-Gomori methenamine-silver staining confirmed the absence of C. glabrata. Furthermore, in vitro evaluations revealed that IC50and MIC90of AmB-DOC were decreased 1.8 and 1.4-times respectively when associated with chitosan micro-platelets. Neither native chitosan nor oleoyl chitosan allowed improvement in AmB-DOC anti-C. glabrata activity. This work demonstrates for the first time that a simple mixing of chitosan micro-platelets with AmB-DOC enhanced its anti-C. glabrata activity.
authors.affiliation: Institut Galien Paris Sud, UMR CNRS 8612, Univ. Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5, rue J-B. Clément, 92296, Châtenay-Malabry, France.
authors.forename: Tiphany
authors.initials: T
authors.lastname: Grisin
authors.affiliation: BioCIS « Biomolécules: Conception, Isolement, Synthèse » - « Chimiothérapie Antiparasitaire », UMR CNRS 8076, Univ. Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5, rue J.B. Clément, 92296, Châtenay-Malabry Cedex, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Bories
authors.affiliation: BioCIS « Biomolécules: Conception, Isolement, Synthèse » - « Chimiothérapie Antiparasitaire », UMR CNRS 8076, Univ. Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5, rue J.B. Clément, 92296, Châtenay-Malabry Cedex, France.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.affiliation: Institut Galien Paris Sud, Junior member of the Institut Universitaire de France, UMR CNRS 8612, Univ. Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5, rue J-B. Clément, 92296, Châtenay-Malabry, France. Electronic address: kawthar.bouchemal@u-psud.fr.
authors.forename: Kawthar
authors.initials: K
authors.lastname: Bouchemal
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D041221:Candida glabrata / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D048271:Chitosan / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004338:Drug Combinations; D016867:Immunocompromised Host / Q000187:drug effects*; D051379:Mice; D009092:Mucous Membrane / Q000382:microbiology*
chemical_list: D000935:Antifungal Agents; D003505:Cyclodextrins; D004338:Drug Combinations; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D048271:Chitosan
keywords: Amphotericin B; Candida glabrata; Chitosan; Cyclodextrin; Micro-platelets; Self-assembly