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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 IC50 and MIC90 of 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.
AuthorsTiphany Grisin, Christian Bories, Philippe M Loiseau, Kawthar Bouchemal
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 519 Issue 1-2 Pg. 381-389 (Mar 15 2017) ISSN: 1873-3476 [Electronic] Netherlands
PMID28130196 (Publication Type: Journal Article)
CopyrightCopyright © 2017 Elsevier B.V. All rights reserved.
Chemical References
  • Antifungal Agents
  • Cyclodextrins
  • Drug Combinations
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination
  • Chitosan
Topics
  • Amphotericin B (chemistry, pharmacology)
  • Animals
  • Antifungal Agents (chemistry, pharmacology)
  • Candida glabrata (drug effects)
  • Candidiasis (drug therapy, microbiology)
  • Chitosan (chemistry)
  • Cyclodextrins (chemistry, pharmacology)
  • Deoxycholic Acid (pharmacology)
  • Drug Combinations
  • Immunocompromised Host (drug effects)
  • Mice
  • Mucous Membrane (microbiology)

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