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- Title
Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti- Candida albicans Activity of Amphotericin B Using an Immunocompetent Murine Model.
- Authors
Grisin, Tiphany; Bories, Christian; Bombardi, Martina; Loiseau, Philippe; Rouffiac, Valérie; Solgadi, Audrey; Mallet, Jean-Maurice; Ponchel, Gilles; Bouchemal, Kawthar
- Abstract
Purpose: The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti- Candida albicans activity. Methods: Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water. The formulation is specifically-engineered for mucosal application by dispersing chitosan micro-platelets into thermosensitive pluronic F127 20 wt% hydrogel. Results: The formulation completely cured C. albicans vaginal infection in mice and had a superior activity in comparison with AmB-DOC without addition of chitosan micro-platelets. In vitro studies showed that the platelets significantly enhance AmB-DOC antifungal activity since the IC and the MIC decrease 4.5 and 4.8-times. Calculation of fractional inhibitory concentration index (FICI = 0.198) showed that chitosan micro-platelets act in a synergistic way with AmB-DOC against C. albicans. No synergy is found between spherical nanoparticles composed poly(isobutylcyanoacrylate)/chitosan and AmB-DOC. Conclusion: These results demonstrate for the first time the ability of flattened chitosan micro-platelets to have synergistic activity with AmB-DOC against C. albicans candidiasis and highlight the importance of rheological and mucoadhesive behaviors of hydrogels in the efficacy of the treatment.
- Subjects
AMPHOTERICIN B; CANDIDA albicans; CHITOSAN; HYDROGELS; VAGINAL disease treatment; LABORATORY mice; THERAPEUTICS
- Publication
Pharmaceutical Research, 2017, Vol 34, Issue 5, p1067
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-017-2117-3