Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti-Candida albicans Activity of Amphotericin B Using an Immunocompetent Murine Model.

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 IC50 and the MIC90 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.

• Authors: Tiphany Grisin, Christian Bories, Martina Bombardi, Philippe M Loiseau, Valérie Rouffiac, Audrey Solgadi, Jean-Maurice Mallet, Gilles Ponchel, Kawthar Bouchemal
• Journal: Pharmaceutical research (Pharm Res) Vol. 34 Issue 5 Pg. 1067-1082 (05 2017) ISSN: 1573-904X [Electronic] United States
• PMID: 28168390 (Publication Type: Journal Article)

Chemical References

• Antifungal Agents
• Drug Combinations
• Hydrogels
• alpha-Cyclodextrins
• Deoxycholic Acid
• Poloxamer
• Amphotericin B
• amphotericin B, deoxycholate drug combination
• Chitosan
• alpha-cyclodextrin

Topics

• Amphotericin B (chemistry, pharmacology)
• Animals
• Antifungal Agents (chemistry, pharmacology)
• Blood Platelets (chemistry)
• Candida albicans (drug effects)
• Candidiasis (drug therapy)
• Chemistry, Pharmaceutical (methods)
• Chitosan (chemistry, pharmacology)
• Deoxycholic Acid (chemistry, pharmacology)
• Disease Models, Animal
• Drug Combinations
• Female
• Hydrogels (chemistry, pharmacology)
• Mice
• Mice, Inbred BALB C
• Mucous Membrane (drug effects)
• Nanoparticles (chemistry)
• Poloxamer (chemistry)
• Swine
• alpha-Cyclodextrins (chemistry)