Gallic acid/hydroxypropyl-β-cyclodextrin complex: Improving solubility for application on in vitro/ in vivo Candida albicans biofilms

Guilherme Rodrigues Teodoro; Aline Vidal Lacerda Gontijo; Aline Chiodi Borges; Márcia Hiromi Tanaka; Gabriela de Morais Gouvêa Lima; Marcos José Salvador; Cristiane Yumi Koga-Ito

doi:10.1371/journal.pone.0181199

Gallic acid/hydroxypropyl-β-cyclodextrin complex: Improving solubility for application on in vitro/ in vivo Candida albicans biofilms

PLoS One. 2017 Jul 11;12(7):e0181199. doi: 10.1371/journal.pone.0181199. eCollection 2017.

Authors

Guilherme Rodrigues Teodoro¹, Aline Vidal Lacerda Gontijo^{2

3}, Aline Chiodi Borges^{1

2}, Márcia Hiromi Tanaka^{1

2}, Gabriela de Morais Gouvêa Lima^{1

2}, Marcos José Salvador³, Cristiane Yumi Koga-Ito^{1

2}

Affiliations

¹ Oral Biopathology Graduate Program, São José dos Campos Institute of Science and Technology, Universidade Estadual Paulista/UNESP, São José dos Campos, SP, Brazil.
² Departament of Environmental Engineering, São José dos Campos Institute of Science and Technology, Universidade Estadual Paulista/UNESP, São José dos Campos, SP, Brazil.
³ Department of Plant Biology, Institute of Biology, Universidade Estadual de Campinas/UNICAMP, Campinas, SP, Brazil.

Abstract

The aim of this study was to increase the solubility of gallic acid (GA) for the treatment of Candida albicans biofilm, which is very difficult to treat and requires high drug concentrations. Cyclodextrins (CDs) were used for this purpose. Complexes were evaluated by phase-solubility studies, prepared by spray drying and characterized by drug loading, scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The complexes were tested on C. albicans biofilm using in vitro and in vivo models. HPβCD formed soluble inclusion complexes with GA. The percentage of GA in GA/HPβCD was 10.8 ± 0.01%. The SEM and DSC analyses confirmed the formation of inclusion complexes. GA/HPβCD maintained the antimicrobial activity of the pure GA. GA/HPβCD was effective on C. albicans biofilms of 24 and 48h. The in vivo results showed an anti-inflammatory activity of GA/HPβCD with no difference in invading hypha counting among the groups. This study encourages the development of new antifungal agents.

MeSH terms

2-Hydroxypropyl-beta-cyclodextrin
Biofilms / drug effects*
Calorimetry, Differential Scanning
Candida albicans / drug effects*
Candida albicans / ultrastructure
Cyclodextrins / chemistry
Gallic Acid / chemistry*
Gallic Acid / pharmacology*
Microscopy, Electron, Scanning
Solubility
beta-Cyclodextrins / chemistry*

Substances

Cyclodextrins
beta-Cyclodextrins
2-Hydroxypropyl-beta-cyclodextrin
Gallic Acid

Grants and funding

This study was supported by grant #2013/00037-1, São Paulo Research Foundation (FAPESP). GR Teodoro (#2012/16805-5), AVL Gontijo (#2014/09666-4), AC Borges, (#2014/02354-7), MH Tanaka (#2014/13469-0) and GMG Lima (#2015/03470-3) are supported by FAPESP. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report and in the decision to submit the article for publication.