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

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.

Effects of Acetone Fraction From Buchenavia tomentosa Aqueous Extract and Gallic Acid on Candida albicans Biofilms and Virulence Factors

“…This points out to a promising antifungal activity of AF. For comparative purposes, all the data corresponding to GA 2X MIC and AmB (2 μg ml -1 ) were extracted from another study performed by our group ( Teodoro et al, 2017 ). It is important to highlight that all these experiments were performed simultaneously.…”

“…∗ P < 0.05, ∗∗∗ P < 0.0001; ns, not statistically significant. Ψ: Data collected from Teodoro et al (2017) . Tests were performed in triplicate in three independent experiments using C. albicans ATCC 18804, SC5314 and three clinical strains ( n = 45 for each group).…”

“…For GA, only one concentration (2X the MIC) was used, since 4X the MIC (i.e., 20 mg ml -1 ) is insoluble in water ( Srinivas et al, 2010 ). A study performed by our group ( Teodoro et al, 2017 ) improved the GA solubility using cyclodextrins, which increase the aqueous solubility. These molecules present a lipophilic cavity that hosts the water insoluble drug, and a hydrophilic exterior, which increases the aqueous solubility.…”

“…Surprisingly, GA at 2X MIC was able to reduce the 48 h-biofilm ( Figure 2 ), without effect on the 24 h-biofilm. The authors previously hypothesized ( Teodoro et al, 2017 ) that this phenomenon could be due to the dynamics of biofilm formation. In the biofilm of 24 h, the composition of cells, molecular structures, and water are different from the biofilm of 48 h, which could interfere on the efficiency of GA. Additionally, still according to Teodoro et al (2017) , GA might act on matrix compounds of biofilms, which are quantitatively more present in the 48 h biofilms.…”

Repurposing Common Food Additives (Benzo Derivatives) As New Anti-parasitic Agents

“…Of note, methods have been developed for the enhancement of bioavailability or biologically relevant application of GA. For example, to improve GA solubility for treating C. albicans biofilms, antifungal efficacy of GA/hydroxypropyl-β-cyclodextrin complex (HPβCD) has been examined (Teodoro et al, 2017). Results showed that GA/HPβCD complex was active against C. albicans biofilms, where the complex preserved the antifungal potency of the pure GA while it also exerted anti-inflammatory activity.…”