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. 2023 May 8;15(5):1436.
doi: 10.3390/pharmaceutics15051436.

Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel

Maria Lajarin-Reinares  1   2 , Iria Naveira-Souto  2 , Mireia Mallandrich  3 , Joaquim Suñer-Carbó  3 , Montserrat Llagostera Casas  1 , Maria Angels Calvo  4 , Francisco Fernandez-Campos  5
Affiliations

Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel

Maria Lajarin-Reinares et al. Pharmaceutics. .

Abstract

Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis.

Keywords: ATP-binding cassette; Candida spp.; disulfiram; mucoadhesion; resistant; vaginitis.

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Conflict of interest statement

M.L.-R. and I.N.-S. are employees of Laboratory Reig Jofre. They belong to the R&D department and do not participate in marketing or commercial activities. The data presented were conducted under general good laboratory practices. The other authors do not declare any conflicts of interest.

Figures

Figure 1
Figure 1
Schematic illustration of the device for evaluating adhesive strength.
Figure 2
Figure 2
Schematic of the device used to measure the mucoadhesive properties.
Figure 3
Figure 3
Matrix plots explaining the relationships between the different variables.
Figure 4
Figure 4
Plots of the main effects of PEG-90M and carrageenan on the mucoadhesive properties of the gels.
Figure 5
Figure 5
(A) Plots of the main effects of PEG-90M and carrageenan on the viscosity (mPa×s) of the gels. (B) Viscosity interaction point.
Figure 6
Figure 6
(A) Plots of the main effects of PEG-90M and carrageenan on fluorescein adhesion. (B) Fluorescein adhesion interaction plot.
Figure 7
Figure 7
(A) Shear stress vs. shear rate (red) and viscosity vs. shear rate (blue) curves of the placebo formulation. (B) Shear stress vs. shear rate (red) and viscosity vs. shear rate (blue) curves of the placebo formulation with SVF.
Figure 8
Figure 8
Storage modulus, loss modulus, and phase angle during the sweep stress test on the mucoadhesive gel 24 h after preparation at a frequency of 1 s−1. (A) Placebo Gel. (B) Placebo Gel with SVF.
Figure 9
Figure 9
Release of disulfiram from the 0.5% gel and from the 1% gel. Mean of the quantities released of D expressed as a percentage respect total amount seeded from the 0.5% gel and from the 1% gel after 6 h in vitro.
Figure 10
Figure 10
Pig vagina permeation profiles after administration of the 0.5% and 1% D gels (n = 4).
See this image and copyright information in PMC

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