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Cited by 2Advanced Drug Delivery SystemsAntifungal resistance and susceptibilityHydrogels: synthesis, properties, applications

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

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Lajarin-Reinares, Maria, Naveira-Souto, Iria, Mallandrich, Mireia, Suñer-Carbó, Joaquim, Llagostera Casas, Montserrat, Calvo, Maria Angels, Fernandez-Campos, Francisco·2023·Pharmaceutics
DOI 10.3390/pharmaceutics15051436PMC PMC10223105
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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.

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  • DIS disrupts key fungal cell processes and exhibits potent antifungal activity against Candida and Cryptococcus species by inhibiting both growth and biofilm formation.

    “DIS disrupts key fungal cell processes (metabolism, replication, and membrane transport), exhibiting potent antifungal activity against Candida and Cryptococcus species by inhibiting both growth and biofilm formation.111,112,113”

    From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [112]

    The Results and Discussion (§3.1; page unavailable) report that disulfiram inhibited the growth of three tested Candida species at 2–8 µg/mL, and discuss possible effects on metabolic pathways and drug transport. The paper does not establish disruption of replication or inhibition of biofilm formation, and its susceptibility tests did not include Cryptococcus. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • DIS's antifungal effects arise from inactivating key enzymes, including ALDH, urease, and carbamate kinase.

    “DIS’s antifungal effects arise from inactivating key enzymes, including ALDH, urease (URE), and carbamate kinase (CK).”

    From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [112]

    The Introduction says disulfiram inhibits ALDH in its treatment of alcoholism, but does not link ALDH inhibition to its antifungal effect. The Results and Discussion (§3.1; page unavailable) instead proposes metal chelation and affinity for cysteine thiol groups as possible explanations for antifungal activity. Our copy does not identify urease or carbamate kinase as targets. (LLM, conf=0.88)

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References 61 · Cited by 2

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Authors
Lajarin-Reinares, M., Naveira-Souto, I., Mallandrich, M., Suñer-Carbó, J., Llagostera Casas, M., Calvo, M. A., & Fernandez-Campos, F.
Affiliations
  • Universitat Autònoma de Barcelona (ES)
  • Reig Jofre (Spain) (ES)
  • Universitat de Barcelona (ES)
  • Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
  • Department of Genetics and Microbiology, Campus Microbiology Unit, Autonomous University of Barcelona, 08193 Bellaterra, Spain
  • Department of Animal Health and Anatomy, Faculty of Veterinary, Autonomous University of Barcelona, 08193 Bellaterra, Spain
  • R & D Department, Labiana Pharmaceuticals, 08757 Corbera Llobregat, Spain
Corresponding author
Lajarin-Reinares, Maria
ORCID
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2023-05-08
Volume
15
Issue
5
Pages
1436
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics15051436
PMC
PMC10223105
OpenAlex
W4378516872
Cited by
2
References
61
Citations by year
2026: 2
FWCI
0.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Generalitat of Catalonia, Industrial Doctorate Program (2020 DI 97)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
disulfiram, vaginal candidiasis, mucoadhesive gel, vaginal drug delivery, antifungal activity, Candida albicans, Candida parapsilosis, Candida glabrata, polyethylene glycol, carrageenan, drug release, drug repurposing

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