| Autor: |
Lajarin-Reinares M; Topical & Oral Development, Research and Development Reig Jofre Laboratories, 08970 Barcelona, Spain.; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain., Pena-Rodríguez E; Topical & Oral Development, Research and Development Reig Jofre Laboratories, 08970 Barcelona, Spain., Cañellas-Santos M; Biotechnology Department, Research and Development Reig Jofre Laboratories, 08970 Barcelona, Spain., Rosell-Vives E; Biotechnology Department, Research and Development Reig Jofre Laboratories, 08970 Barcelona, Spain., Cortés P; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain., Casas ML; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain., Calvo MÀ; Department of Animal Health and Anatomy, Faculty of Veterinary, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain., Fernandez-Campos F; Topical & Oral Development, Research and Development Reig Jofre Laboratories, 08970 Barcelona, Spain. |
| Abstrakt: |
Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes . Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections. |
