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Prevention and Treatment of Fungal Skin Infections Using Cationic Polymeric Films.

ABSTRACT: Dermatophytosis is a fungal infection of skin, nails and hair. Treatments can be long and infections are often recurrent, and novel treatments are desirable. Here we tested the use of polymeric films that can be sprayed on the skin for the prevention and treatment of dermatophytosis. The two polymers selected were ABIL T Quat 60 and Eudragit E100, which were tested ex vivo using a porcine skin model, and in vitro using microbiological and microscopy techniques. Acceptability of the polymeric films was tested on the skin of healthy volunteers. The results showed that ABIL and Eudragit films prevented and treated fungal skin infections. Whilst polymer films may provide a physical barrier that prevents fungal colonization, it was shown that both polymers are active antifungals ex vivo and in vitro and have intrinsic antifungal activity. For ABIL, we also established that this polymer binds essential nutrients such as metal ions and sugars, thereby restricting the growth of fungi. When applied to healthy subjects' skin, the polymeric films neither modified the skin color nor increased trans-epidermal water loss, suggesting a low potential for skin irritation, and the approach was generally found to be acceptable for use by the volunteers. In conclusion, we developed a novel strategy for the potential prevention and treatment of dermatophytosis.

SUBMITTER: Ho FK

PROVIDER: S-EPMC8398677 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Most skin infections, including those complicating burns, are polymicrobial involving multiple causative bacteria. Add to this the fact that many of these organisms may be antibiotic-resistant, and a simple skin lesion or burn could soon become life-threatening. Membrane-acting cationic peptides from Gram-negative bacteriophage lysins can potentially aid in addressing the urgent need for alternative therapeutics. Such peptides natively constitute an amphipathic region within the structural composition of these lysins and function to permit outer membrane permeabilization in Gram-negative bacteria when added externally. This consequently allows the lysin to access and degrade the peptidoglycan substrate, resulting in rapid hypotonic lysis and bacterial death. When separated from the lysin, some of these cationic peptides kill sensitive bacteria more effectively than the native molecule via both outer and cytoplasmic membrane disruption. In this study, we evaluated the antibacterial properties of a modified cationic peptide from the broad-acting lysin PlyPa01. The peptide, termed PaP1, exhibited potent in vitro bactericidal activity toward numerous high priority Gram-positive and Gram-negative pathogens, including all the antibiotic-resistant ESKAPE pathogens. Both planktonic and biofilm-state bacteria were sensitive to the peptide, and results from time-kill assays revealed PaP1 kills bacteria on contact. The peptide was bactericidal over a wide temperature and pH range and could withstand autoclaving without loss of activity. However, high salt concentrations and complex matrices were found to be largely inhibitory, limiting its use to topical applications. Importantly, unlike other membrane-acting antimicrobials, PaP1 lacked cytotoxicity toward human cells. Results from a murine burn wound infection model using methicillin-resistant Staphylococcus aureus or multidrug-resistant Pseudomonas aeruginosa validated the in vivo antibacterial efficacy of PaP1. In these studies, the peptide enhanced the potency of topical antibiotics used clinically for treating chronic wound infections. Despite the necessity for additional preclinical drug development, the collective data from our study support PaP1 as a potential broad-spectrum monotherapy or adjunctive therapy for the topical treatment of polymicrobial infections and provide a foundation for engineering future lysin-derived peptides with improved antibacterial properties.

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Prevention and Treatment of Fungal Skin Infections Using Cationic Polymeric Films.

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