摘要：

Invasive fungal infections have high mortality rates, and many current antimycotics are limited by host toxicity and drug resistance. Recent experiments in our laboratory have demonstrated the antifungal activity of dKn2-7, a synthetic peptide, against Candida albicans. The purpose of the current study was to develop a wound dressing capable of dKn2-7 release for extended periods to help combat fungal infection in wounds. dKn2-7 was incorporated into calcium alginate microfibers, an excipient with known wound healing and hemostatic properties. dKn2-7 release rates from the fibers were dependent on drug loading, but all formulations exhibited a burst release with 41-71 % of total theoretical release in the first 15 min and 84-96 % release by 24 h. Calcium release at 15 min was similar to that of a commercial hemostatic dressing, indicating dKn2-7 loading would not adversely affect the hemostatic capability of the alginate fibers. In vitro antifungal studies indicated a dose dependent effect with fibers loaded at ≥20 µg/mg causing significant planktonic killing and ≥30 µg/mg causing significant biofilm killing. Viable fungal counts in biofilms grown on ex vivo porcine skin declined by 99 % following 500 µg/mg fiber treatment. Skin histology indicated no significant differences in tissue damage between treatment groups and controls. Results confirm calcium alginate microfibers are capable of binding and subsequently releasing dKn2-7 over a 24-h period when rehydrated. Furthermore, dKn2-7 released from the fibers was able to significantly reduce biofilms in an ex vivo model with minimal toxicity, indicating these dKn2-7-loaded fiber dressings may be effective at controlling C. albicans biofilm infections in vivo.

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