Novel, bio-inspired chloramine to treat cutaneous fungal infections without resistance generation potential

PROJECT SUMMARY Resistance due to mutations in fungi is a result of widespread use of antifungals, which has led to an increase in chronic cases, and is considered an increasing public health burden by the CDC. The CDC recently flagged antifungal resistance as an increasing threat in the US, particularly with respect to ringworm. Halomine, doing business as AvantGuard, has developed a stabilized chloramine that creates a novel active with residual efficacy to serve as an antifungal, providing excellent broad-spectrum efficacy and no history of resistance generation. Our polymer is a combination of an N-halamine containing monomer and other monomers that improve solubility. Key differentiators are: Chlorine is broad spectrum; the molecules are too large for uptake by cells, reducing cell death; no resistance generation; the formulation has shown no skin irritability; chlorine is a quick and efficient antimicrobial. The proposal is designed to optimize the product against fungi that cause tinea (ringworm): 1) Test the MIC/MBC for a larger cohort of fungi, followed by incorporation into a hydrogel format to confirm the broad-efficacy of the compound. 2) The resulting formulations will be examined for ability to reduce biofilms in vivo in a porcine model against T. rubrum or T. interdigitale. These results will be compared to efficacy of miconazole (Miconazole 7 – 2%, TopCare), clotrimazole (Clotrimazole cream - USP 1%, TopCare), and an untreated control group, with a milestone of improved performance against the competition. 3) The formulations will undergo safety testing via an Acute Dermal Irritation procedure following OCSPP 870.2500/OECD 404 guidance.