There is an urgent need to develop new therapeutic strategies to treat bacterial skin infections. Current treatment regimens based on antibiotics are being hindered by the growing number of drug -resistant bacterial strains. Millions of people worldwide are affected by drug -resistant bacteria and associated economic costs are in excess of 10 billion dollars annually. To address this issue, we have taken inspiration from the human body’s innate immune system. Antimicrobial lipids (AMLs) are naturally found on the skin surface and display broad-spectrum antimicrobial activity, including against the methicillin -resistant Staphylococcus aureus (MRSA) strain. A key technical challenge is developing aqueous formulations of AMLs with high loading efficiencies for topical skin applications. Herein, our main hypothesis is that peptide amphiphile (PA) nanofibers can provide a suitable environment to deliver AMLs to bacterial targets. The proposed nanofiber-based strategy represents a nanoscale platform technology to incorporate multiple types of AMLs, each preferentially targeting a specific subset of bacterial strains to collectively produce broad-spectrum antibacterial activity. In total, the proposed work will combine engineering characterization of nanofiber-AML formulations with in vitro bacterial tests and an in vivo mouse ear model in order to establish a broad-spectrum antibacterial skin therapy ready for human clinical testing. Indeed, the broad-spectrum antibacterial agents are composed entirely of natural products that are FDA-approved and the proposed formulations are compatible with GMP production. Compared to existing antibiotic treatment strategies, additional competitive advantages include broad-spectrum activity with low cytotoxicity and capability to inhibit drug-resistant bacterial strains.
|Effective start/end date||11/1/14 → 10/31/19|
- Nanyang Technological University (Agmt 10/20/14)
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