Novel Cyclic Lipopeptides for Treating Complicated Wound Infections
Technical Report,21 Sep 2017,20 Sep 2018
University of Miami Miller School of Medicine MIAMI United States
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The purpose for this grant is to develop a new class of antibacterial agents, cyclic lipopeptides, derived from the fusaricidinLI-F family of naturally occurring antifungal antibiotics for the prevention and treatment of complicated combat-related or trauma-induced wound infections caused by multidrug-resistant MDR pathogens and biofilm formation. Three aims are planned 1 To optimizesynthesize lead cyclic lipopeptides and assess their antimicrobialantibiofilm activity and toxicity in vitro 2 to develop and optimize a cyclic lipopeptide delivery system based on anionic graft copolymer nanoparticles for topical application and 3 to characterizeoptimize, evaluate dosing, efficacy, and toxicitysafety of the combined cyclic lipopeptidepolymer nanocomplexes in several porcine models for infection prevention, biofilm elimination, and wound healing. The modification of the amino acid sequences of lead depsipeptides will disrupt the balance between the charge and hydrophobicity leading to a better separation of antibacterial activity and nonselective toxicity. In vitro and in vivo studies will be performed to study antimicrobial and wound healing efficacy.
- Medicine and Medical Research