Novel Cyclic Lipopeptides for Treating Complicated Wound Infections
Abstract
The purpose for this grant was to develop a new class of antibacterial agents, cyclic lipopeptides, derived from the fusaricidin/LI-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 were planned: (1) To optimize/synthesize lead cyclic lipopeptides and assess their antimicrobial/antibiofilm 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 characterize/optimize, evaluate dosing, efficacy, and toxicity/safety of the combined cyclic lipopeptide/polymer nanocomplexes in several porcine models for infection prevention, biofilm elimination, and wound healing. The modification of the amino acid sequences of lead depsipeptides were designed to 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 were performed to study antimicrobial and wound healing efficacy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1094827
Entities
People
- Stephen C. Davis
Organizations
- University of Miami