Antibiofilm Therapies for the Treatment of Combat-Associated Infections
Abstract
Approved for Public ReleaseMilitary wound infections can be extremely debilitating and a significant cause of mortality.Biofilms are, frequently found at these wound infection sites and exacerbate the difficulty oftreating these infections. Two of the most prevalen,t bacteria found in these military woundinfections are methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonasaeruginosa,, which are common biofilm forming bacteria. We have found that biofilm bacteriacan be effectively treated with combinations of Food,and Drug Administration approvedantibiotics and a range of compounds that exhibit antibiofilm behavior. Additionally, we havedevelop,ed polymeric nanoparticles that can penetrate and respond to the biofilmmicroenvironment to trigger the release of encapsulated ther,apeutics. In this work, we propose toinvestigate the antibiofilm efficacy of various combination therapies against MRSA and P.aerugi,nosa in vitro. We will identify therapeutic combinations that exhibit synergisticmechanisms of action and explore the effect of intr,oducing time delays between therapeutictreatments on biofilm viability. Promising combinations will be encapsulated in responsivepol,ymer nanoparticles, and properties of these nanoparticles, including size and therapeuticloading and release behavior, will be quant,ified. The ability of these nanoparticles to eradicateMRSA and P. aeruginosa biofilms will be investigated in vitro. Finally, a muri,ne biofilmexcisional wound infection model will be established for MRSA and P. aeruginosa. Promisingcombination therapies and nanopa,rticle therapies will be examined for their infection eradicationability in this in vivo model. This work has the potential to lead,to the discovery of promisingnew approaches to eradicate biofilm infections, which can significantly improve outcomes forwounded ind,ividuals. The proposed scope of work is Fundamental Research, and thetechnologies developed through this proposal will be applicable, to both military and civilianapplications.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 16, 2022
- Source ID
- N000142212336
Entities
People
- Anita Shukla
Organizations
- Brown University
- Office of Naval Research
- United States Navy