(197m) Formulation of Peptide Antimicrobials for Treatment of Wound Infections
Poly(alkylacrylic acid) polymers were prepared via free radical polymerization under N2 using azobisisobutyronitrile as the initiator. Next, grafted copolymers were prepared by attaching polyetheramine chains to the poly(alkylacrylaic acid) backbones through carbodiimide coupling. All polymers were characterized by NMR and GPC and tested for their ability to form sub-micron particles encapsulating CAMPs that include well established CAMPs such as KSL-W and polymyxin B as well as novel cyclic lipopeptide provided by a collaborator. In contrast to our previous work using these polymers to coat lipoplexes for oligonucleotide delivery, here graft copolymers with poly(methacrylic acid) backbones proved more effective than those built on poly(propylacrylic acid) in encapsulation of peptides and forming stable nano-sized complexes. These complexes are to protect KSL-W, from degradation in human plasma for up to 24 hours while maintaining the free peptideâs activity against the gram-positive bacteria, S. aureus. By varying the graft percentage in the range of 0-10%, we are able to tune the release rate of polymyxin B from 1-10 days. Furthermore, the nanocomplexes were active against Klebsiella pnemoniae biofilms, with additive activity resulting from the polymer and the peptide in the nanocomplex.
Together, these results indicate that our graft copolymer formulation is effective at protecting, releasing and potentiating the activity of CAMPs. Future work will explore the formulation of these nanocomplexes within gels for topical administration.