Antimicrobial Peptide Delivery from Degradable Polymer Thin Films

Abstract

The overuse of antibiotics has led to a rise in antibiotic resistance of common hospital dwelling bacteria such as Staphylococcus aureus. Novel broad-spectrum antimicrobials that operate without further contributing to a rise in antibiotic resistance are needed to tackle this problem. The effective delivery of antimicrobial peptides, is of interest due to their wide range of activity against gram positive and gram negative bacteria, as well as low onset of bacterial resistance. Our work focuses on using polyelectrolyte multilayer films for the delivery of these novel therapeutics targeting S. aureus infections. Such constructs could easily be implemented in localized delivery systems, applied directly to a wound site. We have examined hydrolytically degradable layer-by-layer constructed films for the delivery of an antimicrobial peptide, ponericin G1. This peptide exhibits a low S. aureus minimum inhibitory concentration, as well as low blood cell lysis. Poly(beta-amino esters), containing hydrolysable ester bonds, have been incorporated into multilayer films in order to controllably deliver functional doses of ponericin G1 over the desired release time scales. Current results show this technique to be highly effective in delivering functional ponericin over many days. The exact release profiles show a strong dependence on the polyanions used during film construction.