Controlling complexation between anionic gels and cationic antimicrobials

Self-defensive surfaces that resist bacterial colonization have been increasingly studied over the past decade. We have explored such surfaces using microgels of polyacrylic acid (PAA). They are electrostatically deposited onto a surface and loaded by complexation with cationic antimicrobial peptides. We have shown that contact with bacteria can trigger the release of the antimicrobial, which then kills the challenging bacterium. A key issue in this approach is to ensure stable microgel-antimicrobial complexation under physiological conditions. Colistin, an FDA-approved antibiotic with five positive charges, can be sequestered in PAA microgels in low ionic strength phosphate buffer but is quickly released when exposed to phosphate buffered saline (PBS) with higher ionic strength. We have studied various microgel-antimicrobial combinations to better understand what physicochemical properties most influence the complexation strength. We study this by in situ imaging to establish critical salt concentrations required for release as well as by coarse-grained modeling. In addition to the total net electrostatic charge, we have found, that aromaticity in the microgel (e.g. polystyrene sulfonate) or in the antimicrobial (e.g. polymyxin B) enhances the complexation strength. Our most recent work concentrates on antimicrobials that self-assemble in solution to form bundles and other supramolecular structures, which bring higher net charges and charge densities to the complexation process.