University of Kentucky
Preparation of Devices for Release of Antimicrobial Peptides
Institution
University of Kentucky
Faculty Advisor/ Mentor
David Puleo; Karen Novak
Abstract
Bacteria and bacterially derived products stimulate inflammation and lead to the destruction of structural tissues in conditions such as periodontitis and peri-implantitis. To enable tissue regeneration, the first step is to eliminate the microbial burden. In this project, the polymer blend system of cellulose acetate phthalate (CAP) and Pluronic F127 is being explored for use in killing bacteria. Intrinsic antimicrobial activity of the polymer is being assessed first, followed by its use for controlled release of antimicrobial peptides. Drug-loaded CAP-Pluronic microspheres were made by a water-acetone-oilwater triple emulsion process. Release devices were made by alternately layering and pressure-sintering microspheres to enable modulation of the drug concentration profiles. Six-layer devices gave three peaks of increased peptide concentration. Under simulated physiological conditions, the total duration of release was nine to eleven days. Intermittent release of peptide was achieved. The release profiles can be controlled by varying polymer layers, coating method, and release conditions. Initial bioactivity studies used E. coli as a test bacterium for determining antibacterial effects of the polymer and peptide. CAP-Pluronic alone resulted in a concentration-dependent inhibition of bacterial growth, indicating it has intrinsic bacteriostatic properties. In conjunction with the antimicrobial peptide WLBU2, the number of viable bacteria was further reduced, although complete killing has not yet been achieved. Ongoing experiments are focused on enhancing the bactericidal activity against additional species of bacteria, including those responsible for gum diseases, such as periodontitis and periimplantitis.
Preparation of Devices for Release of Antimicrobial Peptides
Bacteria and bacterially derived products stimulate inflammation and lead to the destruction of structural tissues in conditions such as periodontitis and peri-implantitis. To enable tissue regeneration, the first step is to eliminate the microbial burden. In this project, the polymer blend system of cellulose acetate phthalate (CAP) and Pluronic F127 is being explored for use in killing bacteria. Intrinsic antimicrobial activity of the polymer is being assessed first, followed by its use for controlled release of antimicrobial peptides. Drug-loaded CAP-Pluronic microspheres were made by a water-acetone-oilwater triple emulsion process. Release devices were made by alternately layering and pressure-sintering microspheres to enable modulation of the drug concentration profiles. Six-layer devices gave three peaks of increased peptide concentration. Under simulated physiological conditions, the total duration of release was nine to eleven days. Intermittent release of peptide was achieved. The release profiles can be controlled by varying polymer layers, coating method, and release conditions. Initial bioactivity studies used E. coli as a test bacterium for determining antibacterial effects of the polymer and peptide. CAP-Pluronic alone resulted in a concentration-dependent inhibition of bacterial growth, indicating it has intrinsic bacteriostatic properties. In conjunction with the antimicrobial peptide WLBU2, the number of viable bacteria was further reduced, although complete killing has not yet been achieved. Ongoing experiments are focused on enhancing the bactericidal activity against additional species of bacteria, including those responsible for gum diseases, such as periodontitis and periimplantitis.