Controlled Release Films and Functional Surfaces Targeting Infection, Inflammation, and Bleeding

Medical conditions are often exacerbated by the onset of infection caused by hospital dwelling bacteria such as Staphylococcus aureus. Soldiers in particular are highly susceptible to such infections. Treatment typically includes prophylaxis with broad-spectrum antibiotics. Although this often provides a rapid cure for a potential infection, systemic toxicity of the therapeutics can not be avoided. The large and frequent drug doses used to target the infected site can eradicate the beneficial bacteria in our bodies, while allowing resistant bacteria to flourish, contributing to the rise in antibiotic resistant bacteria seen over the last several decades. An alternative that could alleviate systemic toxicity while maintaining effective local drug concentrations is needed. As a solution to this problem, we have examined degradable polymer thin films for use in localized delivery of both (1) existing and highly effective antibiotics and (2) novel therapeutics that do not cause antimicrobial resistant bacteria to arise. In both cases, the local delivery system would require much smaller drug doses, targeting only the infected site and eliminating systemic drug toxicity effects.

Work focuses on the use of polyelectrolyte multilayer films for the delivery of existing and highly effective antibiotics as well as antimicrobial peptides targeting Staphylococcus aureus. These films can coat a variety of surfaces for local delivery, including wound healing and implant materials. We have examined hydrolytically degradable layer-by-layer (LBL) assembled films, utilizing poly(β-aminoesters), for the delivery of a potent antibiotic, vancomycin hydrochloride as well as a natural antimicrobial peptide, ponericin G1. Vancomycin is often used as the first line of defense against many resistant gram-positive bacteria strains, while ponericin G1 is a broad-spectrum antimicrobial showing activity against gram-positive, gram-negative, and multi-drug resistant bacteria, with no indication of the development of resistance. Current results show the LbL technique to be highly effective for the delivery of these therapeutics over a range of hours to several days, with varying release profiles. The film released therapeutics retain activity against S. aureus. Drug loading and release is found to be highly dependent on film architecture, particularly the counter polyanion used in film construction, as well as the LbL assembly technique utilized, including aqueous dipped LBL and spray LBL assembly. Additionally, concurrent delivery with anti-inflammatories is also being examined for various therapeutic applications.

We have also recently begun work on the delivery of hemostatic agents from these degradable film constructs. Uncontrolled hemorrhage is the leading cause of death in the military and having an effective fast acting means of stopping bleeding is of critical importance.