(4cy) Controlled Release Films and Functional Surfaces for Applications in Medicine

The field of drug delivery is plagued by the lack of effective local delivery methods for multiple therapeutics over medically relevant timescales. Such capabilities are needed to treat cellular dysfunction while avoiding drug toxicity. A clear illustration of this problem is the systemic overuse of broad-spectrum antibiotics to treat bacterial infections, which has lead to a rise in antibiotic resistant bacteria worldwide. As an alternative to conventional systemic administration of therapeutics, we have designed layer-by-layer assembled degradable polyelectrolyte multilayer films as coatings to address infection. These films were engineered for the delivery of both existing and highly effective antibiotics as well as antimicrobial peptides, a novel class of therapeutics that do not cause antimicrobial resistant bacteria to arise. Film architecture, assembly technique, and film component secondary interactions were thoroughly explored and optimized to create active films which display a range of drug release profiles. These timescales and drug loadings are relevant to a wide range of medical needs, including those in which immediate eradication of an existing infection are required versus prophylactic administration. Recognizing the prevalence of infection and inflammation coexistence, degradable coatings for the concurrent release of antibiotics and anti-inflammatory therapeutics were also designed. All coatings were applied to medically relevant substrates, including bandages and sutures, and shown to be active in vitro. Additionally, to address the growing problem of biofilm formation on the surfaces of implants, non-degradable coatings were designed and shown to be highly effective in preventing bacterial attachment, the first critical step in biofilm formation. Together, these functionalized surfaces and drug releasing films have the potential to eliminate many of the current complications in treatment and prevention of infection.