Engineering a Layer-by-Layer (LbL) Film for The Extended Release of Antibiotics and Modeling Drug Release Behavior
The current release system for orthopedic implants provides a significant level of antibiotic release over approximately two weeks in vitro; however, it would be desirable to achieve sustained release over a period of approximately six to eight weeks, providing sufficient antibiotic at long times to maintain localized concentrations above the MIC as new bone is generated at the interface of the implant. The primary goal of my work is to provide the first substantive models of electrostatically assembled thin films as controlled release systems, and inform the research with regard to control and predictive capabilities that guide design of gentamicin thin films, as well as understanding the best routes to extension of the release time. In conjunction with design principles revealed from modeling of these systems, new modes of gentamicin incorporation that involve the delayed release of increased loadings of gentamicin, including the encapsulation of gentamicin into charged degradable polymer nanoparticles that are assembled into the film, and the introduction of benign crosslinking chemistries will be investigated. Ultimately, we will generate combination antibiotic and growth factor films for controlled sequential release as a joint work. This will involve the use of intermediary barrier layers in the film to enable true sequential release of the different agents. Finally, release behavior of these films will be examined in animal models developed in previous work.