(99a) Preventing Bacterial Colonization of Surfaces with Layer-By-Layer Coatings of Fluorinated Polyphosphazenes and Antibiotics

Preventing bacterial colonization of biomedical surfaces, ranging from skin grafts to hip implants, is highly desirable. Such a goal can be achieved by coating materials with biocompatible, polymeric layers that release antibiotics in response to a trigger that occurs at the onset of infection, such as locally induced acidification. Here, we explore pH-responsive coatings constructed with ionic fluorinated polyphosphazenes (PPzs). PPzs are promising building blocks for biomaterials due their known biocompatibility and unique structure of the repeat unit, which enables control over charge density and hydrophobicity as well as over the biodegradation rate. Traditional polyelectrolytes are unable to directly form coatings with cationic antibiotics at neutral pH and suffer from high degrees of antibiotic release upon exposure to physiological concentrations of salt. In contrast, fluorinated PPzs enabled unique, not possible with common polyelectrolytes, direct layer-by-layer assembly with cationic antibiotics, such as polymyxin B, colistin, gentamicin, and neomycin. The amount of antibiotics bound in the coatings could be tuned by the degree of fluorination of PPzs and/or film thickness. The coatings were able to prevent the onset of bacterial growth of E. coli and S. aureus in solution via antibiotic release (with antibiotic doses highly tunable via PPz fluorination degree and/or film thickness) and were also highly surface active. Importantly, coatings remained highly surface active against E. coli and S. aureus even after 30 days of pre-exposure to bacteria-free physiological conditions or after repeated bacterial challenge. Moreover, coatings displayed low (<1%) hemolytic activity for both rabbit and porcine blood. Deposition of the coatings on either hard (Si wafer, Ti substrate) or soft (electrospun fiber matrices) materials resulted in materials which were non-toxic towards fibroblasts (NIH/3T3) and displayed controllable fibroblast adhesion via PPz fluorination degree. Taken together, these results suggest a new way to form highly tunable, biocompatible polymer coatings for medical device surfaces.