Controlling the surface-mediated release of DNA using 'mixed multilayers'

We report the design of erodible 'mixed multilayer' coatings fabricated using plasmid DNA and combinations of both hydrolytically degradable and charge-shifting cationic polymer building blocks. Films fabricated layer-by-layer using combinations of a model poly(β-amino ester) (polymer 1) and a model charge-shifting polymer (polymer 2) exhibited DNA release profiles that were substantially different than those assembled using DNA and either polymer 1 or polymer 2 alone. In addition, the order in which layers of these two cationic polymers were deposited during assembly had a profound impact on DNA release profiles when these materials were incubated in physiological buffer. Mixed multilayers ∼225 nm thick fabricated by depositing layers of polymer 1/DNA onto films composed of polymer 2/DNA released DNA into solution over ∼60 days, with multi-phase release profiles intermediate to and exhibiting some general features of polymer 1/DNA or polymer 2/DNA films (e.g., a period of rapid release, followed by a more extended phase). In sharp contrast, 'inverted' mixed multilayers fabricated by depositing layers of polymer 2/DNA onto films composed of polymer 1/DNA exhibited release profiles that were almost completely linear over ∼60-80 days. These and other results are consistent with substantial interdiffusion and commingling (or mixing) among the individual components of these compound materials. Our results reveal this mixing to lead to new, unanticipated, and useful release profiles and provide guidance for the design of polymer-based coatings for the local, surface-mediated delivery of DNA from the surfaces of topologically complex interventional devices, such as intravascular stents, with predictable long-term release profiles.