Cationic polymers that assemble reversibly with anionic polymers under physiological conditions are of interest for a broad range of biotechnical and pharmaceutical applications, including gene and drug delivery and the development of new polyelectrolyte-based surface coatings. We have designed a new class of “charge-shifting” cationic polymers that permit control over the assembly and disassembly of macromolecular aggregates and assemblies in aqueous environments. The conjugation of ester-functionalized side chains to cationic polymer backbones yields polymers that change charge states dynamically via side chain hydrolysis when exposed to physiological media. These changes in net charge and charge density result in changes in the nature of electrostatic interactions within polycation/polyanion complexes and assemblies. For example, we have demonstrated that charge-shifting cationic polymers based on the conjugate addition of methyl acrylate to linear poly(ethylenimine) promote the reversible assembly of these polymers with DNA in physiologically relevant media and enhance the delivery of DNA to cells.

This presentation will focus on the application of these charge shifting materials to the layer-by-layer assembly of ultrathin, erodible multilayered polyelectrolyte films (e.g., from 40 nm to 100 nm thick) using model anionic polymers or plasmid DNA. These ultrathin films erode and release DNA when incubated in phosphate-buffered saline (PBS) at rates dependent on polymer structure, and we demonstrate that the DNA released from these films remains transcriptionally active and able to promote transgene expression in mammalian cells. We demonstrate further that these charge-shifting cationic polymers can be used to fabricate ultrathin films that erode in a controlled manner and permit the design of films that can be used to release two types of DNA sequentially (i.e., rapid release of a first type of DNA followed by slower release of a second DNA construct) and that the order in which these two DNA constructs are released can be dictated by the order in which they are deposited during film fabrication. The application of these erodible films to the promotion of surface-mediated delivery of DNA to cells will be discussed.