Bioreducible Layer-By-Layer Films for Sequential Release of DNA

This presentation describes the use of polyelectrolyte films as sequential DNA delivery systems. Polycationic Reducible Hyper Branched Polymer (RHB) and polyanionic GFP DNA self-assemble into layer-by-layer films when dipped sequentially. The films deposit on surfaces of implants of varied type and shapes and are stable in non-reducible physiologic environment. We hypothesize that the films are capable of sequential release of DNA upon contact with cells with reducible proteins and in other reducible physiologic conditions. We have carried out experiments to improve cell adhesion, sequential release of DNA, and DNA transfection. We have found that cell adhesion to the films is improved by crosslinking of the films and by a surface coating of adhesion protein fibronectin. Films of RHB/DNA multilayers display bulk erosion behavior. We have changed this behavior to gradual film degradation and slow DNA release by inserting a non-reducible polycation in between RHB layers. This study offers a method to sequentially release DNA over a long period of time and may be applicable to tissue regeneration, cancer vaccine delivery, and stem cell research.