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(17h) Multilayered Polymer Thin Films for Sequential Delivery of Multiple Agents

Hammond, P. T., Massachusetts Institute of Technology

Multilayered polymer thin films have been constructed via the layer-by-layer (LbL) deposition technique, in which polycations and polyanions are alternately deposited onto a substrate. The LbL fabrication process results in ultrathin films that are highly conformal and can be applied to virtually any surface material with no restriction on size or geometry. Furthermore, the process only involves aqueous solutions at mild pH, rendering it cheap, simple, and safe towards sensitive biologic drugs. Using a unique water-hydrolyzable polycation, we have constructed coatings that are stable in air but erode top-down controllably in an aqueous physiological environment. By encapsulating agents within different layers of these stratified coatings, a single polymer thin film can elute multiple drugs sequentially, with individually tunable dosage and timing. Preliminary studies have shown the sequential release of multiple distinct polysaccharides. We have fabricated antimicrobial and anticoagulant films with controls over the release rate and dosage through appropriate choices in film architecture and constituent polymer properties. In vitro assays have demonstrated the efficacy of these films in inhibiting S. aureus growth, in the case of the antibiotic-loaded film, or in increasing proliferation of a heparin-responsive murine cell line, in the case of the anticoagulant-loaded film. Other coatings currently under study in our group involve anti-inflammatories, growth factors, and additional classes of antibiotics. A potential application of this technology is orthopedic implant coatings that can address multiple complications of pain, infection, and implant rejection through the sequential releases of pain killers, antibiotics, and growth factors. Aside from drug-eluting coatings on biomedical devices, this technology can also be applied towards the delivery of a single therapeutic agent with a complex release profile, such as a self-scheduling vaccine.