Programmable Biologic Drug Delivery using Electrostatic Polymer Assembly

By alternating positively and negatively charged molecules in sequence, it is possible to generate thin films one nano-layer at a time while controlling the composition of the film with great precision. This electrostatic layer-by-layer (LBL) process is a simple and elegant method of constructing highly tailored ultrathin polymer and organic-inorganic composite thin films. We have used this method to develop thin films that can encapsulate and release proteins and biologic drugs such as growth factors with highly preserved activity from the surfaces of biomedical implants or wound dressings with sustained release over periods of several days. We have engineered coatings that yield release of different drugs, DNA or protein, resulting in highly tunable multi-agent delivery nanolayered release systems for tissue engineering, biomedical devices, and wound healing applications. Finally, the manipulation of charge to target other tissues, in particular cartilage, is an important means of targeting the joint for osteoarthritis. We have generated unimolecular charged nanocarriers that can be precisely tuned to achieve deep penetration into avascular tissues such as cartilage to enable extended release treatments for cartilage regeneration. These and other uses of controlled polyelectrolytes and their complexes for delivery within tissues and across barriers will be addressed.