609d Nanoporous Drug Delivery Devices Based on Functional Polymers

Hongyan He, Chi Yen, Shengnian Wang, Chee Guan Koh, Yong Yang, W. S. Winston Ho, and L. James Lee. Ohio State University, 140 west 19th. Ave., Columbus, OH 43210

Many protein- and DNA-based drugs exhibit high sensitivity to the surrounding physiological conditions as a result of their delicate physicochemical characteristics. They need to be properly protected during administration and their release needs to be precisely targeted and controlled. A major limitation of these available delivery devices is that they cannot fully protect the drugs and release them at a controllable rate over a long period of time. To develop a robust manufacturing protocol, a number of micro- and nano-manufacturing modules have been integrated to produce particulate-like polymer nanoporous devices that consists of two parts: a drug reservoir and a nanoporous membrane/nanonozzle gate. Porous membranes composed of the biodegradable polyesters were prepared by a phase inversion process. The pore size and membrane structure were controlled by polymer composition and evaporation time. The sacrificial template nano-imprinting was applied for the nanonozzle preparation. The nanostructures were characterized by a series of analytical tools: scanning electron microscopy (SEM), atomic force microscopy (AFM), and optical surface profilometry. Mechanical properties, biocompatibility, and biodegradation of devices constructed from biodegradable polymers were determined experimentally. The release of bioactive compounds (lysozyme and interferon-a) was evaluated in a Costar Transwell Test Setup. Such devices are likely to enhance the bioavailability of existing therapeutic such as protein and nucleic acid drugs, and provide a continuous, pre-designed release profile within the local tumor environment, potentially without the need for surgical implantation.