(618b) Drug Delivery From Neural Prostheses Using Polymer Composites

Neural prostheses restore lost function to patients with catastrophic nerve damage, congenital conditions, and degenerative neural disease. Existing devices have been very successful in the clinic, but development of advanced prostheses with large numbers of densely packed small electrodes has been hampered by biocompatibility limitations. Foremost among these appears to be the formation of a dense fibrotic scar surrounding the implant site. It is believed that this scar results in part from surgical trauma, but also from inherent chemical and mechanical material incompatibilities with the brain and nervous system. Our research is focused on applying concepts from tissue engineering to improve compatibility at this interface, minimizing scar formation, and hopefully improving the interface between devices and target tissue. It is anticipated that these effects will reduce electrical requirements for device operation permitting the use of small, densely packed electrode arrays that will enhance device resolution.

Our initial efforts in this area focused on the development of poly (ethylene glycol)-poly (lactic acid) (PEGPLA) polymer hydrogels to promote long-term release of neurotrophins to the retina. Neurotrophins (e.g., brain-derived neurotrophic factor) have been shown to enhance neuron survival and to promote extension of neuron processes. Additionally, PEG has been shown to greatly enhance the biocompatibility of implanted devices by resisting protein adsorption. We found that PEGPLA hydrogels can release neurotrophin for up to three weeks, and promote neurite extension in PC12 cell and retinal explant tissue culture models.

Because anticipated duration of the immune response is ~ 6-8 weeks, additional research efforts have focused on extending the release time of PEGPLA polymers by forming composites with other materials. We have investigated two composite systems. The first consists of biodegradable PEGPLA polymers complexed with PEG-diacrylates (PEGDA) to form PEGPLA-PEGDA hydrogels. It was anticipated that using PEGDAs of lower molecular weight than that of PEGPLA would shrink pore size therefore slowing release rate. In actuality, release rates were accelerated and overall release diminished by the addition of PEGDA, possibly because of the reduced degradability of the polymer which limits degradational release.

The second composite system that we investigated consisted of poly (lactic-co-glycolic acid) (PLGA) microspheres embedded in PEGPLA hydrogels. PLGA-PEGPLA composites have been investigated for similar applications previously by Langer's group (Burdick et al, Biomaterials, 27, 2006, 452) and exhibited release rates of 6-8 weeks, our target range. We have created similar composites and characterized their drug release and compatibility in cell culture.

Composite systems such as those described here provide methods to tune drug release and duration to particular applications. We anticipate that the application of these systems to neural prostheses will greatly improve their biocompatibility and function, permitting development of the next generation of devices.