Nanoparticle-based drug delivery systems for neural interfaces - a novel approach for improved biocompatibility.

The overall purpose of this thesis was to reduce brain tissue responses around implanted microelectrodes using a pharmacological strategy. One of the main aims was to develop and evaluate drug delivery systems that allow local administration of anti-inflammatory pharmaceutics. The drug Minocycline was therefore encapsulated into biodegradable poly (D,L-lactic-co-glycolic acid) nanoparticles and thereby also protecting the drug from degradation. The nanoparticle construct resulted in a sustained release of Minocycline over 30 days. This constitutes a substantial increase in release time compared to what has until now been achieved for the drug. The drug-loaded nanoparticles were then embedded in a fast-dissolving gelatin coating surrounding the implant which enabled local and sustained drug release at the target site. This technique supersedes any of the conventional administration routes and minimizes the risk for systemic side effects. The developed drug delivery system was found to significantly attenuate the acute brain tissue responses around implanted microelectrodes in mice. Coatings with Minocycline-loaded nanoparticles significantly reduced the activation of microglia cells compared to control coatings with gelatin alone both 3 and 7 days post implantation. This without affecting the overall microglia population. A significant reduction of the astrocytic response was also found 7 days post implantation in comparison to control implants. No effect on neurons or total cell count was found which may suggest that the Minocycline-loaded nanoparticles are non-toxic to the central nervous system. The thesis also presents a novel nanoparticle-eluting compartmentalized microelectrode that transforms into a flexible tube once implanted.