On demand release of anti-inflammatory drug or neurotropic factors have great promise for maintaining a stable chronic neural interface. Here we report the development of an electrically controlled drug release system based on conducting polymer and carbon nanotubes. Drug delivery research using carbon nanotubes (CNTs) has taken advantage of the ability of CNTs to load large amounts of drug molecules on their outer surface. However, the utility of the inner cavity of CNTs, which can increase the drug loading capacity, has not yet been explored. In this paper, the use of multi-wall CNTs as nanoreserviors for drug loading and controlled release is demonstrated. The CNTs are pretreated with acid sonication to open their ends and make their outer and inner surfaces more hydrophilic. When dispersed and sonicated in a solution containing the anti-inflammatory drug dexamethasone, experiments show that the pretreated CNTs are filled with the drug solution. To prevent the unwanted release of the drug, the open ends of the drug-filled CNTs are then sealed with polypyrrole (PPy) films formed through electropolymerization. The prepared electrode coating significantly reduced the electrode impedance, which is desired for neural recording and stimulation. More importantly, the coating can effectively store drug molecules and release the bioactive drug in a controlled manner using electrical stimulation. The dexamethasone released from the PPy/CNT film was able to reduce lipopolysaccharide induced microglia activation to the same degree as the added dexamethasone.

Neural electrodes hold tremendous potential for improving understanding of brain function and restoring lost neurological functions. Multi-walled carbon nanotube (MWCNT) and dexamethasone (Dex)-doped poly(3,4-ethylenedioxythiophene) (PEDOT) coatings have shown promise to improve chronic neural electrode performance. Here, we employ electrochemical techniques to characterize the coating in vivo. Coated and uncoated electrode arrays were implanted into rat visual cortex and subjected to daily cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) for 11 days. Coated electrodes experienced a significant decrease in 1 kHz impedance within the first two days of implantation followed by an increase between days 4 and 7. Equivalent circuit analysis showed that the impedance increase is the result of surface capacitance reduction, likely due to protein and cellular processes encapsulating the porous coating. Coating’s charge storage capacity remained consistently higher than uncoated electrodes, demonstrating its in vivo electrochemical stability. To decouple the PEDOT/MWCNT material property changes from the tissue response, in vitro characterization was conducted by soaking the coated electrodes in PBS for 11 days. Some coated electrodes exhibited steady impedance while others exhibiting large increases associated with large decreases in charge storage capacity suggesting delamination in PBS. This was not observed in vivo, as scanning electron microscopy of explants verified the integrity of the coating with no sign of delamination or cracking. Despite the impedance increase, coated electrodes successfully recorded neural activity throughout the implantation period.

This chapter explores the variability and limitations of traditional stimulation electrodes by first appreciating how electrical potential differences lead to efficacious activation of nearby neurons and examining the basic electrochemical mechanisms of charge transfer at an electrode/electrolyte interface. It then covers the advantages and current challenges of emerging micro-/nanostructured electrode materials for next-generation neural stimulation microelectrodes. Introduction to Electrical Stimulation of NeuronsStimulation electrodes have many clinical applications. The most common clinically approved stimulator is the artificial cardiac pacemaker, which is implanted into patients with a slow or arrhythmic heartbeat [1]. Artificial pacemakers use electrodes placed directly in contact with the heart muscles to regulate heart rate by delivering a timed series of electrical pulses. Another common stimulation device implanted into many adults and children is the cochlear implant [2]. Cochlear duct electrodes are designed as a series of stimulation contacts arranged along a flexible silicone carrier (Fig. 4.1a). These electrodes are placed into the cochlea where they directly electrically stimulate nerve cells, bypassing damaged hair cells that transduce acoustic vibrations into electrical impulses in the underlying nerve cells. (Fig. 4.1b). Electrical stimulation in these deep brain structures, such as the basal ganglia, has been used to treat symptoms of Parkinson's disease including tremor and bradykinesia, as well as other movement disorders such as dystonia [3][4][5]. In addition, DBS is being studied as a treatment for stroke, chronic pain, major depression, and chronic obesity [6-10]. For epilepsy and major depression, vagal nerve stimulation offers an alternative that does not require brain surgery [11,12]. In the extremities, functional electrical stimulation (FES) is used to deliver electrical current to activate nerves or muscles in disabled patients. FES has been applied to aid in standing, walking, and basic handgrips and for restoring bowel and bladder function [13][14][15]. Many other electrical stimulation applications exist, including the restoration of somatosensation and vision, the treatment of hypertension and gastroparesis, and the promotion of nerve regeneration [16][17][18][19].While these neurostimulation devices have demonstrated some success in bypassing, replacing, or treating damaged neural circuits, they are far from being able to reliably restore natural function in all patients. In order to understand the variability and limitations of traditional stimulation electrodes, we must first appreciate how electrical potential differences lead to efficacious activation of nearby neurons and examine the basic electrochemical mechanisms of charge transfer at an electrode/electrolyte interface. This chapter will first lay out our current knowledge of these areas and afterwards will cover the advantages and current challenges of emerging micro-/nanostructured electrode materials for ...