Electrically Controlled Neurochemical Delivery from Microelectrodes for Focal and Transient Modulation of Cellular Behavior

Abstract

Electrically controlled drug delivery of neurochemicals and biomolecules from conducting polymer microelectrode coatings hold great potentials in dissecting neural circuit or treating neurological disorders with high spatial and temporal resolution. The direct doping of a drug into a conducting polymer often results in low loading capacity, and the type of molecule that can be released is limited. Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with sulfonated silica nanoparticles (SNP) has been developed as a more versatile platform for drug delivery. In this work, we demonstrate that neurochemicals with different surface charge, e.g., glutamate (GLU), gamma-Aminobutyric acid (GABA), dopamine (DA), 6,7-Dinitroquinoxaline- 2,3-dione (DNQX) and bicuculline, can be, respectively, incorporated into the SNP and electrically triggered to release repeatedly. The drug loaded SNPs were incorporated in PEDOT via electrochemical deposition on platinum microelectrodes. After PEDOT/SNP(drug) coating, the charge storage capacity (CSC) increased 10-fold to 55 ± 3 mC/cm2, and the impedance at 1 kHz was also reduced approximately 6-fold. With the aid of a porous SNP, the loading capacity and number of releases of GLU was increased >4-fold and 66-fold, respectively, in comparison to the direct doping of PEDOT with GLU (PEDOT/GLU). The focal release of GLU and GABA from a PEDOT/SNP (drug) coated microelectrode were tested in cultured neurons using Ca imaging. The change in fluo-4 fluorescence intensity after electrically triggered GLU (+6.7 ± 2.9%) or GABA (−6.8 ± 1.6%) release indicated the successful modulation of neural activities by neurotransmitter release. In addition to activating neural activities, glutamate can also act on endothelial cells to stimulate nitric oxide (NO) release. A dual functional device with two adjacent sensing and releasing electrodes was constructed and we tested this mechanism in endothelial cell cultures. In endothelial cells, approximately 7.6 ± 0.6 nM NO was detected in the vicinity of the NO sensor within 6.2 ± 0.5 s of GLU release. The rise time of NO signal, T0–100, was 14.5 ± 2.2 s. In summary, our work has demonstrated (1) a platform that is capable of loading and releasing drugs with different charges; (2) proof of concept demonstrations of how focal release of drugs can be used as a pharmacological manipulation to study neural circuitry or NO’s effect on endothelial cells.

Potential of Photoelectric Stimulation with Ultrasmall Carbon Electrode on Neural Tissue: New Directions in Neuromodulation Technology Development

“…7). The PEDOT/SNP system presents a versatile platform for loading and releasing a wide range of drugs, including essential neurotransmitters such as glutamate, the inhibitory transmitter GABA, as well as dopamine (DA), 6,7-Dinitroquinoxaline-2,3-dione (DNQX), and bicuculline [89, 90, 92]. Thus, it holds promise for biochemical modulation using light-controlled, minimally invasive photoelectric electrodes to study the mechanisms of neural circuits involved in both normal and pathological cognition.…”

Fully flexible implantable neural probes for electrophysiology recording and controlled neurochemical modulation

“…Drug release pro le determination occurred by applying the stimulation signal (2Hz, 0 ± 0.5V) to the chemical sites in the PBS. The PEDOT lm is reduced by the applied waveform pulses, resulting in structure opening, thereby allowing PBS to penetrate the spaces where the SNPs are caged 20 . The drug diffuses out of the nanoparticle pores into the PBS, which is ushed back out after each stimulation.…”

Finite-element modeling of neuromodulation via controlled delivery of potassium ions using conductive polymer-coated microelectrodes

“…CP-coated electrodes can modulate the local ionic concentration upon application of an electrical stimulus which translates into the injection of holes 6 (or electrons) in the polymer backbone and is followed by the release of pre-charged cations (or anions) in the target electrolyte. The pre-charging can be achieved using the electrostatic forces provided by fixed moieties in the CP blend or when the charged drugs act as dopants [18][19][20]. In the purely electrostatic CP loading, selectivity can be achieved by adding ionophores [21][22][23], using ion-selective membranes [24] or cell membrane bilayers with specific ion-channel expressions [25].…”