On-demand drug delivery

On-demand drug delivery that provides precision drug release at the right time and location is highly desired as an advanced research tool and for personalized medicine. Towards this goal, we have developed an electrically controlled drug release system leveraging the electroactivity of conducting polymers as coatings for neural implants.

Initially, our drug delivery design incorporated conducting polymers with anionic drugs as dopants released via electrochemical reduction. Subsequently, we refined our approach by integrating nanostructures into the coatings. These enhancements encompassed nano-templating to craft a porous film, nano-layering for a sponge-like actuated drug release, and the incorporation of multiwall carbon nanotubes (CNTs), graphene oxide nanosheets, and mesoporous nanoparticles as drug carriers. The integration of nanomaterials significantly improved drug loading, tunability, and expanded the range of applicable drugs.

So far, we have demonstrated two in vivo uses for this drug delivery system: 1) we released glutamate and GABA from intracranial recording MEAs in live rats for transient, and reversible modulation of local neural activity upon brief electrical pulses and 2) we released a vasodilator into the mouse brain via carbon fiber electrodes and visualized increases in blood vessel diameter using live in vivo 2P-microscopy.

We also have developed mesoporous nanoparticles that release drugs in response to reactive oxygen species, a byproduct of tissue damage during electrode insertion. We continue to further characterize our current drug delivery methods, explore delivery of other drugs for therapeutic purposes as well as neurologic investigation, and explore other modalities for on-demand drug delivery from neural electrodes.

Relevant publications

• Woeppel, K. M., Krahe, D. D., Robbins, E. M., Vazquez, A. L. & Cui, X. T. Electrically Controlled Vasodilator Delivery from PEDOT/Silica Nanoparticle Modulates Vessel Diameter in Mouse Brain (Adv. Healthcare Mater. 3/2024). Adv Healthcare Materials 13, 2470019 (2024). [Link]
• Tan, C., Kushwah, N. & Cui, X. T. Electrically Controlled Neurochemical Delivery from Microelectrodes for Focal and Transient Modulation of Cellular Behavior. Biosensors 11, 348 (2021). [Link]
• Woeppel, K. M., Zheng, X. S., Schulte, Z. M., Rosi, N. L. & Cui, X. T. Nanoparticle Doped PEDOT for Enhanced Electrode Coatings and Drug Delivery. Advanced Healthcare Materials 8, 1900622 (2019). [Link]
• Du, Z. J., Bi, G. & Cui, X. T. Electrically Controlled Neurochemical Release from Dual‐Layer Conducting Polymer Films for Precise Modulation of Neural Network Activity in Rat Barrel Cortex. Adv Funct Materials 28, 1703988 (2018). [Link]
• Weaver, C. L., LaRosa, J. M., Luo, X. & Cui, X. T. Electrically Controlled Drug Delivery from Graphene Oxide Nanocomposite Films. ACS Nano 8, 1834–1843 (2014). [Link]
• Shen, Y. et al. ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier. J Nanobiotechnol 16, 13 (2018). [Link]