# Optimizing Delivery of a Known Therapeutic Agent, Dexamethasone, to Improve Microelectrode Recording Performance

> **NIH VA I01** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2021 · —

## Abstract

The overall goal of this proposal is to improve the chronic performance of intracortical recording microelectrodes
using a targeted drug-delivery approach. Microelectrode-based devices have the potential to resolve many
challenges in rehabilitation for Veterans with paralysis and/or amputation. Notably, brain-computer interface
(BCI) endeavors within the VA have provided patients the ability to control electromechanical or neuromuscular
prostheses using ‘thoughts’ or signals from their motor cortex. BCIs are further being extended by researchers
at the VA to restore the sensation of touch by integrating sensors and stimulators into mechanical prosthetic
limbs.3-5 While the promises of intracortical microelectrode interfaces are significant, the devices suffer from a
key challenge: long term stability and functionality. The failure modes are multifaceted, but a substantial
component is attributed to vascular trauma from implantation that initiates bleeding and a prolonged biological
response, including inflammation which leads to significant reduction in healthy neurons near recording contacts.
Several FDA-approved drugs have demonstrated the ability to reduce the biological inflammatory response and
augment microelectrode recording performance in rodents. However, due to limitations of pharmacokinetics and
pharmacodynamics, most of the agents reach the implant site in relatively low concentrations, limiting the
magnitude of effect and/or requiring frequent dosages to attain meaningful results. Additionally, in the case of
steroids and antibiotics, long-term systemic administration is contraindicated due to side effects on peripheral
systems. Leveraging a platelet-inspired drug delivery platform currently undergoing commercialization, we have
engineered a method for targeting drugs specifically to the microelectrode implantation site. Localizing the drug
to the microelectrode site will reduce the systemically administered dose, while minimizing the payload delivered
to peripheral organs, e.g., liver and kidneys. During this study, we will focus on delivering the drug,
dexamethasone (Dex), which is a potent glucocorticoid steroidal anti-inflammatory drug. While we have
demonstrated the ability to target the microelectrode with drug-loaded nanoparticles, further optimization of
dosing with Dex and characterization of chronic recordings are needed. Our objective is to establish a safe and
effective drug-delivery platform for localized therapy to improve chronic BCI performance. We hypothesize that
administration of targeted dexamethasone-loaded nanoparticles (Dex-NPs) will prevent chronic scarring and
neurodegeneration associated with improved chronic recording quality of intracortical microelectrodes and
associated motor-behavioral function. If proven effective, the platform may be further developed and
characterized to release other pharmaceutical payloads that have unique or complementary effects on the
system. Additionally since the delivery plat...

## Key facts

- **NIH application ID:** 10217285
- **Project number:** 5I01RX003420-02
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Jeffrey R Capadona
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217285

## Citation

> US National Institutes of Health, RePORTER application 10217285, Optimizing Delivery of a Known Therapeutic Agent, Dexamethasone, to Improve Microelectrode Recording Performance (5I01RX003420-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10217285. Licensed CC0.

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