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Drug Delivery

Platelet-Inspired Nanoparticles Target Implanted Intracortical Microelectrodes

(L-461) Platelet-Inspired Nanoparticles Target Implanted Intracortical Microelectrodes

Saturday, October 14, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row L - Poster # 461

Presenting Author(s)

AH

Aniya Hartzler

Student Researcher
Case Western Reserve University
Cleveland, Ohio, United States

Co-Author(s)

Dm

Dhariyat menendez

Research Assistant
Case Western Reserve University, United States
LL

Longshun Li

Research Assistant
Case Western Reserve University, United States

Primary Investigator(s)

AS

Andrew Shofstall

Primary Investigator
Case Western Reserve University, United States

Introduction:: Three million people live with loss of motor function caused by spinal cord injury (SCI) and limb loss. Brain Machine Interfacing (BMI) has the potential to recover loss of motor function and increase the quality of life in patients. BMI can bypass damaged biological pathways enabling patients to finely control limbs or prosthetics with neural signals recorded by intracortical microelectrodes (IMEs). However, the use of BMI is limited by the decline in signal quality from the microelectrode over time, reducing the performance of BMIs. The performance decline is partly due to proinflammatory cells and proteins from the vascular trauma during implantation. Avoiding vascular trauma is nearly impossible, however, it may be possible to leverage the biological response and interrupt the inflammatory cascade. Platelet-inspired nanoparticles (PINs) selectively bind to damaged endothelium and activated platelets, mimicking the aggregation and adhesion properties of platelets at vascular injury sites. After targeting the injury site, PINs can deliver anti-inflammatory drugs that may enhance the recovery of IME implantation, reducing inflammation and increasing the longevity of signal recording. This study aims to determine the amount of PINs localization and the feasibility of using PINs as a targeted delivery for anti-inflammatory drugs around intracortical implantation sites.

Materials and Methods:: Rats (n=16 with four rats per treatment group) were implanted with four single-shank dummy probes, two per hemisphere. The rats were infused with one of four treatments: trehalose particle vehicle solution (TH), control nanoparticle (CP), once-per-week platelet-inspired nanoparticle (SP1), and twice-per-week platelet-inspired nanoparticle (SP2) through a pre-implanted catheter into the carotid artery. Animals were perfused after 4 weeks. Brains were explanted, fixed in formalin, and then cryoprotected with sucrose. Frozen brains were then sectioned transversely at 20 µm thickness and mounted onto charged slides for immunohistochemical staining. Slides were stained for three different markers: active microglia, BBB permeability, and activated platelets, and imaged using Zeiss auto-scanner. Images were analyzed with custom MATLAB software to quantify the intensity of fluorescence as a function of distance from the electrode hole.

Results, Conclusions, and Discussions:: Normalized average intensity for Cy5 (PINs and CP), CD62p (activated platelets), CD68 (microglia), IgG (BBB permeability) was plotted versus distance away from the implant site. In the range of 0-100 um of the implant site, the signal intensity for PINs (SP1 and SP2) and CP treatment is higher than the trehalose control. Preliminary results suggest that the twice per week PIN dosing was more concentrated around the implant site than the twice per week dosing. The CD68 and IgG staining was consistent with previous findings suggesting higher activated microglia and BBB leakage around the implant due to vascular trauma of the non-functional electrode probe. Furthermore, the CD62p staining for activated platelets was higher in the SP1 and SP2 dosing groups suggesting that PINs may promote increased aggregation or adhesion of activated platelets at the implant site. Our preliminary results suggest that the particles target the microelectrode implant site in a dose-dependent manner up to four weeks after surgery. We observed inflammatory and hemostatic proteins (CD62p, IgG and CD68) localized at the microelectrode implant site up to 4 weeks after surgery, consistent with the targeting ligands of the PINs. In conclusion, platelet-inspired nanoparticles have the potential to co-localize with inflammation at the electrode implant site for targeted, localized drug delivery.

Acknowledgements (Optional): :

This work was supported by the US Dept. of Veterans Affairs 1IS1BX004384, the Cleveland VA APT Center, Case Western Reserve University, and the NIH, 3T32EB004314-23S1. The opinions expressed in this article are the author's own and do not reflect the view of the Department of Veteran Affairs, National Institutes of Health, the Department of Health and Human Services, or the United States government.

References (Optional): :