Dexamethasone-loaded platelet-inspired nanoparticles improve intracortical microelectrode recording performance

Long-term robust intracortical microelectrode (IME) neural recording quality is negatively affected by the neuroinflammatory response following microelectrode insertion. This adversely impacts brain-machine interface (BMI) performance for patients with neurological disorders or amputations. Recent studies suggest that the leakage of blood-brain barrier (BBB) and microhemorrhage caused by the IME insertions lead to the increased neuroinflammation and reduced neural recording performance. Additionally, a sustained presence of activated platelets and coagulation factors is found near the insertion site. Thus, we hypothesized that the systemic administration of dexamethasone sodium phosphate-loaded platelet-inspired nanoparticle (SPPINDEX) can improve the neural recording performance of intracortical microelectrodes (IMEs) by promoting hemostasis, facilitating blood-brain barrier (BBB) healing, and achieving implant-targeted drug delivery. Leveraging the hemostatic and coagulation factor-binding properties of the platelet-inspired nanoparticle (PIN) drug delivery platform, SPPINDEX treatment can initially attenuate the invasion of neuroinflammatory triggers into the brain parenchyma caused by insertion-induced microhemorrhages or a compromised BBB. Furthermore, targeted delivery of the anti-inflammatory drug dexamethasone sodium phosphate (DEXSP) to the implant site via these nanoparticles can attenuate ongoing neuroinflammation, enhancing overall therapeutic efficacy. Weekly treatment with SPPINDEX for 8 weeks significantly improved the recording capabilities of IMEs compared to platelet-inspired nanoparticles alone (PIN), free dexamethasone sodium phosphate (Free DEXSP), and a diluent control trehalose buffer (TH), as assessed through extracellular single-unit recordings. Immunohistochemical analyses of neuron density, activated microglia/macrophage density, astrocyte density, and BBB permeability suggest that the improved neural recording performance may be attributed to reduced neuron degeneration, activated microglia and astrocytes at the implant interface caused by the decreased infiltration of blood-derived proteins that trigger neuroinflammation and the therapeutic effects from DEXSP. Overall, SPPINDEX treatment promotes an anti-inflammatory environment that improves neuronal density and enhances recording performance.