In order to address material limitations of biologically interfacing electrodes, modified silica nanoparticles are utilized as dopants for conducting polymers. Silica precursors are selected to form a thiol modified particle (TNP), following which the particles are oxidized to sulfonate modified nanoparticles (SNPs). The selective inclusion of hexadecyl trimethylammonium bromide allows for synthesis of both porous and nonporous SNPs. Nonporous nanoparticle doped polyethylenedioxythiophene (PEDOT) films possess low interfacial impedance, high charge injection (4.8 mC cm−2), and improved stability under stimulation compared to PEDOT/poly(styrenesulfonate). Porous SNP dopants can serve as drug reservoirs and greatly enhance the capability of conducting polymer‐based, electrically controlled drug release technology. Using the SNP dopants, drug loading and release is increased up to 16.8 times, in addition to greatly expanding the range of drug candidates to include both cationic and electroactive compounds, all while maintaining their bioactivity. Finally, the PEDOT/SNP composite is capable of precisely modulating neural activity in vivo by timed release of a glutamate receptor antagonist from coated microelectrode sites. Together, this work demonstrates the feasibility and potential of doping conducting polymers with engineered nanoparticles, creating countless options to produce composite materials for enhanced electrical stimulation, neural recording, chemical sensing, and on demand drug delivery.
BackgroundOxidative stress acts as a trigger in the course of neurodegenerative diseases and neural injuries. An antioxidant-based therapy can be effective to ameliorate the deleterious effects of oxidative stress. Resveratrol (RSV) has been shown to be effective at removing excess reactive oxygen species (ROS) or reactive nitrogen species generation in the central nervous system (CNS), but the delivery of RSV into the brain through systemic administration is inefficient. Here, we have developed a RSV delivery vehicle based on polylactic acid (PLA)-coated mesoporous silica nanoparticles (MSNPs), conjugated with a ligand peptide of low-density lipoprotein receptor (LDLR) to enhance their transcytosis across the blood–brain barrier (BBB).ResultsResveratrol was loaded into MSNPs (average diameter 200 nm, pore size 4 nm) at 16 μg/mg (w/w). As a gatekeeper, the PLA coating prevented the RSV burst release, while ROS was shown to trigger the drug release by accelerating PLA degradation. An in vitro BBB model with a co-culture of rat brain microvascular endothelial cells (RBECs) and microglia cells using Transwell chambers was established to assess the RSV delivery across BBB. The conjugation of LDLR ligand peptides markedly enhanced the migration of MSNPs across the RBECs monolayer. RSV could be released and effectively reduce the activation of the microglia cells stimulated by phorbol-myristate-acetate or lipopolysaccharide.ConclusionsThese ROS responsive LDLR peptides conjugated PLA-coated MSNPs have great potential for oxidative stress therapy in CNS.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0340-7) contains supplementary material, which is available to authorized users.
Neurotechnology is facing an exponential growth in the recent decades. Neural electrode-tissue interface research has been well recognized as an instrumental component of neurotechnology development. While satisfactory long-term performance was demonstrated in some applications, such as cochlear implants and deep brain stimulators, more advanced neural electrode devices requiring higher resolution for single unit recording or microstimulation still face significant challenges in reliability and longevity. In this article, we review the most recent findings that contribute to our current understanding of the sources of poor reliability and longevity in neural recording or stimulation, including the material failure, biological tissue response and the interplay between the two. The newly developed characterization tools are introduced from electrophysiology models, molecular and biochemical analysis, material characterization to live imaging. The effective strategies that have been applied to improve the interface are also highlighted. Finally, we discuss the challenges and opportunities in improving the interface and achieving seamless integration between the implanted electrodes and neural tissue both anatomically and functionally.
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