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Honolulu, HI, United States, 2006/02/23 - Researchers from the Martin Research Group at the University of Michigan have demonstrated they can precisely release individual drugs and bioactive molecules at desired points in time by using electrical stimulation of nanotubes..
"There are many potential applications of our work" Professor Martin told Nanowerk "since we have demonstrated the ability to precisely control both the spatial and temporal delivery of drugs using the polymer nanotubes. This means the drugs now come out when we want them and where we want them."
Martin's research provides a means for creating low impedance, biologically active polymer coatings, allowing the development of highly biocompatible electrodes that facilitate integration at the electrode -living tissue interface. Apart from precise drug-delivery, the potential biomedical applications of these molecule- eluting, electrically active polymer nanotubes could include highly localized stimulation of neurite outgrowth and guidance for neural tissue regeneration through functionalizing microelectrodes on neural prostheses.
Conducting polymers are of considerable interest for researchers working on biomedical applications. Their response to electrochemical oxidation or reduction can produce a change in conductivity, color, and volume. Martin's group developed a method to prepare conducting-polymer nanotubes that can be used for precisely controlled drug release.
The fabrication process involves electrospinning of a biodegradable polymer, into which a drug has been incorporated, followed by electrochemical deposition of a conducting-polymer around the drug-loaded, electrospun biodegradable polymers. The conducting-polymer nanotubes significantly decrease the impedance and increase the charge capacity of the recording electrode sites on microfabricated neural prosthetic devices. The drugs can be released from the nanotubes in a desired fashion by electrical stimulation of the nanotubes.
A big problem with the implantation of microelectrodes and neural prosthetic devices in the nervous system is associated with tissue injury and inflammation. This results in neuronal loss near electrodes and encapsulation of the device in a high impedance barrier of glia and immune cells, undermining the goal of maintaining long-term communication with neurons. Minimizing the electrode impedance therefore is an important requirement for obtaining highquality signals (high signal-to-noise ratio).
Martin believes that both the biocompatibility and electrical signal transduction capacity of neural prosthetic devices and deep brain stimulators can be greatly enhanced by integration with the technology that they are developing. His studies have shown that PEDOT (the conducting polymer poly(3,4-ethylene dioxythiophene)) can be polymerized around living cells and tissues with little toxicity. This suggests that PEDOT networks can be grown within living tissue, for the purpose of extending electrodes to contact healthy neurons beyond the halo of dead cells and inflammatory tissue that encapsulates chronically implanted neural prosthetics.
A variety of proteins, including Nerve Growth Factor, collagen, laminin, and poly(lysine) can be incorporated into the PEDOT matrix. Protein within the PEDOT is bioactive. It can be recognized by cells in contact with the PEDOT and can be passively or actively released from the polymer matrix.
In their recent work, Martin describes how they prepared drug-loaded PEDOT nanotubes on the surface of a microelectrode. The process starts by electrospinning nanofibers of the biodegradable polymer PLGA (poly(lactide-co-glycolide)) onto the surface of a neural probe followed by electrochemical deposition of conducting polymers around the electrospun nanofibers. In a final step, the fiber templates can be removed or allowed to slowly degrade, providing additional means of controlled delivery of biologically active agents incorporated into the fibers themselves.
The nanotubes deliver their bioactive contents either by passive delivery resulting from controlled degradation of the PLLA/PLGA or other matrix polymer used in the core or by actively actuating the drug-loaded nanotubes with an applied electrical field.
Professor Martin's article, titled "Conducting-Polymer Nanotubes for Controlled Drug Release" was published in the Jan. 25, 2006 online edition of Avanced Materials.
By Michael Berger, Copyright 2006 Nanowerk LLC