Electrochemically triggered release of acetylcholine from scCO(2) impregnated conductive polymer films evokes intracellular Ca2+ signaling in neurotypic SH-SY5Y cells

摘要

Implantable devices for electronically triggered drug release are attractive to achieve spatial and temporal control over drug concentrations in patients. Realization of such devices is, however, associated with technical and biological challenges. Among these are containment of drug reservoirs, lack of precise control cues, as well as the charge and size of the drug. Here, we present a method for electronically triggered release of the quaternary ammonium cation acetylcholine (ACh) from an impregnated conductive polymer film. Using supercritical carbon dioxide (scCO(2)), a film of PEDOT/PSS (poly(3,4)-ethylenedioxythiophene doped with poly(styrenesulfonate)) is impregnated with the neurotransmitter acetylcholine. The gentle scCO(2) process generated a dry, drug-impregnated surface, well suited for interaction with biological material, while maintaining normal electrochemical properties of the polymer. Electrochemical switching of impregnated PEDOT/PSS films stimulated release of ACh from the polymer matrix, likely due to swelling mediated by the influx and efflux of charged and solvated ions. Triggered release of ACh did not affect the biological activity of the drug. This was shown by real-time monitoring of intracellular Ca2+ signaling in neurotypic cells growing on the impregnated polymer surface. Collectively, scCO(2) impregnation of conducting polymers offers the first one-step, dopant-independent drug impregnation process, potentially facilitating loading of both anionic and cationic drugs that can be dissolved in scCO(2) on its own or by using a co-solvent. We foresee that scCO(2)-loaded devices for electronically triggered drug release will create novel opportunities when generating active bio-coatings, tunable for specific needs, in a variety of medical settings. (C) 2016 Elsevier B.V. All rights reserved.