Conducting polymers, dual neurotrophins and pulsed electrical stimulation — Dramatic effects on neurite outgrowth

• Published in: Journal of controlled release Vol. 141; no. 2; pp. 161 - 167
• Main Authors: Thompson, Brianna C., Richardson, Rachael T., Moulton, Simon E., Evans, Alison J., O'Leary, Stephen, Clark, Graeme M., Wallace, Gordon G.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 25.01.2010; Elsevier
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - chemistry; Brain-Derived Neurotrophic Factor - pharmacology; Cell Survival; Cochlear Nerve - drug effects; Cochlear Nerve - growth & development; Drug Carriers; Drug Combinations; Drug Synergism; Electric Conductivity; Electric Stimulation; Electrical stimulation; General pharmacology; Kinetics; Medical sciences; Neural engineering; Neurites - drug effects; Neurotrophin 3 - chemistry; Neurotrophin 3 - pharmacology; Neurotrophin-3; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymers - chemistry; Polypyrrole; Pyrroles - chemistry; Rats; Rats, Wistar; Solubility; Tissue Culture Techniques; Electrical stimulation; Neurotrophin-3; Brain-derived neurotrophic factor; Neural engineering; Polypyrrole; Neurotrophin; Neurotrophic factor; Neurite; Pharmaceutical technology; Polymer; Encephalon; Growth factor
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2009.09.016

In this study the synergistic effect of delivering two neurotrophins simultaneously to encourage neuron survival and neurite elongation was explored. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were incorporated into polypyrrole (PPy) during electrosynthesis and the amounts incorporated and released were determined using iodine-125 ( 125I) radio-labelled neurotrophins. Neurite outgrowth from cochlear neural explants grown on the conducting polymer was equivalent to that on tissue culture plastic but significantly improved with the incorporation of NT-3 and BDNF. Neurite outgrowth from explants grown on polymers containing both NT-3 and BDNF showed significant improvement over PPy doped only with NT-3, due to the synergistic effect of both neurotrophins. Neurite outgrowth was significantly improved when the polymer containing both neurotrophins was electrically stimulated. It is envisaged that when applied to the cochlear implant, these conducting and novel polymer films will provide a biocompatible substrate for storage and release of neurotrophins to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes. [Display omitted]