Nerve pain affects millions of people, and can be personally devastating for people who experience it. Current methods for pain management (e.g. local injection of pain killers) are inadequate because of the short duration of action. Even sustained release treatments, such as drug-loaded liposomes, provide only one week of analgesia producing a continuous extended nerve blockade without allowing for changes in daily physical activity or level of pain relief. More importantly, such systems cannot be turned off until they run their course.
In this proposal, a locally-injected or implanted near infrared (NIR)-sensitive drug reservoir that can be triggered by a simple handheld laser device applied externally is described. The device enables drug release with consistent response over multiple on/off cycles. Such a device, implanted (or eventually injected) on a nerve or near the neuraxis, could have substantial clinical impact in the treatment of chronic (or prolonged perioperative) pain.
This system will consist of an impermeable ethylcellulose membrane embedded with temperature-sensitive polymer nanoparticles and NIR-active gold nanoparticles. The membrane will be engineered such that the nanoparticles form a disordered but interconnected network throughout. The gold nanoparticle concentration will be adjusted so that light-induced heating of the nanoparticles produces sufficient heat to collapse the polymer, thus opening the porous network. Those nanostructured materials which compose the device will be produced in a continuous manner by using microfluidic reactors to avoid the characteristic disadvantages when using conventional discontinuous (batch) reactors. Nanoparticle-synthesis protocols will be supported by computational fluid dynamics.
The specific aims will be geared toward engineering a NIR-triggered drug release device and optimizing for a variety of drug types, then demonstrating its biocompatibility and therapeutic effectiveness in vivo.
Fields of science
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