Nanoparticle-driven systems for tunable local pain relief

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 DESCRIPTION (provided by applicant): The treatment of chronic or prolonged acute pain with systemic medications is frequently unsuccessful or fraught with side effects such as addiction and tolerance. Here we propose to develop local / regional local treatments of pain that could be adjusted at will in duration and intensity by the patient. The devices will be implantable or injectable drug delivery systems bounded by membranes that increase in porosity when irradiated by near-infrared (NIR) light. The NIR light causes gold nanostructures inside the devices to heat up, which in turn causes nanogels within the membrane to collapse, opening pores that allow drug flux. A key part of this application is designing methods to allow the nanogels to collapse with very little irradiation, to minimize tissue injury. The devices will be rendered as implantable capsules and as injectable microvesicles, and tested in a rat sciatic nerve block model. The local anesthetic to be delivered is the ultra-potent site 1 sodium channel blocker tetrodotoxin, alone and in combination with drugs that increase its effects on nerve block.