Cooling-triggered sciatic nerve block using thermoresponsive hydrogel implants

Abstract Opioids remain the standard of post-operative pain management despite their known addiction risks. Local anesthetics, like bupivacaine, offer a safer, non-systemic alternative; however, existing delivery methods are either inconvenient, painful, or require complex equipment. Herein, we describe an implantable drug delivery device that leverages the cooling-triggered, reversible gel-to-sol transition of poly-N-isopropylacrylamide [PNIPAM] (achieved by simple icepack cooling, a pain-relief strategy already familiar to patients) for on-demand release of bupivacaine hydrochloride. Conveniently, this system allows on/off drug release over multiple cycles, as the drug release rate is significantly reduced when the cooling stimulus is removed but can be restored upon subsequent reapplication of cooling. We detail device fabrication and cooling-triggered release testing of a model dye and the drug of interest both in vitro and in vivo, with thermal latency testing on Sprague-Dawley rats used to demonstrate cooling-triggered sensory nerve block. Our results establish cooling as an intuitive trigger for delivery of local anesthetics, offering a promising route to patient-controlled, repeatable pain relief that could reduce opioid dependency in post-operative care.