| Popis: |
Despite a range of available pain therapies, most patients report so-called “breakthrough pain.” Coupled with global issues like opioid abuse, there is a clear need for advanced therapies and technologies for safe and effective pain management. Here the authors demonstrate a candidate for such an advanced therapy: precise and fluid-flow-free electrophoretic delivery via organic electronic ion pumps (OEIPs) of the commonly used anesthetic drug bupivacaine. Bupivacaine is delivered to dorsal root ganglion (DRG) neurons in vitro. DRG neurons are a good proxy for pain studies as they are responsible for relaying ascending sensory signals from nociceptors (pain receptors) in the peripheral nervous system to the central nervous system. Capillary based OEIPs are used due to their probe-like and free-standing form factor, ideal for interfacing with cells. By delivering bupivacaine with the OEIP and recording dose versus response (Ca2+ imaging), it is observed that only cells close to the OEIP outlet (≤75 µm) are affected (“anaesthetized”) and at concentrations up to 10s of thousands of times lower than with bulk/bolus delivery. These results demonstrate the first effective OEIP deliveryof a clinically approved and widely used analgesic pharmaceutical, and thus are a major translational milestone for this technology. Funding agencies: This work was supported by the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the European Research Council (AdG 2018 Magnus Berggren, 834677 and CoG 2019 Camilla Svensson, 866075), and Vinnova. Additional support was provided by the Swedish Government Strategic Research Area in Materials Science on Advanced Functional Materials at Linköping University (Faculty Grant SFO-Mat-LiU no. 2009-00971). |
