4.4 Article

Electrophoretic Delivery of Clinically Approved Anesthetic Drug for Chronic Pain Therapy

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ADVANCED THERAPEUTICS
卷 6, 期 7, 页码 -

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WILEY
DOI: 10.1002/adtp.202300083

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anesthetic; bupivacaine; calcium imaging; drug delivery; electrophoretic; ion exchange membrane

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The authors demonstrate the effective delivery of the commonly used analgesic drug bupivacaine to DRG neurons via organic electronic ion pumps (OEIPs) without fluid flow. Only cells close to the OEIP outlet are affected, at concentrations significantly lower than with bulk/bolus delivery. This achievement represents a significant milestone for the translation of this technology.
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 mu m) 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.

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