Electrophoretic Delivery of Clinically Approved Anesthetic Drug for Chronic Pain Therapy

Abstract

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 (Ca 2+ 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.

Bioelectronic Devices for Targeted Drug Delivery and Monitoring of Microbial Electrogenesis

“…OMIEC materials in turn led to the emergence of a parallel branch of organic electronics termed as "Iontronics" which essentially comprises of materials and devices that shows dual ionic-electronic capabilities. And just like in electronics, the field of iontronics too have devices such as transistors [7], diodes [8]- [12] and resistors [13]- [16]. Thus far Poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT: PSS) is the most commonly reported OMIEC material owing to its commercial availability and water-based solution processibility.…”

“…OEIPs have evolved over multiple generations from being able to deliver small yet biologically relevant ions such as potassium, sodium [13] to pharmaceutically relevant analgesics [16] largely in part due to the advancements made in the IEM technology.…”

“…In paper#2 [16], we discussed the simultaneous real time electrophoretic delivery of bupivacaine to DRG neurons and calcium imaging to prove the concept of targeted delivery of local analgesics to the DRG neurons using capillary based OEIP devices. In short, we first dyed the DRG neurons (harvested from a BALB/c female mice) with a calcium indicator fluo-3AM.…”