Repeatable and adjustable on-demand local anesthesia using externally-triggerable liposomes

Abstract

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients, with the desired intensity and duration. Current treatment for many pain states - including localized pain - often involves systemic medications such as opioids that have significant side effects. Externally triggerable drug delivery systems provide a strategy for the delivery of therapeutic agents preferentially to the target site at the desired timing, dosage, and duration, presenting the ability to enhance therapeutic efficacy while reducing side effects. Here we have developed light- and ultrasound- triggerable liposomes that provide on-demand nerve block at the desired timing, intensity and duration. The responsiveness of the liposomes towards the external triggering was studied in vitro, where the light triggerable system showed 5.6% drug release upon irradiation with 730 nm light and the ultrasound triggerable system showed 5.4% drug release upon insonation 1 MHz, 3W/cm² ultrasound. Sciatic nerve blockades for up to a duration of 2h was successfully achieved with safe dosage of light (730 nm, 75 mW/cm², 15 min) or ultrasound (1 MHz, 3W/cm², 10 min). Sciatic nerve block could be triggered repeatedly with light or ultrasound for more than 5 times upon a single injection. The duration of nerve block showed a linear relationship with the energy density of the triggering event, which was controlled by duration and intensity of the external energy source. Tissue reaction was benign. Such on-demand nerve block systems have promising potential to provide personalized and effective local anesthesia that will enhance pain management.