Externally-Triggerable Liposomes for Personalized, Non-Invasive Control of Local Anesthesia

Pain has a major impact on quality of life and affects billions of people worldwide. Yet, current treatments are either associated with significant side effects (i.e., opioids), suffer from insufficient durations of action (i.e., local anesthetics), or inability to provide adequate treatment with the patient’s changing physical conditions and pain states. Here we present externally-triggerable liposomes as a vehicle to provide spatio-temporal control of pain relief, enabling non-invasive control of the duration, intensity and timing of pain relief via external triggers, such as light and ultrasound. Inspired by the natural lipid degradation process via peroxidation, we have engineered near-infrared-light- and ultrasound-triggerable liposomes that encapsulate the local anesthetic tetrodotoxin. Our results show significant triggering of lipid peroxidation upon exposure to external energy, leading to the effective activation of drug release events. The drug release can be activated repeatedly upon exposure to the external trigger. <i>In vivo</i> results show successful generation of nerve block upon exposure to a low- and biocompatible dosage of near infrared light and/or ultrasound. These results demonstrate the promising potential of utilizing such systems for personalized pain therapy, in which patients can control the intensity, duration, and timing of therapy via light and/or ultrasound.