RESUMEN
On-demand relief of local pain would allow patients to control the timing, intensity and duration of nerve block in a safe and non-invasive manner. Ultrasound would be a suitable trigger for such a system, as it is in common clinical use and can penetrate deeply into the body. Here, we demonstrate that ultrasound-triggered delivery of an anaesthetic from liposomes allows the timing, intensity and duration of nerve block to be controlled by ultrasound parameters. On insonation, the encapsulated sonosensitizer protoporphyrin IX produces reactive oxygen species that react with the liposomal membrane, leading to the release of the potent local anaesthetic tetrodotoxin. We also show repeatable ultrasound-triggered nerve blocks in vivo, with nerve-block duration depending on the extent and intensity of insonation. We did not detect any systemic toxicity, and tissue reaction was benign in all groups. On-demand, personalized local anaesthesia could be beneficial for the managing of relatively localized pain states, and potentially minimize opioid use.