Ultrasound-triggered local anaesthesia

Abstract

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.

Retracted: Ultrasound‐triggered breast tumor sonodynamic therapy through hematoporphyrin monomethyl ether‐loaded liposome

“…Use of ultrasound with lower frequency and power improves the cavitation and concomitant biological effect (Hu et al, ; Qian, Zheng, & Chen, ). Multiple studies have shown that some sensitizers can be efficiently activated by ultrasound and generates cytotoxic ROS (Giuntini et al, ; Li et al, ; Rwei et al, ). Recently, a lot of sonosensitizers has been applied in SDT, including TiO 2 , chlorin, phthalocyanines and photofrin (Osaki et al, ; Rwei et al, ; Xu et al, ).…”

“…Multiple studies have shown that some sensitizers can be efficiently activated by ultrasound and generates cytotoxic ROS (Giuntini et al, ; Li et al, ; Rwei et al, ). Recently, a lot of sonosensitizers has been applied in SDT, including TiO 2 , chlorin, phthalocyanines and photofrin (Osaki et al, ; Rwei et al, ; Xu et al, ). Among them, hematoporphyrin monomethyl ether (HMME), a newly approved sonosensitizer by SFDA, displays good potential in the application of SDT (Li, Song, Xu, Huang, & Yue, ; Nelson et al, ).…”

“…sonosensitizers has been applied in SDT, including TiO 2 , chlorin, phthalocyanines and photofrin (Osaki et al, 2016;Rwei et al, 2017;Xu et al, 2015). Among them, hematoporphyrin monomethyl ether (HMME), a newly approved sonosensitizer by SFDA, displays good potential in the application of SDT (Li, Song, Xu, Huang, & Yue, 2008;Nelson et al, 2018).…”

Focused shockwave induced blood-brain barrier opening and transfection

“…More and higher intensity shockwave treatment induced more and larger areas of bubbles in the phantoms, implying more cavitation activity leading to larger areas of BBB opening and tissue injury (i.e., red blood cells extravasation, apoptosis and glia cell infiltration). The extensive red blood cell extravasation produced by the addition of UCA is probably due to the high peak negative pressure of the shockwaves and strong cavitation effect in the rat brains (see Table 1 for detailed parameters) 24–26 .

Figure 9Bubbles generated after 0, 50, and 100 shocks at PRF 5 Hz and intensity levels of 10 and 5.

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“…Shockwaves are well known to produce cavitation 24 , which is believed to be the major mechanism responsible for opening the BBB by HIFU 25,26 . Furthermore, focused shockwaves operate at a lower frequency than ultrasound, thus offering better penetration.…”