Fig. 4: In vivo performance of TTX formulations.

a Schematic of liposomes encapsulating tetrodotoxin, injection at the sciatic nerve, and prolonged duration local anesthesia due to blockade of voltage-gated sodium channels. b Duration of sensory nerve blockade from different formulations injected at the sciatic nerve. Daggers indicate 100% mortality. Data are presented as means ± SD. n = 4 biologically independent animals. P-values are from unpaired two-tailed t-test. P = 0.333 comparing TTX@Lipo at 24.8 µg TTX and ICG + TTX@Lipo at 24.4 µg; **P = 0.007 comparing ICG + TTX@Lipo at 31.0 µg TTX and TTX@Lipo-Ph at 32.1 µg TTX. c Frequency of block in the contralateral (uninjected) leg. d Mortality from different formulations. Deaths occurred within the first 0.5 h after injection in animals treated with free TTX, within 0.5–1.0 h in animals treated with TTX@Lipo, and within 0.7–1.5 h in animals injected with TTX + ICG@Lipo. In b–d, navy triangle, green square, pink diamond, and orange circle represent free TTX, liposomes encapsulating TTX (TTX@Lipo), liposomes encapsulating TTX and ICG (ICG + TTX@Lipo) and aromatized liposomes encapsulating TTX (TTX@Lipo-Ph), respectively. e Effect of epinephrine (green circle) and dexamethasone (orange square) on the duration of nerve block from TTX@Lipo-Ph. Data are presented as mean ± SD, n = 4 biologically independent animals.