Fig. 6: Noninvasive nerve block with in vivo AAL-mediated ultrasonic ropivacaine uncaging. | Nature Nanotechnology

Fig. 6: Noninvasive nerve block with in vivo AAL-mediated ultrasonic ropivacaine uncaging.

From: Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Fig. 6

a, Adult rats (n = 8 per group) received a 5 min intravenous infusion of saline or a ropivacaine-loaded AAL (S5-RL from prior, now SonoRopi; 5 mg kg−1), with FUS (250 kHz, 25% duty cycle, 5 Hz PRF, 0.9 MPa estimated in situ peak negative pressure) applied externally transcutaneously to target the sciatic nerve of the left limb for 2.5 min during the latter half of a 5 min infusion. Frequency of paw withdrawal to a mechanical stimulus (von Frey test) was assayed before and after infusion and sonication (https://BioRender.com/dixj6am). b, In saline- and FUS-treated animals, no significant difference in mechanical sensitivity was seen across time or between the limb ipsilateral (ipsi) to sonication versus the limb contralateral (contra) to sonication. c, In SonoRopi- and FUS-treated animals, significant differences in mechanical sensitivity were seen in the limb ipsilateral to sonication at certain time points after sonication and infusion versus the baseline (red asterisks; BL versus 0.5 h P = 0.0175, BL versus 1 h P = 0.0018), and between the limb ipsilateral to sonication versus contralateral to sonication (black asterisks; P = 0.0105). d–f, Electrocardiographic parameters recorded at baseline (BL), at the start of infusion (0 min) and the end of infusion (5 min) of 5 mg kg−1 ropivacaine-HCl or SonoRopi (n = 3 per group) show no significant differences of PR interval duration (PRD; d), QRS interval duration (QRSD; e), and corrected QT interval duration (QTcD; f). g–k, Schematic (g) and representative images (h–k) for histological safety analysis with H&E staining of rats receiving the indicated treatment to the sciatic nerve of rats (n = 3 rats per group) showed no concerning parenchymal damage when analyzing muscle tissue in the region of interest in cross section (h) and longitudinally (i), or analyzing the treated sciatic nerve (j) and the nearby femoral artery (k).(https://biorender.com/b3028oe). Data presented as mean ± s.e. (b,c) or s.d. (d–f). Comparisons between multiple groups performed by two-way ANOVA; *P < 0.05, **P < 0.01 and ***P < 0.001.

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