Laboratory for Biomaterials and Drug Delivery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Medical Critical Care, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Drug Deliv Transl Res. 2020 Oct;10(5):1507-1516. doi: 10.1007/s13346-020-00760-1.
The effect of local anesthetics, particularly those which are hydrophilic, such as tetrodotoxin, is impeded by tissue barriers that restrict access to individual nerve cells. Methods of enhancing penetration of tetrodotoxin into nerve include co-administration with chemical permeation enhancers, nanoencapsulation, and insonation with very low acoustic intensity ultrasound and microbubbles. In this study, we examined the effect of acoustic intensity on nerve block by tetrodotoxin and compared it to the effect on nerve block by bupivacaine, a more hydrophobic local anesthetic. Anesthetics were applied in peripheral nerve blockade in adult Sprague-Dawley rats. Insonation with 1-MHz ultrasound at acoustic intensity greater than 0.5 W/cm improved nerve block effectiveness, increased nerve block reliability, and prolonged both sensory and motor nerve blockade mediated by the hydrophilic ultra-potent local anesthetic, tetrodotoxin. These effects were not enhanced by microbubbles. There was minimal or no tissue injury from ultrasound treatment. Insonation did not enhance nerve block from bupivacaine. Using an in vivo model system of local anesthetic delivery, we studied the effect of acoustic intensity on insonation-mediated drug delivery of local anesthetics to the peripheral nerve. We found that insonation alone (at intensities greater than 0.5 W/cm) enhanced nerve blockade mediated by the hydrophilic ultra-potent local anesthetic, tetrodotoxin. Graphical abstract.
局部麻醉剂的效果，特别是那些亲水性的局部麻醉剂，如河豚毒素，会受到组织屏障的阻碍，这些组织屏障限制了其进入单个神经细胞的能力。增强河豚毒素渗透到神经中的方法包括与化学渗透增强剂共同给药、纳米封装以及用非常低的声强超声和微泡进行声处理。在这项研究中，我们研究了声强对河豚毒素引起的神经阻滞的影响，并将其与更亲脂性的局部麻醉剂布比卡因引起的神经阻滞效果进行了比较。麻醉剂应用于成年 Sprague-Dawley 大鼠的周围神经阻滞中。声强大于 0.5 W/cm 的 1 MHz 超声处理可提高神经阻滞效果、增加神经阻滞的可靠性，并延长亲水性超强效局部麻醉剂河豚毒素介导的感觉和运动神经阻滞。微泡并不能增强这些效果。超声处理对组织没有造成最小或没有损伤。超声处理也不会增强布比卡因引起的神经阻滞。在局部麻醉剂给药的体内模型系统中，我们研究了声强对局部麻醉剂经超声处理向周围神经传递的影响。我们发现，单独声处理（声强大于 0.5 W/cm）即可增强亲水性超强效局部麻醉剂河豚毒素介导的神经阻滞。
