Department of Anesthesiology, Division of Critical Care Medicine , Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue , Boston , Massachusetts 02115 , United States.
Mol Pharm. 2019 Apr 1;16(4):1555-1562. doi: 10.1021/acs.molpharmaceut.8b01235. Epub 2019 Mar 6.
Acute otitis media (AOM) commonly causes pain and distress in children. Existing analgesic ototopical drops have limited effectiveness due to the impermeable nature of the tympanic membrane. We developed a local drug delivery system to provide sustained pain relief in patients with AOM, achieved by applying a single dose of a hydrogel formulation onto the tympanic membrane. Successful drug delivery across intact tympanic membranes was demonstrated using the amino-amide anesthetic, bupivacaine, and a highly potent site 1 sodium channel blocker anesthetic, tetrodotoxin. The chemical permeation enhancers incorporated in the delivery system increased the permeability of the tympanic membrane to the anesthetics considerably. The drug levels measured using a previously developed ex vivo model reflect the potential for highly effective local anesthesia.
急性中耳炎（AOM）常导致儿童疼痛和不适。由于鼓膜的不可渗透性，现有的镇痛耳用滴剂效果有限。我们开发了一种局部药物递送系统，通过在鼓膜上施用单剂量的水凝胶制剂，为 AOM 患者提供持续的疼痛缓解。使用氨基酰胺麻醉剂布比卡因和高效位点 1 钠通道阻滞剂麻醉剂河豚毒素成功地实现了穿过完整鼓膜的药物递送。递药系统中包含的化学渗透增强剂大大增加了鼓膜对麻醉剂的通透性。使用先前开发的离体模型测量的药物水平反映了局部麻醉高度有效的潜力。
