Nanoparticle-driven systems for tunable local pain relief

 描述（由申请人提供）：使用全身药物治疗慢性或长期急性疼痛通常不成功或充满副作用，如成瘾和耐受性。在这里，我们建议开发局部/区域局部治疗疼痛，可以调整的时间和强度的病人。这些装置将是由膜限定的可植入或可注射的药物递送系统，当被近红外（NIR）光照射时，膜的孔隙率增加。近红外光使设备内部的金纳米结构升温，这反过来又导致膜内的纳米凝胶坍塌，打开允许药物流动的孔隙。该应用的一个关键部分是设计方法，使纳米凝胶在非常少的辐射下塌陷，以最大限度地减少组织损伤。该装置将被制成可植入胶囊和可注射微泡，并在大鼠坐骨神经阻滞模型中进行测试。待递送的局部麻醉剂是超强效部位1钠通道阻滞剂河豚毒素，单独使用或与增加其对神经阻滞作用的药物联合使用。

 DESCRIPTION (provided by applicant): The treatment of chronic or prolonged acute pain with systemic medications is frequently unsuccessful or fraught with side effects such as addiction and tolerance. Here we propose to develop local / regional local treatments of pain that could be adjusted at will in duration and intensity by the patient. The devices will be implantable or injectable drug delivery systems bounded by membranes that increase in porosity when irradiated by near-infrared (NIR) light. The NIR light causes gold nanostructures inside the devices to heat up, which in turn causes nanogels within the membrane to collapse, opening pores that allow drug flux. A key part of this application is designing methods to allow the nanogels to collapse with very little irradiation, to minimize tissue injury. The devices will be rendered as implantable capsules and as injectable microvesicles, and tested in a rat sciatic nerve block model. The local anesthetic to be delivered is the ultra-potent site 1 sodium channel blocker tetrodotoxin, alone and in combination with drugs that increase its effects on nerve block.