Nanoparticle-driven systems for tunable local pain relief

纳米颗粒驱动系统可调节局部疼痛缓解

• 批准号: 9003513
• 负责人: Daniel S Kohane
• 金额: $ 34.07万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9003513
• 关键词: Absence of pain sensation; Acute Pain; Adverse effects; Affect; Biodistribution; Characteristics; Chronic; Clinical; Data; Development; Devices; Disadvantaged; Dose; Drug Delivery Systems; Effectiveness; Formulation; Gold; Heating; Individual; Inflammatory Response; Injectable; Injury; Lasers; Light; Local Anesthetics; Local Therapy; Local anesthesia; Medical; Membrane; Methods; Microfluidics; Modeling; Motor; NanoGel; Nanostructures; Nerve; Nerve Block; Outpatients; Pain; Pain management; Patients; Performance; Pharmaceutical Preparations; Polymers; Population; Porosity; Postoperative Pain; Postoperative Period; Productivity; Rattus; Reporting; Safety; Sensory; Site; Sodium Channel Blockers; System; Temperature; Testing; Tetrodotoxin; Time; Tissues; Toxic effect; Translations; United States; Validation; addiction; attenuation; base; capsule; chronic pain; cost; design; exhaust; heat injury; implantation; in vivo; interest; irradiation; microvesicles; nanocomposite; nanoparticle; public health relevance; sciatic nerve

 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.

 描述（由申请人提供）：用全身药物治疗慢性或长期急性疼痛常常不成功或充满副作用，例如成瘾和耐受性。在这里，我们建议开发局部/区域性疼痛治疗方法，可以根据患者的意愿调整持续时间和强度。这些装置将是可植入或可注射的药物输送系统，由膜包围，当受到近红外（NIR）光照射时，膜的孔隙率会增加。近红外光导致设备内部的金纳米结构升温，进而导致膜内的纳米凝胶塌陷，打开允许药物流动的孔。该应用的一个关键部分是设计方法，使纳米凝胶在很少的照射下塌陷，以尽量减少组织损伤。这些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。所使用的局部麻醉剂是超强效 1 号位点钠通道阻滞剂河豚毒素，可以单独使用，也可以与增强其神经阻滞作用的药物联合使用。