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

基本信息

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
项目类别：
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

项目摘要

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。在此，我们建议开发可随意调整的局部/区域局部疼痛治疗方法。该装置将是可植入或可注射的药物输送系统，其周围有膜，当受到近红外 (NIR) 光照射时，膜的孔隙率会增加。近红外光会在装置内部形成金纳米结构。加热，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使纳米凝胶在很少的照射下塌陷的方法，以最大限度地减少组织损伤。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。待输送的局部麻醉剂是超强效的1位点钠通道阻滞剂河鲀毒素，单独使用或与河鲀毒素混合使用。与增加神经阻滞作用的药物联合使用。