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Novel injectable analgesic delivery system for musculoskeletal pain management

用于肌肉骨骼疼痛管理的新型注射镇痛输送系统

基本信息

批准号：
9977127
负责人：
Lakshmi S Nair
金额：
$ 43.17万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9977127
关键词：
Absence of pain sensation Acute Address Adrenal Cortex Hormones American Analgesics Anesthetics Animal Model Anti Inflammatory Analgesics Anti-Inflammatory Agents Attention Attenuated Behavioral Biocompatible Materials Cell Line Cells Cessation of life Clinical Clinical Data Curcumin Degenerative polyarthritis Dexamethasone Diffusion Dose Drug Combinations Drug Delivery Systems Drug usage Effectiveness Electrophysiology (science)Engineering Epidemic Flare Formulation Future Goals Health Care Costs Hydrogels Hyperalgesia Impairment In Vitro Inflammation Injectable Injections Injury Intervention Iodoacetates Knee LOX gene Lead Ligation Lipids Local Anesthetics Low Back Pain Mechanics Mediator of activation protein Methylprednisolone Modeling Musculoskeletal Musculoskeletal Pain Musculoskeletal System Nerve Nerve Block Neuralgia Neuroglia Neurons Nociception Operative Surgical Procedures Opioid Opioid Rotation Oral Overdose Pain Pain intensity Pain management Patients Pharmaceutical Preparations Postoperative Period Process Property Quality of life Rattus Research Resolution Safety Schwann Cells Shoulder Signal Transduction Site Spinal Ganglia Testing United States Walkers analog attenuation base behavioral response clinical pain compliance behavior controlled release experience improved in vitro Model in vivo in vivo Model inhibitor/antagonist laurencin lipoxin A4 macrophage mechanical allodynia nanocapsule nanocomposite neurotoxicity novel opioid abuse opioid therapy opioid use outpatient facility pain model pain relief painful neuropathy perineural pre-clinical prescription opioid prevent response ropivacaine sciatic nerve side effect

项目摘要

Project Summary Acute flare-ups of musculoskeletal conditions (i.e., post-operative hyperalgesia, osteoarthritis, occipital neuralgia, and lower back pain) present as increased intensity of pain. Currently, opioids are prescribed to treat these flare- ups, making musculoskeletal pain one of the most frequent reasons for opioid prescriptions. Overdoses, abuses, diversions, and deaths from prescription opioids have reached epidemic proportions in the United States with associated healthcare costs of over $700 billion. Our long-term objective is to develop alternative, non-addictive interventions to treat flare-ups of musculoskeletal conditions. Our proposed research aims to develop injectable long-acting anesthetic formulations by combining local anesthetics with low doses of anti-inflammatory/analgesic pain modulators and sustained delivery of these drugs using engineered carriers. Preliminary studies showed the potential of synergistic drug combinations in conjunction with injectable hydrogel/lipid nanocapsule nanocomposites in prolonging local analgesia. We propose to evaluate clinically used corticosteroids as well as emerging analgesic pain modulators in conjunction with ropivacaine to identify the synergistic drug combinations. A diffusion- and degradation-controlled release process will be investigated for the sustained delivery of the analgesic pain modulators to prevent perineural inflammation and neurotoxicity. The in vivo assessment of the efficacy and safety of the formulations will be performed by following the behavioral and electrophysiological responses in rat models. An injectable long-acting formulation, which can be administered in an outpatient facility and can sustain local hypoalgesic effects for 7-14 days, would significantly enhance the quality of life for those suffering from flare-ups without the dire consequences of opioid therapy.

项目摘要肌肉骨骼疾病的急性发作(即术后痛觉过敏、骨关节炎、枕神经痛、和下背部疼痛)表现为疼痛强度增加。目前，阿片类药物是用来治疗这些耀斑的- UPS，使肌肉骨骼疼痛成为阿片类药物处方最常见的原因之一。吸毒过量，滥用，在美国，处方阿片类药物造成的分流和死亡已经达到流行的程度相关医疗成本超过7,000亿美元。我们的长期目标是开发替代的、不会上瘾的治疗肌肉骨骼疾病突发事件的干预措施。我们提议的研究旨在开发注射剂局麻药与低剂量抗炎/止痛剂联合使用的长效麻醉剂配方疼痛调节剂和使用工程载体的这些药物的持续输送。初步研究表明协同药物与可注射水凝胶/脂质纳米胶囊联合应用的潜力纳米复合材料在延长局部镇痛中的作用。我们建议评估临床使用的皮质类固醇以及新出现的止痛调节剂与罗比卡因联合使用，以确定协同药物组合。将研究扩散和降解控制释放过程，以实现该药物的持续释放止痛调节剂，以防止神经周围炎症和神经毒性。人血清白蛋白的体内评价这些配方的有效性和安全性将通过遵循行为和电生理在大鼠模型中的反应。一种可注射的长效制剂，可在门诊设施中使用并能维持7-14天的局部止痛效果，将显著提高这些患者的生活质量在没有阿片类药物治疗可怕后果的情况下遭受突发事件。