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

• 批准号: 10852320
• 负责人: Lakshmi S Nair
• 金额: $ 7.14万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 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/10852320
• 关键词: Absence of pain sensation; Acute; Address; Adrenal Cortex Hormones; American; Analgesics; Anesthetics; Animal Model; Anti-Inflammatory Agents; Attention; Attenuated; Behavioral; Biocompatible Materials; CCL4 gene; Cell Line; Cells; Cessation of life; Clinical; Clinical Data; Combined Modality Therapy; 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; Knee; LOX gene; Ligation; Lipids; Local Anesthetics; Low Back Pain; Macrophage; Mechanics; Mediator; Methylprednisolone; Modeling; Musculoskeletal; Musculoskeletal Pain; Musculoskeletal System; Nerve; Nerve Block; Neuralgia; Neuroglia; Neurons; Nociception; Operative Surgical Procedures; Opiate Addiction; Opioid; Opioid Rotation; Oral; Overdose; Pain; Pain intensity; Pain management; Patients; Pharmaceutical Preparations; Postoperative Period; Process; Proliferating; Property; Quality of life; Rattus; Research; Resolution; Schwann Cells; Shoulder; Signal Transduction; Site; Spinal Ganglia; Testing; United States; analog; attenuation; behavioral response; clinical pain; compliance behavior; controlled release; efficacy evaluation; experience; improved; in vitro Model; in vivo; in vivo Model; inhibitor; laurencin; lipoxin A4; mechanical allodynia; nanocapsule; nanocomposite; neuroprotection; neurotoxicity; novel; opioid abuse; opioid therapy; opioid use; outpatient facility; pain model; pain relief; painful neuropathy; perineural; pre-clinical; prescription opioid; prevent; response; ropivacaine; safety assessment; sciatic nerve; side effect; synergism

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爆发（即术后痛觉过敏，骨关节炎，枕神经痛， 下背部疼痛）是疼痛强度的增加。目前，处方阿片类药物以治疗这些耀斑 - 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。过量，虐待， 在美国，转移和处方阿片类药物的死亡已经达到流行病。 相关的医疗保健费用超过7000亿美元。我们的长期目标是开发替代性，非依恋性 治疗肌肉骨骼条件的爆发的干预措施。我们提出的研究旨在开发注射剂 通过将局部麻醉与低剂量的抗炎/镇痛作用结合使用长效麻醉制剂 疼痛调节剂和使用工程载体持续递送这些药物。初步研究表明 协同药物组合与注射水凝胶/脂质纳米胶囊的潜力 纳米复合材料延长局部镇痛。我们建议评估临床使用的皮质类固醇以及 新兴的镇痛疼痛调节剂与ropivacaine结合使用，以鉴定协同的药物组合。 将研究扩散和退化控制的释放过程，以持续交付 镇痛疼痛调节剂可预防周围炎症和神经毒性。体内评估 配方的功效和安全性将通过遵循行为和电生理学来执行 大鼠模型中的响应。可注射的长效配方，可以在门诊设施中进行管理 并可以维持7-14天的局部降压作用，将显着提高人们的生活质量 患有阿片类药物治疗的可怕后果的爆发。

项目成果

Perineural local anesthetic treatments for osteoarthritic pain.

• DOI: 10.1007/s40883-021-00223-0
• 发表时间: 2021-09
• 期刊: REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE
• 影响因子: 2.6
• 作者: Knight, Brittany;Walker, Joseph;Nair, Lakshmi S
• 通讯作者: Nair, Lakshmi S

Hair Follicle Stem Cells for Tissue Regeneration.

• DOI: 10.1089/ten.teb.2021.0098
• 发表时间: 2021-07
• 期刊: Tissue engineering. Part B, Reviews
• 作者: Alyssa Peterson;Lakshmi R Nair

Poly(cannabinoid)s: Hemp-Derived Biocompatible Thermoplastic Polyesters with Inherent Antioxidant Properties.

• DOI: 10.1021/acsami.2c05556
• 发表时间: 2022-09-28
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Daniels, Robert;Morato, Erick Orozco;Yassin, Omer A.;Mao, Jiahao;Mutlu, Zeynep;Jain, Mayank;Valenti, Joseph;Cakmak, Mukerrem;Nair, Lakshmi S.;Sotzing, Gregory A.
• 通讯作者: Sotzing, Gregory A.