Single-administration microneedles with controlled sustained release of non-opioid analgesics to treat osteoarthritis pain

单次给药微针控制缓释非阿片类镇痛药治疗骨关节炎疼痛

• 批准号: 10721752
• 负责人: Thanh Nguyen
• 金额: $ 8.31万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-05 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10721752
• 关键词: Academia; Acids; American; Analgesics; Arthralgia; Arthritis; Attention; Cartilage; Clinical; Degenerative polyarthritis; Dexamethasone; Disease; Effectiveness; Foundations; Goals; Grant; Hemorrhage; Hyaluronic Acid; Hydrogels; In Vitro; Inflammation; Injectable; Intra-Articular Injections; Joints; Lidocaine; Liquid substance; Mentors; Natural regeneration; Needles; Oral; Pain; Penetration; Pharmaceutical Preparations; Population; Research; Solvents; Steroids; Stomach; Students; Supervision; Techniques; Therapeutic Effect; Tissues; Ulcer; Underrepresented Students; Work; arthropathies; career; cartilage degradation; cartilage regeneration; chondroprotection; design; disability; graduate student; improved; in vivo; joint destruction; laurencin; non-opioid analgesic; novel; osteoarthritis pain; pain relief; parent grant; prevent; side effect; synergism

Abstract Millions of Americans suffer from arthritis (e.g., osteoarthritis or OA), a disease associated with inflammation that causes pain and disability, especially in senior population. Current treatments that focus on alleviating pain/inflammation in joints include steroids, non-steroid or non-opioids anti-inflammation drugs, and intra- articular injection. However, these drugs have limitations and many side effects such as causing stomach bleeding/ ulcers when taken orally. In the parent grant, we proposed an approach to use non-opioid analgesic drugs with controlled sustain release obtained from microneedle technique for the treatment of OA pain and inflammation. In this study, we would like to investigate another approach to manage OA pain through intra- articular injection of a novel ionic liquid hydrogel. Hyaluronic acid (HA) intra-articular injection is commonly used to clinically treat joint pain due to its unique ability to suppress anti-inflammation and chondroprotection. Furthermore, when HA synergizes with other pain-relief drugs (e.g., Dexamethasone or DEX), the new combination has a greater pain relief efficacy than HA alone. Recently ionic liquid and deep eutectic solvents have gained a great attention because of their high stability and effectiveness for higher drug loading capacity. The liquid also improves drug tissue penetration and can act as drugs themselves (e.g. lidocaine). Our hypothesis is that hyaluronic acid grafted ionic liquid/ deep eutectic solvents (e.g., Decanoic Acid-Lidocaine) would increase therapeutic effect to treat OA pain and inflammation while preventing join degeneration both in vitro and in vivo. In this supplementary grant, we would have our under-represented graduate student, Tra Vinikoor, research and improve OA therapy by using a HA-grafted ionic liquid or deep eutectic solvent with dual functions of preventing joint degeneration and reducing inflammation. The graduate student will perform the study under the support and supervision of the PI (Dr. Thanh Nguyen) and the co-mentor (Dr. Cato Laurencin). This study will be very important to the student to continue her work on injectable hydrogels for cartilage regeneration/OA treatment and lay a strong foundation for her to achieve her long-term career goals in academia.

抽象的 数以百万计的美国人患有关节炎（例如骨关节炎或OA），这种疾病与炎症有关 引起疼痛和残疾，尤其是在老年人中。目前专注于减轻的治疗 关节中的疼痛/炎症包括类固醇，非类固醇或非阿片类药物抗炎药，以及内部 关节注射。但是，这些药物有局限性和许多副作用，例如引起胃 口服时出血/溃疡。在父母赠款中，我们提出了一种使用非阿片类镇痛药的方法 从微针技术获得的具有控制的维持释放的药物，用于治疗OA疼痛和 炎。在这项研究中，我们想调查另一种通过内部管理OA疼痛的方法 新型离子液体水凝胶的关节注射。通常使用透明质酸（HA）关节内注射 由于其独特的抑制抗炎和软骨保护的能力，因此可以在临床上治疗关节疼痛。 此外，当HA与其他止痛药协同（例如，地塞米松或dex）时，新的 组合比单独的HA具有更大的缓解疼痛功效。 最近，由于它们的稳定性高和 较高药物加载能力的有效性。液体还改善了药物组织的渗透，可以充当 毒品本身（例如利多卡因）。我们的假设是透明质酸接枝的离子液体/深晶 溶剂（例如，二烷酸 - 苯甲酸）将增加治疗作用以治疗OA疼痛和炎症 在防止体外和体内结合变性的同时。在这项补充赠款中，我们将拥有我们的 通过使用HA-GRAFT IONIC 液体或深层溶剂，具有预防关节变性和减少炎症的双重功能。 研究生将在PI的支持和监督下进行研究（Thanh Nguyen博士）和 联合学（Cato Laurencin博士）。这项研究对学生继续她的工作非常重要 用于软骨再生/OA处理的可注射水凝胶，为她奠定了坚实的基础 学术界的长期职业目标。