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 数百万美国人患有关节炎（例如骨关节炎或 OA），这是一种与炎症相关的疾病， 导致疼痛和残疾，尤其是老年人群。目前的治疗重点是缓解 关节疼痛/炎症包括类固醇、非类固醇或非阿片类抗炎药，以及 关节注射。但这些药物都有其局限性，并且副作用较多，如引起胃病等。 口服时出血/溃疡。在家长资助中，我们提出了一种使用非阿片类镇痛药的方法 通过微针技术获得的可控缓释药物，用于治疗骨关节炎疼痛 炎。在这项研究中，我们想研究另一种通过内部治疗来控制骨关节炎疼痛的方法。 新型离子液体水凝胶的关节注射。常用的有透明质酸（HA）关节内注射 由于其独特的抑制抗炎和软骨保护能力，在临床上治疗关节疼痛。 此外，当 HA 与其他止痛药物（例如地塞米松或 DEX）协同作用时，新的止痛药物 联合使用比单独使用HA具有更好的止痛效果。 近年来，离子液体和低共熔溶剂因其高稳定性和低共熔性而受到广泛关注。 更高载药量的有效性。该液体还可以提高药物的组织渗透性，并可充当 药物本身（例如利多卡因）。我们的假设是透明质酸接枝离子液体/深度共晶 溶剂（例如癸酸-利多卡因）可增强治疗 OA 疼痛和炎症的疗效 同时在体外和体内防止连接变性。在这笔补充赠款中，我们将拥有 代表性不足的研究生 Tra Vinikoor 通过使用 HA 接枝离子来研究和改进 OA 治疗 液体或低共熔溶剂，具有防止关节退变和减轻炎症的双重功能。 研究生将在 PI（Thanh Nguyen 博士）的支持和监督下进行研究 共同导师（Cato Laurencin 博士）。这项研究对于学生继续她的工作非常重要 用于软骨再生/骨关节炎治疗的注射水凝胶，为她实现梦想奠定了坚实的基础 学术界的长期职业目标。