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.

摘要 数以百万计的美国人患有关节炎(如骨关节炎或骨关节炎)，这是一种与炎症有关的疾病， 会导致疼痛和残疾，尤其是在老年人中。目前的治疗方法侧重于缓解 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。然而，这些药物有局限性，也有许多副作用，如引起胃病。 口服时会出血/溃疡。在家长资助中，我们提出了一种使用非阿片类止痛药的方法 微针技术获得的药物控释治疗骨性关节炎疼痛和疼痛 发炎。在这项研究中，我们想要研究另一种方法来管理骨性关节炎疼痛通过内部 关节注射一种新型离子液体水凝胶。透明质酸(HA)关节内注射是常用的 由于其独特的抗炎和保护软骨的能力，临床上治疗关节疼痛。 此外，当HA与其他止痛药(如地塞米松或地塞米松)协同作用时，新的 联合用药比单独使用HA有更好的止痛效果。 近年来，离子液体和深共晶溶剂因其高度的稳定性和稳定性而备受关注。 更高载药量的有效性。这种液体还可以促进药物组织的渗透，并可以起到 药物本身(例如利多卡因)。我们的假设是透明质酸接枝了离子液体/深共晶 溶剂(例如，癸酸-利多卡因)将提高治疗骨性关节炎疼痛和炎症的疗效 同时防止在体外和体内的联合退化。在这笔补充拨款中，我们将拥有我们的 未被充分代表的研究生，Tra Vinikoor，通过使用HA嫁接的离子材料来研究和改进OA治疗 液体或深共晶溶剂，具有防止关节退变和消炎的双重功能。 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(卡托·劳伦辛博士)。这项研究将对学生继续她的工作非常重要 可注射水凝胶用于软骨再生/骨关节炎治疗，并为她实现她的目标奠定坚实的基础 在学术界的长期职业目标。