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

摘要 数百万美国人患有关节炎（例如，骨关节炎或OA），一种与炎症相关的疾病， 导致疼痛和残疾，特别是在老年人中。目前的治疗重点是缓解 关节中的疼痛/炎症包括类固醇、非类固醇或非阿片类抗炎药物，以及内- 关节注射然而，这些药物具有局限性和许多副作用，如引起胃溃疡， 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用于治疗OA疼痛的控释药物， 炎症在这项研究中，我们想研究另一种方法来管理OA疼痛，通过内， 一种新型离子液体水凝胶的关节注射。透明质酸（HA）关节内注射是常用的 由于其独特的抑制抗炎和软骨保护的能力，用于临床治疗关节疼痛。 此外，当HA与其他止痛药物（例如，地塞米松或DEX），新的 组合具有比单独HA更大的疼痛缓解功效。 近年来，离子液体和低共熔溶剂由于其高稳定性和高稳定性， 更高的载药量。该液体还改善药物组织渗透，并可作为 药物本身（如利多卡因）。我们假设透明质酸接枝离子液体/深共熔 溶剂（例如，癸酸-利多卡因）将增加治疗OA疼痛和炎症的疗效 同时在体外和体内均防止连接变性。在这笔追加补助金中，我们将 代表性不足的研究生Tra Vinikoor通过使用HA移植的离子 液体或低共熔溶剂，具有预防关节退变和减轻炎症的双重作用。 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）。这项研究将是非常重要的学生继续她的工作 可注射水凝胶用于软骨再生/OA治疗，并为她实现她的目标奠定了坚实的基础。 学术界的长期职业目标。

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.