溶致液晶关节腔递药系统及其对关节保护机制的研究

Osteoarthritis is a chronic disease which would cause progressive degeneration of articular cartilage. The keys to the osteoarthritis treatment are articulation protection and pain mitigation. However, the universal therapy, based on the intra-articular administration of analgesic drugs, is just alleviation of arthralgia rather than effective articulation protection. This phenomenon might be attributed to lacking of drug carrier with flexibility and responsiveness. Our previous study revealed that the lyotropic liquid crystal (LLC) has spring-like effect and rearrangement ability according to articulation motion, which could protect the articular cartilage from sudden shock and decompose the lateral stress of the articulation. Though the LLC-based drug delivery system offers good cushioning and protection capability, the protection mechanism is still ambiguous regarding of the dependence of their corresponding articulation protection effects on the various crystal cell architectures. In this study, a novel LLC system with diverse crystal cell architectures was applied for intra-articular drug delivery for both articulation protection and pain mitigation in the osteoarthritis treatment. To investigate its protection effect on the impaired articulation of the osteoarthritis patients, the muscle-bone model in combination with the articulation biomechanical properties and finite element calculation is constructed. Additionally, a mesoscopic dynamics simulation system is established to comprehensively elucidate the articulation protection mechanism of the LLC-based intra-articular drug delivery system. These potentially promising findings will significantly contribute to the development of functional intra-articular drug delivery system for osteoarthritis treatment where both articulation protection and prevention of articular cartilage degeneration are of great importance.

骨关节炎是以关节软骨磨损退变为特征的慢性疾病，其关键治疗目标是保护关节和缓解关节肿痛症状。临床常用疗法是关节腔注射镇痛药物制剂，但只能缓解肿痛症状，无法有效保护关节，这主要归因于缺乏具有弹性和能响应关节运动的关节腔递药系统。本课题组研究发现，溶致液晶的晶格单元具有类弹簧效应，能缓冲关节受到的冲击震荡，保护关节；同时能响应关节运动重排晶格，分解关节应力，减小应力强度，减轻关节磨损。前期研究结果表明，液晶递药系统兼具保护关节和缓释药物的作用。但溶致液晶晶格结构复杂，不同晶格结构的液晶体系对关节的保护功效缺乏系统研究，且作用机制尚不明确。本课题创新性地将溶致液晶系统应用于关节腔药物递送，构建生物力学特性与有限元分析相结合的肌骨模型以探究晶格结构对关节的保护功效，建立介观模拟方法同步研究晶格结构对关节运动的响应行为，阐明溶致液晶递药系统的关节保护机制，为功能性关节腔递药系统的研发提供指导意义。

骨关节炎是以关节软骨磨损退变为特征的慢性疾病，其关键治疗目标是保护关节和缓解关节肿痛症状。然而现有临床疗法，如关节腔注射镇痛药物，只能缓解肿痛症状，无法有效保护关节。本项目利用溶致液晶独特可控的晶格结构，致力于构建具有适宜弹性且能响应关节运动的关节腔递药系统。本项目研究结果表明，通过调控溶致液晶基质及其助溶剂的类型和比例，可构建具有不同晶格结构的液晶前体和液晶凝胶，其晶格结构可包载并缓释药物。通过建立关节运动的力学模型、构建生物力学特性与有限元分析相结合的肌骨模型等手段，揭示了关节运动与液晶晶格结构变化的相关性和不同晶格结构的溶致液晶保护关节作用机制：溶致液晶的晶格单元具有类弹簧效应，能缓冲关节受到的冲击震荡，保护关节；同时能响应关节运动重排晶格，分解关节应力，减小应力强度，减轻关节磨损。药效学评价结果表明，液晶递药系统兼具保护关节和缓解关节肿痛的作用，是一个较为理想的关节腔递药系统。本项目的实施，对新型功能性关节腔递药系统的研发具有一定的指导意义。