基于羟基磷灰石和壳寡糖的纳米递药系统的类风湿关节炎的靶向治疗及骨再生研究

Impaired joint function induced by long-term inflammation infiltration is mainly responsible for poor prognosis of rheumatoid arthritis (RA). RA patients have suffered from current drug therapeutic regimen for its serious adverse effects, low efficacy and absent bone regeneration on existing erosion. Targeting Drug Delivery System (TDDS) is a promising mean to treat RA safely and efficiently. On the basis of previous study on TDDS for RA treatment, sialic acid modified chitosan/hydroxyapatite nano drug delivery system was constructed. A specific combination between sialic acid and E-selectin highly expressed in vascular endothelial cells of inflamed paws contributes to an improved accumulation in arthritic paws; low pH value in inflamed paws and cells leads to rapid degradation of hydroxyapatite and triggered drug release, thus, inflammatory response can be inhibited accompanied by minor adverse effects; Moreover, the residual chitosan oligosaccharide can play a role in promoting cartilage renovation by enhancing synthesis of endogenous substances including glycosaminoglycan; Sialic acid and hydroxyapatite can exert bone repair and regeneration by means of improvement in rapid mineralization of osteoblast. Cooperated with anti-inflammatory efficacy of drugs, it may demonstrate synergistic therapy of RA, providing novel idea and approach for an efficient RA treatment.

长期炎症浸润造成关节功能受损是导致类风湿关节炎患者预后差的主要原因。现有的药物治疗存在着毒副作用大、疗效差、对骨修复作用缺失的问题，药物的靶向治疗有望成为解决上述问题的有效手段。本项目拟在前期针对关节炎的靶向药物治疗的基础上，构建唾液酸修饰壳寡糖/羟基磷灰石纳米给药系统，通过唾液酸与关节炎部位血管内皮细胞表面高表达的E选择素的特异性结合，实现关节炎的高度靶向和蓄积；响应关节炎症部位和细胞内的低pH，通过羟基磷灰石的快速降解，迅速释放出药物，显著抑制炎症反应，降低药物的毒副作用；同时，残留的壳寡糖可促进软骨细胞合成糖胺多糖等内源性物质，发挥促软骨修复作用，唾液酸和羟基磷灰石可促进成骨细胞快速矿化，发挥骨修复与再生作用，与药物的抗炎疗效协同作用，实现类风湿关节炎的安全高效治疗，为其临床治疗提供新思路、新方法。

长期炎症浸润造成关节功能受损是导致类风湿关节炎患者预后差的主要原因。现有的药物治疗存在着毒副作用大、疗效差、对骨修复作用缺失的问题，药物的靶向治疗有望成为解决上述问题的有效手段。本项目拟在前期针对关节炎的靶向药物治疗的基础上，构建唾液酸修饰壳寡糖/羟基磷灰石纳米给药系统，通过唾液酸与关节炎部位血管内皮细胞表面高表达的E选择素的特异性结合，实现关节炎的高度靶向和蓄积；响应关节炎症部位和细胞内的低pH，通过羟基磷灰石的快速降解，迅速释放出药物，显著抑制炎症反应，降低药物的毒副作用；同时，残留的壳寡糖可促进软骨细胞合成糖胺多糖等内源性物质，发挥促软骨修复作用，唾液酸和羟基磷灰石可促进成骨细胞快速矿化，发挥骨修复与再生作用，与药物的抗炎疗效协同作用，实现类风湿关节炎的安全高效治疗，为其临床治疗提供新思路、新方法。