治疗各种炎症和预防排斥反应时，地塞米松是疗效最好应用最广的一线药物。地塞米松可诱发骨质疏松症和血栓症，限制了它的应用，目前没法克服。我国不仅生产全球90%地塞米松，也是地塞米松应用大国。克服两种副反应对国家有实际贡献。申请人曾用抗血栓RGD-四肽共价缀合地塞米松形成纳米药物，克服了两种副反应，只是未确认靶向性。本课题拟以Lys为桥将抗血栓RGD-四肽和增强免疫抑制的尿毒素三肽生成6种八肽与地塞米松共价构建靶向递送体系5a-f。以体系5a为代表的前期评价显示，5a抗炎和延长心肌存活的最低有效剂量分别是地塞米松的1/850和1/25，远优于RGD-四肽与地塞米松的缀合物，确认靶向递送体系可行。本课题拟制备5a-f、评价活性和副反应、揭露炎症靶向。实施本课题，既可为患者提供疗效好毒副作用小的靶向递送地塞米松的纳米体系，又可稳定我国生产地塞米松的大国地位。 因而具有科学意义、临床意义和经济价值

Dex is the most effective anti-inflammatory glucocorticoid in treating chronic inflammation, acute inflammation, peritoneal adhesion, cardio-pulmonary bypass, acute infection, rheumatoid arthritis, primary immune thrombocytopenia, perioperative immuno¬suppression of cardiac transplantation and rejection of the transplanted organ. However, the clinical efficacy of Dex is limited by osteoporosis and thrombosis, the most serious side effects. Recently, anti-adhesion RGDS, RGDV and RGDF were covalently conjugated with Dex, prepared three nano-medicines to the mentioned side effects. However, the inflammatory targeting of the conjugates remains to be elucidated. This project will covalently conjugate Dex with Lys(Arg- Gly-Asp-Val)Glu-Asp-Gly, Lys(Arg-Gly-Asp-Val)His-Gly-Glu, Lys(Arg-Gly-Asp- Val)His-Gly-Glu, Lys(Arg-Gly-Asp-Phe)Glu-Asp-Gly, Lys(Arg-Gly-Asp-Phe)His- Gly-Glu and Lys(Arg-Gly-Asp-Phe)His-Gly-Glu to construct 6 delivery systems, 5a-f, of inflammatory targeting. To limit investigation risk, this project prepared a delivery system 5a and evaluated its activities in inhibiting inflammation and prolonging cardiac muscle living time. It was found that the minimal effective dose of 5a in inhibiting inflammation and prolonging cardiac muscle living time are 1/850 and 1/25 of that of Dex, respectively. By preparing delivery system 5a-f, evaluating therapeutic actions and side reactions, and exploring inflammatory targeting this project will able to provide targeting delivery system of Dex with high efficacy and low side reaction for clinical therapy of Dex.