Macrophage-Targeted Dextran Sulfate-Dexamethasone Conjugate Micelles for Effective Treatment of Rheumatoid Arthritis
Jiangfan Han,
Ren Na,
Ningning Zhao,
Xiaofeng Yuan,
Linke Fu,
Jianmei Jing,
Airong Qian,
Weiliang Ye
Affiliations
Jiangfan Han
Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
Ren Na
Department of Epidemiology and Health Statistics, Faculty of Military Preventive Medicine, Fourth Military Medical University, Xi’an 710032, China
Ningning Zhao
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China
Xiaofeng Yuan
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China
Linke Fu
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China
Jianmei Jing
Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710038, China
Airong Qian
Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China
Weiliang Ye
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China
Rheumatoid arthritis (RA) is a chronic, systemic immune disease that causes joint affection and even disability. Activated macrophages play an important role in the pathogenesis and progression of RA by producing pro-inflammatory factors. The use of dexamethasone (DXM) is effective in relieving the intractable pain and inflammatory progression of RA. However, long-term use of DXM is strongly associated with increased rates of diabetes, osteoporosis, bone fractures, and mortality, which hinders its clinical use. In this study, the dextran sulfate-cisaconitic anhydride-dexamethasone (DXM@DS-cad-DXM) micelles were prepared to treat RA by selectively recognizing scavenger receptor (SR) on the activated macrophages. The potent targeting property of DXM@DS-cad-DXM micelles to SR was by fluorescence microscope. Additionally, the effective accumulation and powerful anti-inflammatory activity of DXM@DS-cad-DXM micelles were observed in the inflamed joints of adjuvant-induced arthritis (AIA) rats after intravenous administration. Overall, DXM@DS-cad-DXM micelles are a potentially effective nanomedicine for targeted therapy of RA.
