Direct chemotherapeutic dual drug delivery through intra-articular injection for synergistic enhancement of rheumatoid arthritis treatment.
A Reum Son, Da Yeon Kim, Seung Hun Park, Ja Yong Jang, Kyungsook Kim, Byoung Ju Kim, Xiang Yun Yin, Jae Ho Kim, Byoung Hyun Min, Dong Keun Han, Moon Suk Kim
Author Information
A Reum Son: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Da Yeon Kim: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Seung Hun Park: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Ja Yong Jang: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Kyungsook Kim: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Byoung Ju Kim: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Xiang Yun Yin: Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon 443-759, Korea.
Jae Ho Kim: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Byoung Hyun Min: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
Dong Keun Han: Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 130-650, Korea.
Moon Suk Kim: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
The effectiveness of systemic rheumatoid arthritis (RA) treatments is limited by difficulties in achieving therapeutic doses within articular joints. We evaluated the ability of intra-articular administration of injectable formulations to synergistically enhance repair of RA joints. Methotrexate-loaded hyaluronic acid (Met-HA), dexamethasone-loaded microcapsules (Dex-M), and Dex-M dispersed inside Met-HA were prepared as viscous emulsions and injected into articular joints using a needle to form a drug depot. By near-infrared (NIR) fluorescence imaging, we confirmed the local release of NIR from the depot injected into the articular joint over an extended period. In comparison with the subjects treated with Met-HA or Dex-M alone, subjects treated simultaneously with Met-HA and Dex-M exhibited faster and more significant RA repair. Collectively, these results indicated that the drug depot formed after intra-articular injection of Met-HA/Dex-M induced long-lasting drug release and allowed Met and Dex to effectively act in the articular joint, resulting in enhanced RA repair.
