title: Direct chemotherapeutic dual drug delivery through intra-articular injection for synergistic enhancement of rheumatoid arthritis treatment.
abstract: 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.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: A
authors.initials: A
authors.lastname: Reum Son
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Da Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Seung
authors.initials: S
authors.lastname: Hun Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Ja
authors.initials: J
authors.lastname: Yong Jang
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Kyungsook
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Byoung
authors.initials: B
authors.lastname: Ju Kim
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon 443-759, Korea.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yun Yin
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Jae
authors.initials: J
authors.lastname: Ho Kim
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.|Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon 443-759, Korea.
authors.forename: Byoung
authors.initials: B
authors.lastname: Hyun Min
authors.affiliation: Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 130-650, Korea.
authors.forename: Dong
authors.initials: D
authors.lastname: Keun Han
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea.
authors.forename: Moon
authors.initials: M
authors.lastname: Suk Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D051381:Rats; D019265:Spectroscopy, Near-Infrared; D055114:X-Ray Microtomography
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D015415:Biomarkers; D003907:Dexamethasone; D008727:Methotrexate