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Biomaterials. 2017 Jul;131:15-26. doi: 10.1016/j.biomaterials.2017.03.044. Epub 2017 Mar 26.

Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis.

Author information

1
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.
2
School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
3
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
4
School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
5
Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore 21231, United States.
6
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
7
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
8
School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
9
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: jhpark1@skku.edu.

Abstract

With the aim of developing nanoparticles for targeted delivery of methotrexate (MTX) to inflamed joints in rheumatoid arthritis (RA), an amphiphilic polysaccharide was synthesized by conjugating 5β-cholanic acid to a dextran sulfate (DS) backbone. Due to its amphiphilic nature, the DS derivative self-assembled into spherical nanoparticles (220 nm in diameter) in aqueous conditions. The MTX was effectively loaded into the DS nanoparticles (loading efficiency: 73.0%) by a simple dialysis method. Interestingly, the DS nanoparticles were selectively taken up by activated macrophages, which are responsible for inflammation and joint destruction, via scavenger receptor class A-mediated endocytosis. When systemically administrated into mice with experimental collagen-induced arthritis (CIA), the DS nanoparticles effectively accumulated in inflamed joints (12-fold more than wild type mice (WT)), implying their high targetability to RA tissues. Moreover, the MTX-loaded DS nanoparticles exhibited significantly improved therapeutic efficacy against CIA in mice compared to free MTX alone. Overall, the data presented here indicate that DS nanoparticles are potentially useful nanomedicines for RA imaging and therapy.

KEYWORDS:

Dextran sulfate; Drug delivery; Macrophage; Nanoparticles; Rheumatoid arthritis

[Indexed for MEDLINE]

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