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Endogenous Sialic Acid-Engineered Micelles: a Multifunctional Platform for On-Demand Methotrexate Delivery and Bone Repair of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) patients have suffered from current drug therapeutic regimen for its high toxicity and absent bone regeneration on existing erosion, seriously affecting quality of life. Herein, a sialic acid-Dextran-octadecylic acid (SA-Dex-OA) conjugate was synthesized to form micelles with a 55.06 μg/mL critical micelle concentration. The obtained micelles could encapsulate a disease-modifying anti-rheumatic drug, methotrexate (MTX) with a 4.28 % (w/w) drug content, featuring sustained drug release behavior over 48 h. In vitro and in vivo study showed that SA-Dex-OA micelles significantly improved accumulation and transportation through combination between SA and E-selectin receptors in inflamed cells and arthritic paws highly expressing E-selectin. MTX loaded SA-Dex-OA micelles not only significantly inhibited inflammatory response, but also diminished the adverse effects of MTX, as reflected by reduced alanine aminotransferase, aspartate aminotransferase, creatinine and urea nitrogen levels. Most importantly, the bone mineral density in rats treated with MTX loaded SA-Dex-OA micelles was significantly higher than that of free MTX and Dex-OA/MTX micelles (increasing from 391.4, 417.4 to 492.7 mg/cc), benefiting from the effects of endogenous sialic acid on promoting MC3T3-E1 cell differentiation and mineralization. It is anticipated that SA-based micelles with bone repair activities have great potential for RA treatment and other metabolic bone diseases with serious bone erosion.

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Publication details

The article was received on 13 Nov 2017, accepted on 09 Jan 2018 and first published on 10 Jan 2018


Article type: Paper
DOI: 10.1039/C7NR08430G
Citation: Nanoscale, 2018, Accepted Manuscript
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    Endogenous Sialic Acid-Engineered Micelles: a Multifunctional Platform for On-Demand Methotrexate Delivery and Bone Repair of Rheumatoid Arthritis

    X. Xu, W. Li, X. Wang, Y. Du, X. Kang, J. Hu, S. Li, X. Ying, J. You and Y. Du, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C7NR08430G

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