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Journal of Electronic Materials

, Volume 48, Issue 10, pp 6570–6582 | Cite as

An Agarose–Curdlan Nanogel that Carries Etanercept to Target and Neutralises TNF-α Produced by Dectin-1-Expressing Immune Cells

  • Dung H. T. Nguyen
  • Ngoc B. Nguyen
  • Linh T. P. Nguyen
  • Ly T. Do
  • Tung T. Nguyen
  • Nam H. Nguyen
  • Sakurai Kazuo
  • Mochizuki Shinichi
  • Kihara Takanori
  • Thang D. Nguyen
  • Anh T. V. Nguyen
  • Huong T. T. PhamEmail author
Article
  • 13 Downloads

Abstract

Etanercept (ETA) has been used as a drug to neutralise tumour necrotic factor alpha (TNF-α) for treatment of rheumatoid arthritis (RA), yet there are limitations concerning its low specific drug targeting and side effects. In this study, agarose–curdlan encapsulating etanercept (ACE) gel was successfully formulated and evenly distributed as nano-particles of 30–100 nm diameter, exhibiting an ETA encapsulation efficiency of 73.8% and an ETA-releasing efficiency of 50% after 52 h. The number of dectin-1-overexpressing macrophage cells, RAW264.7, exposed to ACE that migrated in the Boyden chamber assay was equal to that exposed to either agarose–curdlan or curdlan nanogels, but substantially higher than those exposed to agarose gel and water-soluble ETA by 67 and 141 fold, respectively (p < 0.05), suggesting the targeting effect of curdlan on dectin-1. Enzyme-linked immunosorbent assay revealed that the ETA released from the ACE nanogel could neutralise TNF-α secreted by lipopolysaccharide (LPS)-induced RAW264.7. Moreover, at 24 h and 72 h, the released ETA showed 1.3- to 4.4-fold greater effectiveness, respectively, than water-soluble ETA. This study demonstrates that the ACE nanogel can attract immune cells and slowly release ETA to efficiently neutralise the TNF-α produced by these cells and, thus, could be a promising ETA carrier for targeted RA treatment.

Keywords

Agarose–curdlan nanogel targeted drug delivery TNF-α neutralization etanercept treatment dectin-1-expressing cell rheumatoid arthritis 

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Notes

Acknowledgement

This work was supported by a grant from Vietnam National University, Hanoi to Huong T. T.Pham Under project number KLEPT.16.01. We thank Msc. Phan Thi Kieu Trang from the Faculty of Environmental Engineering, University of Kitakyushu for her kind guidance on setting the drug targeting experiment, and Dr. Pham Bao Yen from the Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Vietnam National University-Hanoi for English correction

Conflict of interest

The authors report no conflict of interest.

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Copyright information

© The Minerals, Metals & Materials Society 2019

Authors and Affiliations

  • Dung H. T. Nguyen
    • 1
  • Ngoc B. Nguyen
    • 1
  • Linh T. P. Nguyen
    • 1
  • Ly T. Do
    • 1
  • Tung T. Nguyen
    • 1
  • Nam H. Nguyen
    • 2
  • Sakurai Kazuo
    • 3
  • Mochizuki Shinichi
    • 3
  • Kihara Takanori
    • 4
  • Thang D. Nguyen
    • 1
  • Anh T. V. Nguyen
    • 1
  • Huong T. T. Pham
    • 1
    Email author
  1. 1.Key Laboratory of Enzyme and Protein TechnologyVNU University of Science, Vietnam National UniversityThanh XuanVietnam
  2. 2.Nano and Energy Research Center, Faculty of PhysicsVNU University of Science, Vietnam National UniversityThanh XuanVietnam
  3. 3.Department of Chemistry and BiochemistryUniversity of KitakyushuKitakyushuJapan
  4. 4.Department of Life and Environment Engineering, Faculty of Environmental EngineeringUniversity of KitakyushuKitakyushuJapan

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