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Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.

Publication ,  Journal Article
Mwangi, TK; Berke, IM; Nieves, EH; Bell, RD; Adams, SB; Setton, LA
Published in: J Control Release
August 10, 2018

OBJECTIVE: Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. DESIGN: Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. RESULTS: Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. CONCLUSION: Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a thickening of synovium for joints with induced arthritis, and support the concept that intra-articular drug delivery effectiveness may vary with the state of joint pathology.

Duke Scholars

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Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

August 10, 2018

Volume

283

Start / End Page

76 / 83

Location

Netherlands

Related Subject Headings

  • Synovial Membrane
  • Rats, Sprague-Dawley
  • Pharmacology & Pharmacy
  • Osteoarthritis
  • Male
  • Lymph Nodes
  • Knee Joint
  • Joint Instability
  • Injections, Intra-Articular
  • Dextrans
 

Citation

APA
Chicago
ICMJE
MLA
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Mwangi, T. K., Berke, I. M., Nieves, E. H., Bell, R. D., Adams, S. B., & Setton, L. A. (2018). Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints. J Control Release, 283, 76–83. https://doi.org/10.1016/j.jconrel.2018.05.029
Mwangi, Timothy K., Ian M. Berke, Eduardo H. Nieves, Richard D. Bell, Samuel B. Adams, and Lori A. Setton. “Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.J Control Release 283 (August 10, 2018): 76–83. https://doi.org/10.1016/j.jconrel.2018.05.029.
Mwangi TK, Berke IM, Nieves EH, Bell RD, Adams SB, Setton LA. Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints. J Control Release. 2018 Aug 10;283:76–83.
Mwangi, Timothy K., et al. “Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.J Control Release, vol. 283, Aug. 2018, pp. 76–83. Pubmed, doi:10.1016/j.jconrel.2018.05.029.
Mwangi TK, Berke IM, Nieves EH, Bell RD, Adams SB, Setton LA. Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints. J Control Release. 2018 Aug 10;283:76–83.
Journal cover image

Published In

J Control Release

DOI

EISSN

1873-4995

Publication Date

August 10, 2018

Volume

283

Start / End Page

76 / 83

Location

Netherlands

Related Subject Headings

  • Synovial Membrane
  • Rats, Sprague-Dawley
  • Pharmacology & Pharmacy
  • Osteoarthritis
  • Male
  • Lymph Nodes
  • Knee Joint
  • Joint Instability
  • Injections, Intra-Articular
  • Dextrans