Synthesis of self-assembled IL-1Ra-presenting nanoparticles for the treatment of osteoarthritis.
Osteoarthritis is a progressive joint disease that results in degradation of cartilage in load-bearing joints. Pain and inflammation in the joint are the hallmarks of this condition, which further exacerbate the cartilage destruction and health of the patient. It is hence imperative to treat the joint inflammation at the earliest. Interleukin 1 (IL-1) blockade by IL-1 receptor antagonist (IL-1Ra) has shown promise in the clinic but this therapy suffers from rapid clearance, high doses, and frequent intervention. Use of carrier particles that result in longer residence time has been proposed. Here we have synthesized a new class of nanoparticles presenting IL-1Ra on the surface and with tunable size from 300 to 700 nm. These IL-1Ra-poly(2-hydroxyethyl methacrylate)-pyridine nanoparticles are cytocompatible and stable in serum-containing solutions for several days. Our results further demonstrate that these nanoparticles are capable of blocking IL-1β signaling in an NF-κB inducible reporter cell line. These engineered nanoparticles are promising for localized intra-articular delivery in joint space to reduce inflammation in osteoarthritis and other inflammatory diseases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 595-599, 2016.
Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332.
Rachit
R
Agarwal
Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332.|Materials Engineering Department, Franciscan University Center, Santa Maria, RS 97010-491, Brazil.
Tiago M
TM
Volkmer
Department of Chemistry and Biochemistry, University of South Carolina, ColumbiaSouth Carolina 29208.
Peiyi
P
Wang
A&Q NanoDesigns, LLC, ColumbiaSouth Carolina 29201.
L Andrew
LA
Lee
Department of Chemistry and Biochemistry, University of South Carolina, ColumbiaSouth Carolina 29208.
Qian
Q
Wang
Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332.
Andrés J
AJ
García
D000818:Animals; D000067493:Dynamic Light Scattering; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010003:Osteoarthritis / Q000188:drug therapy*; D010316:Particle Size; D000067996:RAW 264.7 Cells
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D008689:Methacrylates; D016328:NF-kappa B; C005044:hydroxyethyl methacrylate
biomaterials; cytokine; immunomodulation; polymeric particles; protein delivery