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Delivery of anti-inflammatory peptides from hollow PEGylated poly(NIPAM) nanoparticles reduces inflammation in an ex vivo osteoarthritis model

J Control Release. 2017 Jul 28:258:161-170. doi: 10.1016/j.jconrel.2017.05.008. Epub 2017 May 8.

Abstract

Targeted delivery of anti-inflammatory osteoarthritis treatments have the potential to significantly decrease undesirable systemic side effects and reduce required therapeutic dosage. Here we present a targeted, non-invasive drug delivery system to decrease inflammation in an osteoarthritis model. Hollow thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been synthesized via degradation of a N,N'-bis(acryloyl)cystamine (BAC) cross-linked core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK). The drug-loaded hollow nanoparticles were effective at delivering a therapeutically active dose of KAFAK to bovine cartilage explants, suppressing pro-inflammatory interleukin-6 (IL-6) expression after interleukin-1 beta (IL-1β) stimulation. This thermosensitive hollow nanoparticle system provides an excellent platform for the delivery of peptide therapeutics into highly proteolytic environments such as osteoarthritis.

Keywords: Anti-inflammatory peptides; Inflammation; N-isopropylacrylamide; Osteoarthritis; Thermosensitive polymer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylic Resins / chemistry*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Cattle
  • Cell-Penetrating Peptides / administration & dosage*
  • Cell-Penetrating Peptides / pharmacokinetics
  • Cell-Penetrating Peptides / pharmacology
  • Delayed-Action Preparations / chemistry*
  • Interleukin-1beta / immunology
  • Interleukin-6 / immunology
  • Mice
  • Nanoparticles / chemistry*
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / immunology
  • RAW 264.7 Cells
  • Temperature

Substances

  • Acrylic Resins
  • Anti-Inflammatory Agents
  • Cell-Penetrating Peptides
  • Delayed-Action Preparations
  • Interleukin-1beta
  • Interleukin-6
  • poly-N-isopropylacrylamide