Characterization of poly(L-glutamic acid)-grafted hyaluronan as a novel candidate medicine and biomedical device for intra-articular injection

J Biomed Mater Res A. 2017 Nov;105(11):3006-3016. doi: 10.1002/jbm.a.36155. Epub 2017 Aug 9.

Abstract

A novel hyaluronan (HA) derivative, poly(L-glutamic acid)-grafted hyaluronan (PGA-g-HA), was synthesized to improve the durability of conventional HA products for intra-articular injection. The purpose of this study was to investigate the characteristics of the novel HA derivative in terms of viscoelasticity, degradation behavior, non-immunogenicity, and bioactivity using preliminary in vitro and in vivo experiments. The storage modulus (G') and loss modulus (G″) of PGA-g-HA were similar to those of HA80 (approximately 8.0 × 105 Da) rather than those of original HA200 (approximately 2.0 × 106 Da). PGA-g-HA showed strong resistance against hyaluronidase hydrolysis compared to unmodified HA200. The immunogenicity resulting from grafting PGA to HA200 was not detected in bone marrow derived dendritic cells. The anti-inflammatory activity of PGA-g-HA was confirmed in IL-1β-stimulated chondrocytes. In addition, compared to unmodified HA200, the intra-articular injection of PGA-g-HA produced greater chondroprotective effects on a monoiodoacetic acid-induced model of rat knee osteoarthritis at two weeks after a single treatment. Therefore, PGA-g-HA is expected to be a promising medicine and biomedical device for intra-articular injection. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3006-3016, 2017.

Keywords: cartilage; hyaluronan; intra-articular injection; poly(L-glutamic acid).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use*
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / immunology
  • Elasticity
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Male
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / immunology
  • Polyglutamic Acid / administration & dosage
  • Polyglutamic Acid / chemistry
  • Polyglutamic Acid / therapeutic use*
  • Rats, Sprague-Dawley
  • Viscosity

Substances

  • Anti-Inflammatory Agents
  • Polyglutamic Acid
  • Hyaluronic Acid