An In Situ Depot for Continuous Evolution of Gaseous H 2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis

Angew Chem Int Ed Engl. 2018 Jul 26;57(31):9875-9879. doi: 10.1002/anie.201806159. Epub 2018 Jul 6.

Abstract

Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2 ) is known to have anti-inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes.

Keywords: hydrogen gas; magnesium; medical gas; osteoarthritis; tissue inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Hydrogen / chemistry*
  • Magnesium / chemistry
  • Magnesium / therapeutic use*
  • Mice
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / therapeutic use*
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / therapeutic use*
  • RAW 264.7 Cells
  • Surface Properties

Substances

  • Organometallic Compounds
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Hydrogen
  • Magnesium