Nanotherapy in Joints: Increasing Endogenous Hyaluronan Production by Delivering Hyaluronan Synthase 2

Adv Mater. 2019 Nov;31(46):e1904535. doi: 10.1002/adma.201904535. Epub 2019 Sep 24.

Abstract

Osteoarthritis (OA) is a common joint degenerative disease that causes pain, joint damage, and dysfunction. External hyaluronic acid (HA) supplement is a common method for the management of osteoarthritis which requires multi-injections. It is demonstrated that biodegradable mesoporous silica nanoparticles successfully deliver an enzyme, hyaluronan synthase type 2 (HAS2), into synoviocytes from the temporomandibular joint (TMJ) and generate endogenous HA with high molecular weights. In a rat TMJ osteoarthritis inflammation model, this strategy promotes endogenous HA production and inhibits the synovial inflammation of OA for more than 3 weeks with one-shot administration. Such nanotherapy also helps repairing the bone defects in a rat OA bone defect model.

Keywords: drug carriers; hyaluronic acid; nanoparticles; osteoarthritis; protein delivery.

MeSH terms

  • Animals
  • Cell Line
  • Humans
  • Hyaluronan Synthases / chemistry
  • Hyaluronan Synthases / metabolism
  • Hyaluronan Synthases / pharmacology*
  • Hyaluronan Synthases / therapeutic use
  • Hyaluronic Acid / biosynthesis*
  • Hyaluronic Acid / chemistry
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Joints / drug effects*
  • Joints / metabolism*
  • Molecular Weight
  • Nanomedicine / methods*
  • Nanoparticles / chemistry
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Porosity
  • Rats
  • Silicon Dioxide / chemistry
  • Synoviocytes / drug effects
  • Synoviocytes / metabolism
  • Synoviocytes / pathology

Substances

  • Silicon Dioxide
  • Hyaluronic Acid
  • Hyaluronan Synthases