Hyaluronic acid-conjugated pH-sensitive liposomes for targeted delivery of prednisolone on rheumatoid arthritis therapy

Nanomedicine (Lond). 2018 May;13(9):1037-1049. doi: 10.2217/nnm-2017-0377. Epub 2018 May 23.

Abstract

Aim: The treatment of rheumatoid arthritis remains a challenge as available therapies still entail the risk of deleterious off-target effects. The present study describes hyaluronic acid-conjugated pH-sensitive liposomes as an effective drug delivery-targeting strategy to synovial cells.

Materials & methods: Therapeutic, cytotoxic and targeting potential of developed liposomes were studied in vitro using macrophages and fibroblasts cell lines.

Results & conclusion: Results suggest an enhanced cellular uptake of conjugated liposomes, mainly mediated by caveolae- and clathrin-dependent endocytosis. In vitro release studies demonstrated that prednisolone was preferentially released under acidic conditions mimicking intracellular endosomal compartments. Overall, results revealed that conjugated pH-sensitive liposomes are a promising nanoapproach for the targeted delivery of prednisolone within inflamed synovial cells for rheumatoid arthritis treatment.

Keywords: corticosteroids; fibroblasts; hyaluronic acid; macrophages; pH-responsive liposomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Cell Line
  • Endocytosis / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Hyaluronic Acid / chemistry*
  • Hydrogen-Ion Concentration
  • Liposomes / chemistry*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • Prednisolone / administration & dosage*
  • Prednisolone / chemistry
  • Prednisolone / therapeutic use*
  • RAW 264.7 Cells

Substances

  • Liposomes
  • Hyaluronic Acid
  • Prednisolone