Peptide-targeted liposomal delivery of dexamethasone for arthritis therapy

Nanomedicine (Lond). 2019 Jun;14(11):1455-1469. doi: 10.2217/nnm-2018-0501. Epub 2019 Apr 2.

Abstract

Aim: Rheumatoid arthritis is an autoimmune disease affecting the joints. Antiarthritic drugs are given systemically, thereby exposing various healthy organs to these drugs, resulting in adverse reactions. Accordingly, there is an urgent need for targeted drug delivery methods for inflamed joints. Materials & methods: We developed a liposomal drug delivery system using a novel peptide ligand (CKPFDRALC) named ART-2, which homes to the inflamed joints when injected intravenously to rats with adjuvant-induced arthritis. Results: The ART-2-coated liposomes encapsulating an antiarthritic drug, dexamethasone (DEX), were more effective in inhibiting arthritis progression than control-DEX liposomes or free DEX, despite a comparable safety profile. Conclusion: Peptide-targeted therapy has advantages over conventional drug delivery and can be adapted for rheumatoid arthritis therapy.

Keywords: adjuvant arthritis; arthritis; dexamethasone; endothelial cells; inflammation; liposomes; nanoparticles; peptide; rheumatoid arthritis; targeted delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacokinetics
  • Arthritis, Experimental / drug therapy*
  • Cell Survival
  • Dexamethasone / chemistry*
  • Dexamethasone / pharmacokinetics
  • Drug Compounding / methods
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Joints / metabolism
  • Liposomes / chemistry*
  • Male
  • Molecular Targeted Therapy / methods
  • Peptides / chemistry*
  • Phosphatidylcholines / chemistry
  • Phosphatidylethanolamines / chemistry
  • Rats
  • Rats, Inbred Lew
  • Surface Properties
  • Tissue Distribution

Substances

  • Anti-Inflammatory Agents
  • Liposomes
  • Peptides
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • dioleoyl phosphatidylethanolamine
  • Dexamethasone
  • 1,2-oleoylphosphatidylcholine