Inflammation Research

, Volume 49, Issue 4, pp 155–161

The suppression of rat collagen-induced arthritis and inhibition of macrophage derived mediator release by liposomal methotrexate formulations

  • A. Williams
  • R. Goodfellow
  • N. Topley
  • N. Amos
  • B. Williams

DOI: 10.1007/s000110050575

Cite this article as:
Williams, A., Goodfellow, R., Topley, N. et al. Inflamm. res. (2000) 49: 155. doi:10.1007/s000110050575

Abstract.

Objective and Design: This study was designed to determine whether liposomes are suitable vehicles for the delivery of methotrexate (MTX-γ-DMPE) for arthritis therapy.¶Material or Subjects: Liposomal formulations containing either egg lecithin (EPC), cholesterol (CHOL) and phosphatidic acid (PA) (MTX-EPC) or distearoylphosphatidylcholine (DSPC), CHOL and distearoylphosphatidylethanolamine conjugated to polyethyleneglycol (PEG) (MTX-PEG) were employed. Rat peritoneal macrophages (rPMφ) were used to test the mechanism of action of these liposomes in vitro, whilst, the rat collagen-induced arthritis (CIA) model was used to evaluate the in vivo efficacy of MTX-EPC and MTX-PEG.¶Treatment: In vitro, rPMφ were incubated with liposomal MTX concentrations ranging from 0 to 15 μg/well. In vivo, rats were given 4 daily intravenous injections of liposomal MTX (2.5 mg/Kg).¶Methods: IL-1β and prostaglandin-E2 (PGE2) release from rPMφ were quantified by immunoradiometric assay. Arthritis progression, in vivo, was measured by serial clinical score and hind paw diameter measurements.¶Results: MTX-EPC and MTX-PEG respectively (15 μg of MTX and 0.15 mg of lipid) were powerful inhibitors of both IL-1β (77 ± 2.3%; 79 ± 4.0%) and PGE2 (75.5 ± 4.9%; 68.5 ± 2.3%) release (mean ± SEM % inhibition) from lipopolysaccaride stimulated rPMφ. In vivo, only MTX-EPC exerted an anti-inflammatory effect, clinical score (p < 0.001) and paw diameter (p < 0.001) measurements being significantly lower than in control rats, after 2 days treatment.¶Conclusions: MTX-EPC and MTX-PEG are potent inhibitors of pro-inflammatory mediators in vitro, but liposomes with long circulation times do not appear to have therapeutic potential for treating arthritis in vivo.

Key words: Arthritis — Interleukin-1β— Macrophage — Prostaglandin E2 

Copyright information

© Birkhäuser Verlag, 2000

Authors and Affiliations

  • A. Williams
    • 1
  • R. Goodfellow
    • 1
  • N. Topley
    • 2
  • N. Amos
    • 1
  • B. Williams
    • 1
  1. 1. Rheumatology Research Laboratory, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, UK, Fax +01222 744388, e-mail: wmdasw@cardiff.ac.uk UK
  2. 2.Institute of Nephrology, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, UK UK

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