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Liposomal targeting of glucocorticoids to synovial lining cells strongly increases therapeutic benefit in collagen type II arthritis
  1. J M Metselaar1,
  2. W B van den Berg2,
  3. A E M Holthuysen2,
  4. M H M Wauben3,
  5. G Storm1,
  6. P L E M van Lent2
  1. 1Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, The Netherlands
  2. 2Department of Rheumatology, University Hospital Nijmegen, Nijmegen, The Netherlands
  3. 3Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands
  1. Correspondence to:
    Dr P van Lent
    Department of Rheumatology, University Hospital Nijmegen, University Medical Centre 189, Geert Grooteplein 26-28, 6500 HB Nijmegen, The Netherlands;


Objective: To investigate the effect of a single intravenous treatment with glucocorticoids (GC) encapsulated in long-circulating PEG-liposomes on both joint inflammation and cartilage destruction and to investigate the phenomenon of selective homing of these liposomes in the inflamed synovium.

Methods: Mice with collagen type II-induced arthritis (CIA) were intravenously treated with liposomal and free prednisolone phosphate (PLP) a few days after the first signs of the disease. Joint inflammation was scored during 1 week after treatment, after which sections of the knee joints were prepared for assessment of cartilage damage. In addition, arthritic mice were treated with liposomes containing colloidal gold. 24 hours after injection, knee joint sections were prepared in which the location of liposomes was visualised.

Results: Treatment of CIA with 10 mg/kg liposomal PLP resulted in a strong and lasting resolution of joint inflammation. 10 mg/kg free PLP only became slightly effective after repeated daily injections. Although joint inflammation recurred 1 week after treatment with liposomal PLP, knee joint sections prepared at this time indicated that the cartilage damage was still reduced. Localisation of gold labelled liposomes in the inflamed joints was seen in the proximity of blood vessels, in the cellular infiltrate, but mainly in the synovial lining. Unaffected joints did not take up liposomes.

Conclusions: By using the property of long-circulating liposomes to target the synovial lining selectively in inflamed joints, the anti-inflammatory activity of GC can be greatly increased, showing also the beneficial effect of reduced cartilage destruction.

  • collagen-induced arthritis
  • glucocorticoids
  • joint inflammation
  • liposomes
  • targeting
  • CIA, collagen type II-induced arthritis
  • GC, glucocorticoid(s)
  • IV, intravenous
  • MPS, mononuclear phagocyte system
  • PBS, phosphate buffered saline
  • PEG, poly(ethylene glycol)
  • PLP, prednisolone phosphate
  • RA, rheumatoid arthritis
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  • J M Metselaar and G Storm are members of UNYPHAR, a network collaboration between the Universities of Groningen, Leiden, Utrecht and the pharmaceutical company Yamanouchi.

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