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Open Access Research article

Magnetically retainable microparticles for drug delivery to the joint: efficacy studies in an antigen-induced arthritis model in mice

Nicoleta Butoescu1, Christian A Seemayer2, Gaby Palmer34, Pierre-André Guerne34, Cem Gabay34, Eric Doelker1 and Olivier Jordan1*

Author Affiliations

1 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland

2 Division of Pathology and Immunology, University Hospital of Geneva, Rue Michel-Servet 1, 1206 Geneva, Switzerland

3 Division of Rheumatology, Department of Internal Medicine, University Hospital, Avenue Beau-Séjour 26, 1206 Geneva, Switzerland

4 Department of Pathology and Immunology, University of Geneva School of Medicine, Rue Michel-Servet 1, 1206 Geneva, Switzerland

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Arthritis Research & Therapy 2009, 11:R72  doi:10.1186/ar2701

Published: 19 May 2009

Abstract

Introduction

Conventional corticosteroid suspensions for the intra-articular treatment of arthritis suffer from limitations such as crystal formation or rapid clearance from the joint. The purpose of this study was to investigate an innovative alternative consisting of corticosteroid encapsulation into magnetically retainable microparticles.

Methods

Microparticles (1 or 10 μm) containing both superparamagnetic iron oxide nanoparticles (SPIONs) and dexamethasone 21-acetate (DXM) were prepared. In a preliminary study, we compared the persistence of microparticles of both sizes in the joint. A second study evaluated the influence of a subcutaneously implanted magnet near the knee on the retention of magnetic microparticles in the joint by in vivo imaging. Finally, the efficacy of 10-μm microparticles was investigated using a model of antigen-induced arthritis (AIA) in mice. Phosphate-buffered saline, DXM suspension, SPION suspension, blank microparticles and microparticles containing only SPIONs were used as controls. Arthritis severity was assessed using 99mTc accumulation and histological scoring.

Results

Due to their capacity of encapsulating more corticosteroid and their increased joint retention, the 10-μm microparticles were more suitable vectors than the 1-μm microparticles for corticosteroid delivery to the joint. The presence of a magnet resulted in higher magnetic retention in the joint, as demonstrated by a higher fluorescence signal. The therapeutic efficacy in AIA of 10-μm microparticles containing DXM and SPIONs was similar to that of the DXM suspension, proving that the bioactive agent is released. Moreover, the anti-inflammatory effect of DXM-containing microparticles was more important than that of blank microparticles or microparticles containing only SPIONs. The presence of a magnet did not induce a greater inflammatory reaction.

Conclusions

This study confirms the effectiveness of an innovative approach of using magnetically retainable microparticles as intra-articular drug delivery systems. A major advantage comes from a versatile polymer matrix, which allows the encapsulation of many classes of therapeutic agents (for example, p38 mitogen-activated protein kinase inhibitors), which may reduce systemic side effects.