Research paper Dexamethasone-containing biodegradable superparamagnetic microparticles for intra-articular administration: Physicochemical and magnetic properties, in vitro and in vivo drug release Nicoleta Butoescu a, * , Olivier Jordan a , Pierre Burdet b , Pierre Stadelmann b , Alke Petri-Fink c , Heinrich Hofmann c , Eric Doelker a a School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland b CIME, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland c Powder Technology Laboratory, Institute of Materials, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland article info Article history: Received 7 August 2008 Accepted in revised form 2 March 2009 Available online 20 March 2009 Keywords: PLGA microparticles Dexamethasone acetate Superparamagnetic iron oxide nanoparticles (SPIONs) Microscopy SQUID EELS Drug release Dorsal air pouch model Arthritis Intra-articular abstract Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into joints, but still suffer from the drawback of limited retention duration in the articular cavity. In this study, our aim was to prepare and characterize magnetic biodegradable microparticles containing dexamethasone acetate (DXM) for intra-articular administration. The superparamagnetic properties, which result from the encapsulation of superpara- magnetic iron oxide nanoparticles (SPIONs), allow for microparticle retention with an external magnetic field, thus possibly reducing their clearance from the joint. Two molecular weights of poly(lactic-co-gly- colic acid) (PLGA) were used, 12 and 19 kDa. The prepared batches were similar in size (around 10 lm), inner morphology, surface morphology, charge (neutral) and superparamagnetic behaviour. The SPION distribution in the microparticles assessed by TEM indicates a homogeneous distribution and the absence of aggregation, an important factor for preserving superparamagnetic properties. DXM release profiles were shown to be quite similar in vitro (ca. 6 days) and in vivo, using a mouse dorsal air pouch model (ca. 5 days). Ó 2009 Elsevier B.V. All rights reserved. 1. Introduction The use of carriers such as liposomes, nanoparticles or micro- particles for intra-articular administration of drugs has gained wide acceptance over drug suspensions or solutions. The advanta- ges of carriers lie in the fact that these delivery systems are, depending on their characteristics, cleared less rapidly from the joint, allowing for the active substance to be gradually released, and avoiding side effects such as crystal-induced arthritis [1]. The field of intra-articular-controlled drug delivery was pioneered by Ratcliffe et al. [2], who prepared albumin microspheres that could delay the clearance of a model drug from the joint, thus forming the rationale for intra-articular injections of microspheres. Moreover, the study also demonstrated that the clearance of this type of microparticle from the joint, known to be driven by syno- vial capillary and lymphatic transports, takes place within a few days after injection. This study, with others [3,4], spurred the search for methods offering more controlled and prolonged deliv- ery to the joint, focusing on ways to avoid rapid clearance. Our approach can also be included among the studies in this field. Specifically, the aim of our work was to prepare and charac- terize dexamethasone acetate-containing magnetic poly(lactic-co- glycolic acid) (PLGA) microparticles suitable for intra-articular injection for the treatment of arthritis or osteoarthritis. The ratio- nale for formulating magnetic microparticles by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) into the polymer matrix is to enhance the retention of the microparticles in the joint with an external magnetic field. Compared to other pa- pers reporting on the iron oxide encapsulation into polymer micro- particles [5–8], rather restricted in number, our article describes the technology of co-encapsulation of iron oxide and a drug, pro- cess only very rarely seen in other works. Furthermore, in contrast to the encapsulation of iron oxide as oleic acid-coated SPIONs described in other reports, which, despite a high encapsulation content, could generate problems of toxicity, we encapsulate the SPIONs as an aqueous suspension, by a double emulsion–solvent evaporation method. The dose of dexamethasone that needs to 0939-6411/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2009.03.003 * Corresponding author. School of Pharmaceutical Sciences, University of Geneva, 30 Quai Ernest Ansermet, Sciences II, 1211 Geneva 4, Switzerland. Tel.: +41 223796562; fax: +41 223796567. E-mail address: Nicoleta.Butoescu@unige.ch (N. Butoescu). European Journal of Pharmaceutics and Biopharmaceutics 72 (2009) 529–538 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb