title: Dexamethasone-containing PLGA superparamagnetic microparticles as carriers for the local treatment of arthritis.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) are attractive materials that have been widely used in medicine for diagnostic imaging and therapeutic applications. In our study, SPIONs and the corticosteroid dexamethasone acetate (DXM) are co-encapsulated into PLGA microparticles for the aim of locally treating inflammatory conditions such as arthritis. The magnetic properties conferred by the SPIONs could help to maintain the microparticles in the joint with an external magnet. The aim of this study was to investigate the interaction between magnetic microparticles and human synovial fibroblasts in terms of microparticle uptake (FACS, confocal and optical microscopy), internalization mechanism (Prussian Blue staining, TEM, immunofluorescence), cell toxicity (MTT) and tissue reaction after intra-articular injection (histology). The results show that the microparticles have an excellent biocompatibility with synoviocytes and that they are internalized through a phagocytic process, as demonstrated by fluorescence-activated cell sorting and morphological analyses of cells exposed to microparticles. Histological analysis showed that the prepared microparticles did not induce any inflammatory reaction in the joint. This type of carrier could represent a suitable magnetically retainable intra-articular drug delivery system for treating joint diseases such as arthritis or osteoarthritis.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, Switzerland. nicoleta.butoescu@unige.ch
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Butoescu
authors.forename: Christian A
authors.initials: CA
authors.lastname: Seemayer
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Foti
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
authors.forename: Eric
authors.initials: E
authors.lastname: Doelker
mesh_terms: D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D005295:Ferrocyanides; D006801:Humans; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D008280:Magnetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D005295:Ferrocyanides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015638:Cytochalasin D; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; C000170:ferric ferrocyanide