title: Sulforaphane-PLGA microspheres for the intra-articular treatment of osteoarthritis.
abstract: Sulforaphane (SFN) is a member of the isothiocyanate family that has anti-inflammatory action as well as anti-carcinogenic properties. The authors have devised an intra-articular injectable SFN-PLGA microsphere system that can be used for treating osteoarthritis (OA). The purpose of this study was to evaluate the in vitro and in vivo efficacy of the SFN-PLGA microsphere system. Articular chondrocytes were obtained from knee OA patients and were cultured in monolayers. The optimal concentration of SFN was obtained and the dose of SFN-PLGA microspheres was determined based on the concentration. The in vitro anti-inflammatory effect on markers such as cyclooxygenase (COX)-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, and matrix metalloproteinase (MMP)-2 was assessed by real-time PCR and Western blotting. The in vivo therapeutic effect of SFN-PLGA microspheres was investigated using surgically-induced rat OA model. Treatment with SFN-PLGA microspheres inhibited the mRNA and protein expression of COX-2, ADAMTS-5 and MMP-2 induced by LPS in articular chondrocytes. Intraarticular SFN-PLGA microspheres delayed the progression of surgically-induced osteoarthritis in rats. In conclusion, SFN-PLGA microspheres can be a useful injectable delivery system for treating osteoarthritis.
authors.affiliation: Department of Orthopaedics, Dongguk University Ilsan Hospital, Goyang, Republic of Korea.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Ko
authors.forename: You-Jeong
authors.initials: YJ
authors.lastname: Choi
authors.forename: Geun-Jae
authors.initials: GJ
authors.lastname: Jeong
authors.forename: Gun-Il
authors.initials: GI
authors.lastname: Im
mesh_terms: D000368:Aged; D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology
chemical_list: D017879:Isothiocyanates; D013454:Sulfoxides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C016766:sulforaphane