title: Characterization and evaluation of triamcinolone, raloxifene, and their dual-loaded microspheres as prospective local treatment system in rheumatic rat joints.
abstract: In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubility of the drug and hydrophobic nature of PCL. However, when coloaded with TA, both drugs were released at higher amounts compared with their single forms. Smallest particle sizes were obtained in dual drug-loaded microspheres. In vitro cytotoxicity tests showed biocompatibility of microspheres. In vivo bioefficacy of these microspheres was also examined in adjuvant-induced arthritis model in rats. In vivo histological studies of control groups showed development of RA with high median lesion score (5.0). Compared with control and intra-articular free drug injections, microsphere treatment groups showed lower lesion scores and better healing outcomes in histological evaluations. Results suggest that a controlled delivery system of TA and RAL by a single injection in inflamed joints holds promise for healing and suppressing inflammation.
authors.affiliation: Department of Biomedical Engineering, Middle East Technical University, Ankara, 06800, Turkey.
authors.forename: Yigit
authors.initials: Y
authors.lastname: Ocal
authors.forename: Baris
authors.initials: B
authors.lastname: Kurum
authors.forename: Siyami
authors.initials: S
authors.lastname: Karahan
authors.forename: Aysen
authors.initials: A
authors.lastname: Tezcaner
authors.forename: Seza
authors.initials: S
authors.lastname: Ozen
authors.forename: Dilek
authors.initials: D
authors.lastname: Keskin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008863:Microspheres; D011091:Polyesters / Q000737:chemistry; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D014221:Triamcinolone / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D003692:Delayed-Action Preparations; D011091:Polyesters; D014221:Triamcinolone; C016240:polycaprolactone; D020849:Raloxifene Hydrochloride
keywords: controlled release; drug delivery; intra-articular applications; microspheres; polycaprolactone; polymeric biomaterials; raloxifene; site specific delivery; triamcinolone