title: Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform.
abstract: Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA loaded microspheres were shown to release TAA for over 60days in PBS. Furthermore, the bioactivity lasted at least 28days, demonstrated by a 80-95% inhibition of PGE2production using TNFα-stimulated chondrocyte culture, indicating inhibition of inflammation. Microspheres loaded with the near infrared marker NIR780-iodide injected in healthy rat joints or joints with mild collagenase-induced OA showed retention of the microspheres up till 70days after injection. After intra-articular injection of TAA-loaded microspheres, TAA was detectable in the serum until day seven. Synovial inflammation was significantly lower in OA joints injected with TAA-loaded microspheres based on histological Krenn scores. Injection of TAA-loaded nor empty microspheres had no effect on cartilage integrity as determined by Mankin scoring. In conclusion, the PEA platform shows safety and efficacy upon intra-articular injection, and its extended degradation and release profiles compared to the currently used PLGA platforms may render it a good alternative. Even though further in vivo studies may need to address dosing and readout parameters such as pain, no effect on cartilage pathology was found and inflammation was effectively lowered in OA joints.
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Imke
authors.initials: I
authors.lastname: Rudnik-Jansen
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Sascha
authors.initials: S
authors.lastname: Colen
authors.affiliation: DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
authors.forename: Julien
authors.initials: J
authors.lastname: Berard
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80163, 3508 TD Utrecht, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Plomp
authors.affiliation: Department of Radiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Mattie
authors.initials: M
authors.lastname: van Rijen
authors.affiliation: DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
authors.forename: Nina
authors.initials: N
authors.lastname: Woike
authors.affiliation: Division Laboratory and Pharmacy, Clinical Pharmacy, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Egas
authors.affiliation: Department of Orthopaedics & Otorhinolaryngology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Gerjo
authors.initials: G
authors.lastname: van Osch
authors.affiliation: Division Laboratory and Pharmacy, Clinical Pharmacy, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Maarseveen
authors.affiliation: DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
authors.forename: Ken
authors.initials: K
authors.lastname: Messier
authors.affiliation: Department of Radiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Alan
authors.initials: A
authors.lastname: Chan
authors.affiliation: DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
authors.forename: Jens
authors.initials: J
authors.lastname: Thies
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: l.b.creemers@umcutrecht.nl.
authors.forename: Laura
authors.initials: L
authors.lastname: Creemers
mesh_terms: D000577:Amides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D008863:Microspheres; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D011091:Polyesters; D014222:Triamcinolone Acetonide; D015232:Dinoprostone
keywords: Corticosteroids; Inflammation; Intra-articular; Microspheres; Osteoarthritis