Celecoxib-loaded PEA microspheres as an auto regulatory drug-delivery system after intra-articular injection.
In this study, we investigated the potential of celecoxib-loaded polyester amide (PEA) microspheres as an auto-regulating drug delivery system for the treatment of pain associated with knee osteoarthritis (OA). Celecoxib release from PEA microspheres and inflammation responsive release of a small molecule from PEA was investigated in vitro. Inflammation responsive release of a small molecule from PEA was observed when PEA was exposed to cell lysates obtained from a neutrophil-like Hl-60 cell line. Following a short initial burst release of ~15% of the total drug load in the first days, celecoxib was slowly released throughout a period of >80days. To investigate biocompatibility and degradation behavior in vivo, celecoxib-loaded PEA microspheres were injected in OA-induced (ACLT+pMMx) or contralateral healthy knee joints of male Lewis rats. Bioactivity of celecoxib from loaded PEA microspheres was confirmed by PGE2measurements in total rat knee homogenates. Intra-articular biocompatibility was demonstrated histologically, where no cartilage damage or synovial thickening and necrosis were observed after intra-articular injections with PEA microspheres. Degradation of PEA microspheres was significantly higher in OA induced knees compared to contralateral healthy knee joints, while loading the PEA microspheres with celecoxib significantly inhibited degradation, indicating a drug delivery system with auto regulatory behavior. In conclusion, this study suggests the potential of celecoxib-loaded PEA microspheres to be used as a safe drug delivery system with auto regulatory behavior for treatment of pain associated with OA of the knee.
Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands.
Maarten
M
Janssen
Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands. Electronic address: u.timur@maastrichtuniversity.nl.
Ufuk Tan
UT
Timur
DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
Nina
N
Woike
Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands.
Tim J M
TJ
Welting
DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
Guy
G
Draaisma
Department of Pathology, Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, The Netherlands; Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands.
Marion
M
Gijbels
Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands.
Lodewijk W
LW
van Rhijn
DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
George
G
Mihov
DSM Biomedical, Koestraat 1, 6167 RA Geleen, The Netherlands.
Jens
J
Thies
Department of Orthopaedic Surgery, Research School CAPHRI, Maastricht University Medical Centre, P. Debyelaan, 25, 6229 HX Maastricht, The Netherlands.
Pieter J
PJ
Emans
D000818:Animals; D000068579:Celecoxib / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation; D002470:Cell Survival; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D018922:HL-60 Cells; D006706:Homeostasis; D006801:Humans; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D009757:Nylons / Q000737:chemistry*; D010003:Osteoarthritis / Q000188:drug therapy*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011917:Rats, Inbred Lew; D013499:Surface Properties
D052246:Cyclooxygenase 2 Inhibitors; D009757:Nylons; D011091:Polyesters; D000068579:Celecoxib
Autoregulation; Drug-delivery; Microspheres; Osteoarthritis; Polyester amide; Slow release