Gefitinib/gefitinib microspheres loaded polyurethane constructs as drug-eluting stent coating.
One of the complications of bronchotracheal cancer is obstruction of the upper airways. Local tumor resection in combination with an airway stent can suppress intraluminal tumor (re)growth. We have investigated a novel drug-eluting stent coating for local release of the anticancer drug gefitinib. A polyurethane (PU) sandwich construct was prepared by a spray coating method in which gefitinib was embedded between a PU support layer of 200μm and a PU top layer of 50-200μm. Gefitinib was either embedded in the construct as small crystals or as gefitinib-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSP). The drug was incorporated in the PU constructs with high recovery (83-93%), and the spray coating procedure did not affect the morphologies of the embedded microspheres as demonstrated by scanning electron microscopy (SEM), confocal laser scanning microscopy and fluorescence microscopy analysis. PU constructs loaded with gefitinib crystals released the drug for 7-21days and showed diffusion based release kinetics. Importantly, directional release of the drug towards the top layer, which is supposed to face the tumor mass, was controlled by the thicknesses of the PU top layer. PU constructs loaded with gefitinib microspheres released the drug in a sustained manner for >6months indicating that drug release from the microspheres became the rate limiting step. In conclusion, the sandwich structure of drug-loaded PLGA microspheres in PU coating is a promising coating for airway stents that release anticancer drugs locally for a prolonged time.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Weiluan
W
Chen
Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Pauwelsstraße 20, 52074, Germany.
Johanna
J
Clauser
Department of Biohybrid & Medical Textiles (BioTex), AME-Helmholtz Institute for Biomedical Engineering, ITA-Institut für Textiltechnik, RWTH Aachen University, Aachen, Germany.
Anja Lena
AL
Thiebes
Biomechanics Research Centre, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, University Road, Galway, Ireland.
Donnacha J
DJ
McGrath
Biomechanics Research Centre, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, University Road, Galway, Ireland.
Nicola
N
Kelly
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Mies J
MJ
van Steenbergen
Department of Biohybrid & Medical Textiles (BioTex), AME-Helmholtz Institute for Biomedical Engineering, ITA-Institut für Textiltechnik, RWTH Aachen University, Aachen, Germany.
Stefan
S
Jockenhoevel
Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Pauwelsstraße 20, 52074, Germany.
Ulrich
U
Steinseifer
Biomechanics Research Centre, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, University Road, Galway, Ireland.
Peter E
PE
McHugh
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Wim E
WE
Hennink
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. Electronic address: r.j.kok@uu.nl.
Robbert J
RJ
Kok
D003692:Delayed-Action Preparations; D065546:Drug Liberation; D054855:Drug-Eluting Stents; D005079:Excipients / Q000737:chemistry; D000077156:Gefitinib; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011140:Polyurethanes / Q000737:chemistry*; D011799:Quinazolines / Q000737:chemistry*
D003692:Delayed-Action Preparations; D005079:Excipients; D011140:Polyurethanes; D011799:Quinazolines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077156:Gefitinib
Bronchotracheal stent; Controlled release; Drug-eluting stents; Polymeric microspheres; Polyurethane