title: Gemcitabine-releasing polymeric films for covered self-expandable metallic stent in treatment of gastrointestinal cancer.
abstract: Non-vascular drug-eluting stents have been studied for the treatment of gastrointestinal cancer and cancer-related stenosis. In this study, we designed and evaluated a gemcitabine (GEM)-eluting covered nonvascular stent. Polyurethane (PU)/polytetrafluoroethylene (PTFE) film was selected for the drug loading and eluting membrane. The membrane was fabricated by dip-coating on a Teflon bar (∅; 10mm), air-dried, peeled off and applied to a self-expanding Nitinol stent. Various amounts of poloxamer 407 (PL, Lutrol F127, BASF) (8%, 10%, or 12% of PU by weight) were added to control the release of GEM from membranes. The membrane containing 12% PL (GEM-PU-PL12%) showed the most favourable release properties; 70% of the loaded GEM released within 35 days, including the 35% released during the initial burst. The biological activities of GEM-PU-PL12% were evaluated using human cholangiocarcinoma cells (SK-ChA-1). GEM-PU-PL12% most efficiently inhibited the proliferation of cholangiocarcinoma cells and most highly induced pro-inflammatory cytokines (TNF-α, IL-1β and IL-12) and p38 MAPKs in the cells. Subtumoural insertion of the GEM-PU-PL12% membrane more efficiently inhibited the growth of CT-26 colon cancer than other membranes. In this study, the GEM-eluting metal stents covered with PU-PL12% showed considerable feasibility for the treatment of malignant gastrointestinal cancer as well as cancer-related stenosis.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43-1 Yokkok2-dong, Wonmi-gu, Bucheon 420-743, South Korea.
authors.forename: Jang Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000497:Alloys; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000209:etiology; D016207:Cytokines / Q000096:biosynthesis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D054855:Drug-Eluting Stents; D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008567:Membranes, Artificial; D051379:Mice; D020442:Poloxamer; D011108:Polymers; D011138:Polytetrafluoroethylene; D011140:Polyurethanes; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000497:Alloys; D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D008567:Membranes, Artificial; D011108:Polymers; D011140:Polyurethanes; D003841:Deoxycytidine; D020442:Poloxamer; C013616:nitinol; D011138:Polytetrafluoroethylene; D048051:p38 Mitogen-Activated Protein Kinases; D000093542:Gemcitabine