An acetylated polysaccharide-PTFE membrane-covered stent for the delivery of gemcitabine for treatment of gastrointestinal cancer and related stenosis

Abstract Gemcitabine (Gem) eluting metal stents were prepared for potential application as drug delivery systems for localized treatment of malignant tumors. Pullulan, a natural polysaccharide, was chemically acetylated (pullulan acetate; PA) by different degrees (1.18, 1.71, and 2.10 acetyl groups...

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Bibliographic Details
Published in:Biomaterials 2011-05, Vol.32 (14), p.3603-3610
Main Authors: Moon, Sumi, Yang, Su-Geun, Na, Kun
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Antimetabolites, Antineoplastic - administration & dosage
Antimetabolites, Antineoplastic - therapeutic use
Apoptosis - drug effects
Cell Line, Tumor
Colonic Neoplasms - drug therapy
Constriction, Pathologic - drug therapy
Covered stents
Dentistry
Deoxycytidine - administration & dosage
Deoxycytidine - analogs & derivatives
Deoxycytidine - therapeutic use
Drug-Eluting Stents
Gastrointestinal cancer
Gastrointestinal Neoplasms - drug therapy
Gemcitabine
Male
Mice
Mice, Inbred BALB C
Nonvascular drug-eluting stents (DES)
Polysaccharides - chemistry
Polytetrafluoroethylene - chemistry
Pullulan
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Summary:Abstract Gemcitabine (Gem) eluting metal stents were prepared for potential application as drug delivery systems for localized treatment of malignant tumors. Pullulan, a natural polysaccharide, was chemically acetylated (pullulan acetate; PA) by different degrees (1.18, 1.71, and 2.10 acetyl groups per glucose unit of pullulan), layered on polytetrafluoroethylene (PTFE), and applied as part of a Gem-loaded controlled-release membrane for drug-eluting non-vascular stents. PA with a higher degree of acetylation had greater drug-loading capacity with more extended release of Gem over 30 days. The released Gem accumulated in CT-26 colon cancer without systemic exposure inducing total regression of tumors. The long-term biological activity of the released Gem and apoptosis of tumor tissues following localized delivery were confirmed by annexin V binding assays and histology. The controlled release of Gem from PA-PTFE covered drug-eluting stents (DES) may increase the patency of these stents for the treatment of malignant gastrointestinal cancer as well as cancer-related stenosis.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2011.01.070