title: Paclitaxel releasing films consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) and their potential as biodegradable stent coatings.
abstract: Although substantial progress in catheter and stent design has contributed to the success of percutaneous transluminal angioplasty (PTA) of atherosclerotic disease, the incidence of restenosis caused by in-stent neointimal hyperplasia remains a serious problem. Therefore, stents with a non-degradable polymer coating showing controlled release of active ingredients have become an attractive option for the site-specific delivery of anti-restenotic agents. Biodegradable coatings using polyesters, namely poly(lactic-co-glycolic acid) (PLGA) and different poly(vinyl alcohol)-graft-poly(lactic-co-glycolic acid) (PVA-g-PLGA) as paclitaxel-eluting stent coating materials were investigated here to evaluate their influence on the release kinetic. Whereas PLGA showed sigmoid release behavior, the paclitaxel release from PVA-g-PLGA films was continuous over 40 days without initial drug burst. Wide angle X-ray diffraction confirmed that paclitaxel is dissolved in the polymer matrix. Paclitaxel crystallization can be observed at a drug load of > or =10%. The effect of drug loading on polymer degradation was studied in films prepared from PVA300-g-PLGA30 with paclitaxel loadings of 5% and 15% over a time period of 6 weeks. The results suggest a surface-like erosion mechanism in films. A model stent (Jostent peripheral) coated with Parylene N, a poly(p-xylylene) (PPX) derivate, was covered with a second layer of PVA300-g-PLGA15, and PVA300-g-PLGA30 by using airbrush method. Morphology of coated stents, and film integrity after expansion from 3.12 to 5 mm was investigated by scanning electron microscopy (SEM). The devices resisted mechanical stress during stent expansion and merit further investigation under in vivo conditions.
authors.affiliation: Philipps University Marburg, Faculty of Pharmacy and Biopharmaceutics, Ketzerbach 63, 35032 Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Westedt
authors.forename: Matthias
authors.initials: M
authors.lastname: Wittmar
authors.forename: Michael
authors.initials: M
authors.lastname: Hellwig
authors.forename: Phillip
authors.initials: P
authors.lastname: Hanefeld
authors.forename: Andreas
authors.initials: A
authors.lastname: Greiner
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Schaper
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000737:chemistry; D001673:Biodegradation, Environmental; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D015607:Stents; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol; D017239:Paclitaxel