Paclitaxel releasing films consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) and their potential as biodegradable stent coatings.
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.
Westedt
Ulrich
U
Philipps University Marburg, Faculty of Pharmacy and Biopharmaceutics, Ketzerbach 63, 35032 Marburg, Germany.
Wittmar
Matthias
M
Hellwig
Michael
M
Hanefeld
Phillip
P
Greiner
Andreas
A
Schaper
Andreas K
AK
Kissel
Thomas
T
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
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