title: In vitro evaluation of paclitaxel coatings for delivery via drug-coated balloons.
abstract: Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to treat occluded blood vessel. They were developed for the rapid transfer of antiproliferative drugs during the angioplasty procedure in stenosed vessels with the intent to reduce the risk of restenosis. In this study five different paclitaxel (PTX) balloon coatings were tested in vitro in order to examine how solvents and additives influence coating stability and drug transfer rates. PTX-coated balloons were advanced through a guiding catheter and a simulated coronary artery pathway under perfusion and were then inflated in a hydrogel acceptor compartment. The fractions transferred to the gel, remaining on the balloon and the PTX lost in the simulated coronary pathway were then analysed. The results obtained suggest that the solvent used for the coating process strongly influences the surface structure and the stability of the coating. Ethanol/water and acetone based PTX coatings showed the lowest drug transfer rates to the simulated vessel wall (both <1%) due to their high drug losses during the prior passage through the coronary artery model (more than 95%). Balloons coated with PTX from ethyl acetate-solutions showed smaller drug loss (83%±9%), but most of the remaining PTX was not transferred (mean balloon residue approximately 15%). Beside the solvent, the use of additives seemed to have a great impact on transfer properties. The balloon pre-treatment with a crosslinked polyvinylpyrrolidone (PVP) film was able to increase the PTX transfer rate from less than 1% (without PVP) to approximately 6%. The best results in this study were obtained for balloon coatings with commercially available SeQuent© Please balloons containing the contrast agent iopromide. For this formulation drug transfer rates of approximately 17% were determined. Fluorescence microscopic imaging could visualize the particulate transfer of labelled PTX from the balloon surface during dilatation. The findings of this study underline the importance of drug adhesion and coating stability for the efficiency of PTX transfer.
authors: Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany.
authors: Wiebke
authors: W
authors: Kempin
authors: Institute for Biomedical Engineering, University of Rostock, 18119 Rostock, Germany.
authors: Sebastian
authors: S
authors: Kaule
authors: Institute for Biomedical Engineering, University of Rostock, 18119 Rostock, Germany.
authors: Thomas
authors: T
authors: Reske
authors: Institute for Biomedical Engineering, University of Rostock, 18119 Rostock, Germany.
authors: Niels
authors: N
authors: Grabow
authors: Institute for Biomedical Engineering, University of Rostock, 18119 Rostock, Germany.
authors: Svea
authors: S
authors: Petersen
authors: Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany.
authors: Stefan
authors: S
authors: Nagel
authors: Institute for Biomedical Engineering, University of Rostock, 18119 Rostock, Germany.
authors: Klaus-Peter
authors: KP
authors: Schmitz
authors: Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany.
authors: Werner
authors: W
authors: Weitschies
authors: Institute of Pharmacy, Center of Drug Absorption and Transport, University of Greifswald, 17487 Greifswald, Germany. Electronic address: anne.seidlitz@uni-greifswald.de.
authors: Anne
authors: A
authors: Seidlitz
mesh_terms: D000003:Abattoirs; D065567:Absorption, Physiological; D000268:Adhesiveness; D000327:Adsorption; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D002339:Carotid Arteries / Q000737:chemistry / Q000378:metabolism*; D003287:Contrast Media / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D066298:In Vitro Techniques; D007472:Iohexol / Q000031:analogs & derivatives / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D011205:Povidone / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D034421:Sus scrofa
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D005079:Excipients; D012997:Solvents; D007472:Iohexol; C038192:iopromide; D011205:Povidone; D017239:Paclitaxel
keywords: Coronary artery model; Drug-coated balloon; In vitro drug transfer; Paclitaxel; Vessel simulation