title: Effect of extracellular matrix elements on the transport of paclitaxel through an arterial wall tissue mimic.
abstract: Paclitaxel (PTx) is reported to have an nonuniform steady-state concentration profile in the arterial wall. We utilized epifluorescence microscopy to make precise measurements of fluorescently-labeled PTx (F-PTx) distribution through an in vitro tissue mimic which contained varying concentrations of fibrin, elastin, soybean oil, palmitic acid, and solid glass beads. As little as 0.5 mg/mL of elastin in agarose produced a 50% drop in the measured diffusion coefficient, while as much as 10 mg/mL of fibrin in agarose was required for the same reduction in rate of transport. Because no reduction in the measured diffusion coefficient was observed for solubilized, extracted elastin or unassembled elastin-like polypeptides, the effect was specific to elastic fibers that closely resembled the native elastin network. Collectively, this work identifies a potential source for the high degree of partitioning observed for PTx in native tissue and further develops an in vitro technique for exploring complex tissue-drug interactions.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Sirianni
authors.forename: John
authors.initials: J
authors.lastname: Kremer
authors.forename: Ismail
authors.initials: I
authors.lastname: Guler
authors.forename: Yen-Lane
authors.initials: YL
authors.lastname: Chen
authors.forename: Fred W
authors.initials: FW
authors.lastname: Keeley
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics*; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000187:drug effects* / Q000473:pathology; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000737:chemistry; D004730:Endothelium, Vascular / Q000473:pathology; D005091:Exons; D005109:Extracellular Matrix / Q000378:metabolism; D005898:Glass; D006801:Humans; D008856:Microscopy, Fluorescence; D015233:Models, Statistical; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004549:Elastin; D017239:Paclitaxel