1. Effect of Extracellular Matrix Elements on the Transport of Paclitaxel through an Arterial Wall Tissue Mimic.
- Author
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Rachael W. Sirianni, John Kremer, Ismail Guler, Yen-Lane Chen, Fred W. Keeley, and W. Mark Saltzman
- Subjects
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EXTRACELLULAR matrix proteins , *PACLITAXEL , *CONNECTIVE tissues , *DRUG side effects - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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