Effect of Extracellular Matrix Elements on the Transport of Paclitaxel through an Arterial Wall Tissue Mimic

详细信息    查看全文

• 作者：Rachael W. Sirianni ; John Kremer ; Ismail Guler ; Yen-Lane Chen ; Fred W. Keeley ; W. Mark Saltzman
• 刊名：Biomacromolecules
• 出版年：2008
• 出版时间：October 13, 2008
• 年：2008
• 卷：9
• 期：10
• 页码：2792-2798
• 全文大小：199K
• 年卷期：v.9,no.10(October 13, 2008)
• ISSN：1526-4602

文摘

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.