Effect of extracellular matrix elements on the transport of paclitaxel through an arterial wall tissue mimic

Biomacromolecules. 2008 Oct;9(10):2792-8. doi: 10.1021/bm800571s. Epub 2008 Sep 12.

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.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Aorta / metabolism
  • Arteries / drug effects*
  • Arteries / pathology
  • Diffusion
  • Dose-Response Relationship, Drug
  • Elastin / chemistry
  • Endothelium, Vascular / pathology
  • Exons
  • Extracellular Matrix / metabolism
  • Glass
  • Humans
  • Microscopy, Fluorescence
  • Models, Statistical
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics*
  • Reproducibility of Results

Substances

  • Antineoplastic Agents, Phytogenic
  • Elastin
  • Paclitaxel