Nonlinear dependence of hydraulic conductivity on tissue deformation during intratumoral infusion

Sarah McGuire, David Zaharoff, Fan Yuan

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Efficiency of intratumoral infusion for drug and gene delivery depends on intrinsic tissue structures as well as infusion-induced changes in these structures. To this end, we investigated effects of infusion pressure (P inf) and infusion-induced tissue deformation on infusion rate (Q) in three mouse tumor models (B16.F10, 4T1, and U87) and developed a poroelastic model for interpreting data and understanding mechanisms of fluid transport in tumors. The collagen concentrations in these tumors were 2.9±1.2, 12.2±0.9, and 18.1±3.5 μg/mg wet wt. of tissues, respectively. During the infusion, there existed a threshold infusion pressure (P t), below which fluid flow could not be initiated. The values of P t for these tumors were 7.36, 36.8, and 29.4 mmHg, respectively. Q was a bell-shaped function of P inf in 4T1 tumors but increased monotonically with increasing P inf in other tumors. These observations were consistent with results from numerical simulations based on the poroelastic model, suggesting that both the existence of P t and the nonlinear relationships between Q and P inf could be explained by infusion-induced tissue deformation that anisotropically affected the hydraulic conductivity of tissues. These results may be useful for further investigations of intratumoral infusion of drugs and genes.

Original languageEnglish (US)
Pages (from-to)1173-1181
Number of pages9
JournalAnnals of Biomedical Engineering
Volume34
Issue number7
DOIs
StatePublished - Jul 1 2006

Keywords

  • Collagen concentration
  • Drug and gene delivery
  • Hydraulic conductivity
  • Intratumoral infusion

ASJC Scopus subject areas

  • Biomedical Engineering

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