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Nonlinear Dependence of Hydraulic Conductivity on Tissue Deformation During Intratumoral Infusion

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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.

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Abbreviations

EBA:

evans blue-labeled albumin

ECM:

extracellular matrix

GAG:

glycosaminoglycan

IFP:

interstitial fluid pressure

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ACKNOWLEDGMENTS

We thank Ava Krol for tumor preparations. The work is supported in part by a grant from the National Science Foundation (BES-9984062).

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  1. Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC, 27708, USA

    Sarah McGuire, David Zaharoff & Fan Yuan

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  1. Sarah McGuire
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  2. David Zaharoff
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Correspondence to Fan Yuan.

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McGuire, S., Zaharoff, D. & Yuan, F. Nonlinear Dependence of Hydraulic Conductivity on Tissue Deformation During Intratumoral Infusion. Ann Biomed Eng 34, 1173–1181 (2006). https://doi.org/10.1007/s10439-006-9136-2

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  • DOI: https://doi.org/10.1007/s10439-006-9136-2

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