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.