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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 microg/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.

The intratumoral field, which determines the efficiency of electric field-mediated drug and gene delivery, can differ significantly from the applied field. Therefore, we investigated the distribution of the electric field in mouse tumors and tissue phantoms exposed to a large range of electric stimuli, and quantified the resistances of tumor, skin, and electrode-tissue interface. The samples used in the study included 4T1 and B16.F10 tumors, mouse skin, and tissue phantoms constructed with 1% agarose gel with or without 4T1 cells. When pulsed electric fields were applied to samples using a pair of parallel-plate electrodes, we determined the electric field and resistances in each sample as well as the resistance at the electrode-tissue interface. The electric fields in the center region of tissue phantoms and tumor slices ex vivo were macroscopically uniform and unidirectional between two parallel-plate electrodes. The field strengths in tumor tissues were significantly lower than the applied field under both ex vivo and in vivo conditions. During in vivo stimulation, the ratio of intratumoral versus applied fields was approximately either 20% or 55%, depending on the applied field. Meanwhile, the total resistance of skin and electrode-tissue interface was decreased by approximately 70% and the electric resistance at the center of both tumor models was minimally changed when the applied field was increased from 50 to 400 V/cm. These results may be useful for improving electric field-mediated drug and gene delivery in solid tumors.