Nonlinear dependence of hydraulic conductivity on tissue deformation during intratumoral infusion.
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.
McGuire
Sarah
S
Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27708, USA.
Zaharoff
David
D
Yuan
Fan
F
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001692:Biological Transport; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D004548:Elasticity; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007263:Infusions, Parenteral / Q000379:methods; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy*
D000970:Antineoplastic Agents; D003094:Collagen