title: The role of the microvascular network structure on diffusion and consumption of anticancer drugs.
abstract: We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy-double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells. The coefficients are then injected into the macroscale equations, and these are solved for an isolated, vascularized spherical tumor. We consider the effect of vascular tortuosity on the transport of anticancer molecules, focusing on Vinblastine and Doxorubicin dynamics, which are considered as a tracer and as a highly interacting molecule, respectively. The computational model is able to quantify the treatment performance through the analysis of the interstitial drug concentration and the quantity of drug metabolized in the tumor. Our results show that both drug advection and diffusion are dramatically impaired by increasing geometrical complexity of the microvasculature, leading to nonoptimal absorption and delivery of therapeutic agents. However, this effect apparently has a minor role whenever the dynamics are mostly driven by metabolic reactions in the tumor interstitium, eg, for highly interacting molecules. In the latter case, anticancer therapies that aim at regularizing the microvasculature might not play a major role, and different strategies are to be developed.
authors.affiliation: Dipartimento di Ingegneria Civile, Edile ed Ambientale, Università di Padova, Via Marzolo 9, 35131, Padua, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Mascheroni
authors.affiliation: Departamento de Mecanica de los Medios Continuos y T. Estructuras, E.T.S. de caminos, canales y puertos, Universidad Politecnica de Madrid, Calle Profesor Aranguren S/N, 28040, Madrid, Spain.
authors.forename: Raimondo
authors.initials: R
authors.lastname: Penta
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D004058:Diffusion; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D055806:Microvessels / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin
keywords: advection-diffusion-reaction; asymptotic homogenization; computational modeling; drug delivery; tumor microvasculature