title: A computational model of drug delivery through microcirculation to compare different tumor treatments.
abstract: Starting from the fundamental laws of filtration and transport in biological tissues, we develop a computational model to capture the interplay between blood perfusion, fluid exchange with the interstitial volume, mass transport in the capillary bed, through the capillary walls and into the surrounding tissue. These phenomena are accounted at the microscale level, where capillaries and interstitial volume are viewed as two separate regions. The capillaries are described as a network of vessels carrying blood flow. We apply the model to study drug delivery to tumors. The model can be adapted to compare various treatment options. In particular, we consider delivery using drug bolus injection and nanoparticle injection into the blood stream. The computational approach is suitable for a systematic quantification of the treatment performance, enabling the analysis of interstitial drug concentration levels, metabolization rates and cell surviving fractions. Our study suggests that for the treatment based on bolus injection, the drug dose is not optimally delivered to the tumor interstitial volume. Using nanoparticles as intermediate drug carriers overrides the shortcomings of the previous delivery approach. This work shows that the proposed theoretical and computational framework represents a promising tool to compare the efficacy of different cancer treatments.
authors.affiliation: MOX, Department of Mathematics "Francesco Brioschi", Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cattaneo
authors.forename: P
authors.initials: P
authors.lastname: Zunino
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002196:Capillaries / Q000502:physiology; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008833:Microcirculation; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D033081:Shear Strength; D000077704:Tirapazamine; D014227:Triazines / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D014227:Triazines; D000077704:Tirapazamine; D010100:Oxygen
keywords: blood perfusion; drug delivery; mass transport; microvascular environment