Three-dimensional simulation of IgG delivery to tumors

Abstract

A simulation method is developed to study the extravascular and transvascular transport of interstitial fluids and MAbs in primitive neuroectodermal tumors (PNET). Two cases of drug delivery are investigated: systemic administration and polymer-based controlled release. The effects of necrotic core, lymphatic vessels and binding kinetics on the drug distribution are examined. A few indices (mean concentration, ISN and SR) are used to characterize the distribution of MAbs. It is found that the controlled drug release from polymer is basically a localized release in which drug concentration in the vicinity of polymer is high. Compared with systemic administration, polymeric controlled release gives higher drug concentration with reduced systemic toxicity. Penetration depth of the drug is more dependent on the transvascular permeability than the diffusivity. In searching for the optimal location of the polymer, the implantation in the viable zone of tumor seems to be a better choice since it can give higher drug concentrations in both the viable zone and the necrotic core. Functional lymphatic vessels drastically reduce the interstitial pressure and the MAb concentration. The binding of drug with tissues reduces the free drug concentrations in the viable zone and normal tissues.