Development of a Physiologically-Based Mathematical Model for Quantifying Nanoparticle Distribution in Tumors.

Nanomedicine holds promise for the treatment of cancer, as it enables tumor-targeted drug delivery. However, reports on translation of most nanomedicine strategies to the clinic so far have been less than satisfactory, in part due to insufficient understanding of the effects of nanoparticle (NP) physiochemical properties and physiological variables on their pharmacological behavior. In this paper, we present a multiscale mathematical model to examine the efficacy of NP delivery to solid tumors; as a case example, we apply the model to a clinically detectable primary pancreatic ductal adenocarcinoma (PDAC) to assess tissue-scale spatiotemporal distribution profiles of NPs. We integrate NP systemic disposition kinetics with NP-cell interactions in PDAC abstractly described as a two-dimensional structure, which is then parameterized with human physiological data obtained from published literature. Through model analysis of delivery efficiency, we verify the multiscale approach by showing that NP concentration kinetics of interest in various compartments predicted by the whole-body scale model were in agreement with those obtained from the tissue-scale model. We also found that more NPs were trapped in the outer well-perfused tumor region than the inner semi-necrotic domain. Further development of the model may provide a useful tool for optimal NP design and physiological interventions.