Drug penetration in solid tumors: influence of drug size and capillary architecture

INTRODUCTION: Macromolecular and nanoparticulate drug carriers are increasingly important in oncology due to improved targeting and reduced systemic toxicity; however, their delivery to solid tumors is often limited by size-dependent transport barriers. METHODS: We present a computational modeling framework that couples microvascular blood flow, transvascular exchange, interstitial fluid flow, and macromolecule transport to investigate the interplay between drug properties, particularly particle size, and tumor capillary structural characteristics. A stochastic capillary network generation algorithm was developed to produce realistic microvascular networks with heterogeneous vessel radius, branching patterns, and permeability properties. RESULTS: Simulations show an inverse relationship between particle size and penetration and quantify how pore radius and pore area fraction modulate extravasation and tissue dispersion. CONCLUSIONS: Overall, the framework may serve as a prototype in silico tool for drug formulation design, supporting the selection of molecular formats and sizes that distribute more efficiently within tumors under tumor-specific biophysical constraints.