Figure 6.

Representations of tumour compartments in nanomaterial PBPK models. A. Complex representation of a multi-compartmental tumour structure subdivided into vascular, interstitial, and cellular sub-compartments and using the membrane limited organ model. The solid lines represent the transport of the nanomaterial and the dashed lines the transport of the payload. Graphic adapted from ¹²¹. B. Generic representation of tumour using the two-pore compartment formalism. The large pores (1.5 μm here) model transport of nanomaterials through intercellular openings due to convection (i.e., EPR effect) and the small pores (0.6 μm here) passive diffusion into and out of the tumour via transcellular pores ¹¹⁵. Note that the mathematical description of transport kinetics (as opposed to physical pore size) are what matters for model design work. These models generally yield superior simulations compared to standard membrane limited (or one-pore) models for antibodies ¹¹⁹. Graphic adapted from ¹¹⁸.