Fluid flow and transport of biotherapeutics through a 3D hybrid discrete-continuum vessel network in the skin tissue*

Subcutaneous administration is a common approach for the delivery of biotherapeutics, which is achieved mainly through the absorption across lymphatic vessels. The drug transport and lymphatic uptake through a three-dimensional hybrid discrete-continuum vessel network in the skin tissue are investigated through high-fidelity numerical simulations. We find that the local lymphatic uptake through the explicit vessels significantly affects the macroscopic drug absorption. The diffusion of drug solute through the explicit vessel network affects the lymphatic uptake after the injection. This effect, however, cannot be captured using previously developed continuum models. Furthermore, the effects of injection volume and depth on the lymphatic uptake are investigated in a multi-layered domain. We find that the injection volume significantly affects the rate of the lymphatic uptake through the heterogeneous vessel network, while the injection depth has little influence. At last, the binding and metabolism of drug molecules are studied to bridge the simulation to the experimentally measured drug clearance. We provide a new approach to study the diffusion and convection of drug molecules into the lymphatic system through the hybrid vessel network.