The role of initial lymphatics in the absorption of monoclonal antibodies after subcutaneous injection.

The subcutaneous injection is the most common method of administration of monoclonal antibodies (mAbs) due to the patient's comfort and cost-effectiveness. However, the available knowledge about the transport and absorption of this type of biotherapeutics after subcutaneous injection is limited. Here, a mathematical framework to study the subcutaneous drug delivery of mAbs from injection to lymphatic uptake is presented. A poro-hyperelastic model of the tissue is exploited to find the biomechanical response of the tissue together with a transport model based on an advection-diffusion equation in large-deformation poro-hyperelastic Media. The process of mAbs transport to the lymphatic system has two major parts. First is the initial phase, where mAbs are dispersed in the tissue due to momentum exerted by injection. This stage lasts for only a few minutes after the injection. Then there is the second stage, which can take tens of hours, and as a result, mAb molecules are transported from the subcutaneous layer towards initial lymphatics in the dermis to enter the lymphatic system. In this study, we investigate both stages. The process of plume formation, interstitial pressure, and velocity development is explored. Then, the effect of the injection delivery parameters, injection site, and sensitivity of long-term lymphatic uptake due to variability in permeability, diffusivity, viscosity, and binding of mAbs are investigated. Finally, we study two different injection scenarios with variable injection volume and drug concentration inside the syringe and evaluate them based on the rate of lymphatic uptake. We use our results to find an equivalent lymphatic uptake coefficient similar to the coefficient widely used in pharmacokinetic (PK) models to study the absorption of mAbs. Ultimately, we validate our computational model against available experiments in the literature.