Transport and distribution of biotherapeutics in different tissue layers after subcutaneous injection

The subcutaneous injection is the main route of administration for monoclonal antibodies (mAbs) and several other biotherapeutics due to the patient comfort and cost-effectiveness. However, their transport and distribution after subcutaneous injection is poorly understood. Here, we exploit a three-dimensional poroelastic model to find the biomechanical response of the tissue, including interstitial pressure and tissue deformation during the injection. We quantify the drug concentration inside the tissue. We start with a single-layer model of the tissue. We show that during the injection, the difference between the permeability of the solvent and solute will result in a higher drug concentration proportional to the inverse permeability ratio. Then we study the role of tissue layered properties with primary layers, including epidermis, dermis, subcutaneous (SQ), and muscle layers, on tissue biomechanical response to injection and drug transport. We show that the drug will distribute mainly in the SQ layer due to its lower elastic moduli. Finally, we study the effect of secondary tissue elements like the deep fascia layer and the network of septa fibers inside the SQ tissue. We use the Voronoi tessellation algorithm to create random geometry of the septa network. We show how drugs accumulate around these tissue components as observed in the experimental SQ injection. Next, we study the effect of injection rate on drug concentration. We show how higher injection rates will slightly increase the drug concentration around septa fibers. Finally we demonstrate how the concentration dependent viscosity will increase the concentration of biotherapeutics in the direction of septa fibers.