Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of Biotherapeutics: Model Development.

Abstract

Many monoclonal antibodies (mAbs) are administered via subcutaneous (SC) injection. Local transport and absorption kinetics and mechanisms, however, remain poorly understood. A multiphysics computational model was developed to simulate the injection and absorption processes of a protein solution in the SC tissue. Quantitative relationships among tissue properties and transport behaviors of an injected solution were described by respective physical laws. SC tissue was treated as a 3-dimensional homogenous, poroelastic medium, in which vasculatures and lymphatic vessels were implicitly treated. Tissue deformation was considered, and interstitial fluid flow was modeled by Darcy's law. Transport of the drug mass was described based on diffusion and advection, which was integrated with tissue mechanics and interstitial fluid dynamics. Injection and absorption of albumin and IgG solutions were simulated. Upon injection, a sharp rise in tissue pressure, porosity, and fluid velocity could be observed at the injection tip. Largest tissue deformation appeared at the model surface. Transport of drug mass out of the injection zone was minimal. Absorption by local lymphatics was found to last several weeks. A bottom-up method was developed to simulate drug transport and absorption of protein solutions in skin tissue base on physical principles. The results appear to match experimental observations.