A Computational Framework to Model Tissue Response During Subcutaneous Injections

Abstract

Abstract Subcutaneous injections are commonly used to deliver drugs such as insulin and hormones. However, drug absorption shows significant inter-patient variability and intra-patient variability (with injection-site). Animal models, which are used to characterize this variability, have limitations due to differences between the structural and mechanical properties of human and animal skin. A robust in-silico framework that can predict the response of human tissue to subcutaneous injections can overcome these limitations. We present a finite element (FE) modelling framework to model subcutaneous drug delivery, that consists of two parts a) damage mechanics of skin due to needle insertion and b) coupled fluid flow and deformation of the subcutaneous space during drug delivery. An anisotropic and viscoelastic constitutive model for subcutaneous tissue was implemented and model parameters were estimated from bench-top testing of cadaveric human skin. The framework considers anisotropy in the mechanical and poroelastic transport properties to mimic the properties of human skin. In addition, our model also considers mechanical damage due to fluid-pressure during drug delivery. Deformation and stress state from needle insertion model are imported as an initial conditions into the poroelastic model. This integration of an anisotropic-viscoelastic constitutive model, damage mechanics and pore fracture represent a novel approach to capture the complex physics of subcutaneous injection. This model was used to investigate the influence of various subcutaneous injection parameters (flowrate, viscosity etc) on the subcutaneous drug transport. This model can be used to inform the design of novel delivery systems such as large volume injectors.