Multi-field modeling and computational optimization of a subcutaneous insulin injection port

The present study proposes an advanced multi-field modeling approach to optimize in silico subcutaneous insulin release. We introduce a generalized fluid-pharmacokinetics framework, integrating syringe injection and subcutaneous permeability, thus advancing a first-of-its-kind computational model of insulin delivery port. The proposed theoretical framework comprises three main elements: (1) a realistic geometry model of a commercial port device and the surrounding subcutaneous tissues; (2) a staggered fluid dynamics model of syringe injection coupled with a multi-compartmental model of insulin absorption within a porous medium; (3) a computational-based device optimization to minimize the onset of lipodystrophies due to multiple injection procedures. A novel tissue lesion model is advanced, linking local subcutaneous pressure levels to altered permeability that comprise accumulation effects due to repeated injections. The computational framework was fine-tuned according to state-of-the-art experimental evidence, and extensive numerical analyses predicted unexplored insulin port devices behaviors thus allowing comparison of computed haematic insulin profiles with those obtained clinically. Accordingly, a vast parametric analysis was performed to identify the optimal conditions that minimize tissue lesions and support prolonged device usage.