Subcutaneous Drug Delivery: A Review of the State-of-the-Art Modeling and Experimental Techniques

Abstract

Delivery of drug formulations through the subcutaneous route is a widely used modality for the treatment of several diseases, such as diabetes and autoimmune conditions. Subcutaneous injections are typically used to inject low-viscosity drugs in small doses. However, for new biologics, there is a need to deliver drugs of higher viscosity in large volumes. The response of subcutaneous tissue to such high-volume doses and higher viscosity injections is not well understood. Animal models have several drawbacks such as relevance to humans, lack of predictive power beyond the immediate population studied, cost, and ethical considerations. Therefore, a computational framework that can predict the tissue response to subcutaneous injections would be a valuable tool in the development of new devices. To model subcutaneous drug delivery, one needs to consider: a) the deformation and damage mechanics of skin layers due to needle penetration and b) the coupled fluid flow and deformation of the hypodermis tissue due to drug delivery The deformation of the skin is described by the anisotropic, hyper-elastic, and viscoelastic constitutive laws. The damage mechanics is modelled using appropriate damage criteria and damage evolution laws in the modelling framework. The deformation of the subcutaneous space due to fluid flow is described by the poro-hyperelastic theory. The objective of this review is to provide a comprehensive overview of the methodologies used to model each of the above-mentioned aspects of subcutaneous drug delivery. We also present an overview of the experimental techniques used to obtain various model parameters.

Modelling the Mechanical Behavior of Collagenous Materials by Considering Multiscale Effects

“…This also facilitates implementation of the multi-FEM model in commercial solvers like Abaqus [34]. In the absence of a closed-form of the strain energy density function, one needs to solve the multiscale mechanics equations (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) for each element in the mesh. This will increase the computational complexity of the problem significantly.…”

Advancements in Sustained‐Release Drug Delivery Systems

“…Nasal, ophthalmic, rectal, and vaginal drug delivery approaches have also seen notable advancements, expanding the possibilities for tailored therapeutic strategies [15][16][17][18] Transdermal and Subcutaneous Drug Delivery Transdermal drug delivery systems have gained prominence due to their non-invasive nature and sustained release capabilities [19]. Subcutaneous drug delivery, on the other hand, offers innovative solutions for various medical conditions [20]. Understanding the modelling and experimental techniques related to these routes is crucial for their successful implementation [20].…”

“…Subcutaneous drug delivery, on the other hand, offers innovative solutions for various medical conditions [20]. Understanding the modelling and experimental techniques related to these routes is crucial for their successful implementation [20].…”

Modelling the Mechanical Behavior of Collagenous Materials by Considering Multiscale Effects

“…Though continuum mechanics models ignore the microstructure of the tissue, they have been extremely successful in predicting the macroscopic response. Some examples include, modelling the anisotropic mechanical response of skin (Ní Annaidh, et al 2012), anisotropic response of arteries (Gasser, Ogden and Holzapfel 2006), modelling subcutaneous drug delivery (Leng, de Lucio and Gomez 2021) (Sharma, et al 2023), damage mechanics due to steerable needles (Terzano, et al 2020) etc.…”