Combined Numerical and Experimental Investigation of Solid Microneedle-Skin Interaction and Penetration

Microneedle patches have long been proposed as an effective platform for wearable diagnostics and enhanced transdermal drug delivery. However, microneedle patches suffer from inconsistent skin penetration and subsequent unreliable retention and therapeutic delivery, a severe impediment to realising their widespread clinical potential. A key factor in assessing the performance of microneedle (MN) patch designs and formulations is their capacity to successfully penetrate into skin. To address this need, I developed a state-of-the-art skin tissue model that reflects in vivo mechanical conditions of the skin, along with a constitutive equation for strain-dependent drug diffusion in tissue. It was experimentally validated using bespoke static 3D-printed Franz diffusion cells (FDCs) to investigate the influence of time-dependent skin strain and deformation on microneedle-based therapeutic delivery. The optimised 3D hyperelastic, anisotropic pre-stressed multi-layered skin material model, developed as part of this thesis, more accurately reflects in vivo skin conditions. It was used to determine that the level of skin tension affects both the microneedle penetration force and insertion efficiency, and quantified how adjacent microneedles impact the overall performance of the microneedle patch. Following on from this model, a further strain dependent transdermal drug delivery model was developed. This was coupled with skin deformation and skin strain due to MN insertion and retention, creating a Multiphysics model. This model indicated that the presence of mechanical strain, due to e.g. compression related to MN insertion significantly alters the permeation through the skin. Furthermore, once the mechanical strain is removed (through removal or dissolution of the MN array), the permeation through the skin will recover. The delivery of high molecular weight compounds may be most susceptible to strain-induced changes in drug permeation. This highlights the importance of microneedle administration modes when targeting, for example, intradermal or transdermal delivery. Histological fluorescent imaging analysis confirmed that the MNPs physically succeed in delivering the compounds with large molecular weights (>500 Daltons) through the transdermal drug delivery system but that their permeation is negatively impacted by the presence of mechanical strain. This resistance to drug permeation can be mitigated through the removal of mechanical strain e.g. through MN retraction or dissolution. Finally, the in vitro skin absorption assays, conducted using bespoke FDCs, experimentally validated the results of the multiphysics modelling.