Multiphysics modelling of the impact of skin deformation and strain on microneedle-based transdermal therapeutic...

Microneedle patches (MNs) hold enormous potential to facilitate the minimally-invasive delivery of drugs and vaccines transdermally. However, the micro-mechanics of skin deformation significantly influence the permeation of therapeutics through the skin. Previous studies often fail to appreciate the complexities in microneedle-skin mechanical interactions. This may impede the accuracy of MNs pre-clinical assessments. Here, we develop a multiphysics finite element model which simulates the biomechanics of microneedle skin penetration and the subsequent permeation of therapeutics. Employing the aqueous pore path hypothesis, we consider how strain (induced through the insertion of a MN), affects pore geometry in the skin and therefore the diffusion of therapeutics. Our models show that considering the insertion-induced skin deformation alone reduces the transdermal permeation of insulin by 25 %, while considering the effect of strain can reduce the overall permeation by a further 45 % over 24 h. Our model also indicates that once the mechanical strain is removed i.e. through removal or dissolution of the array, the permeation through the skin will recover. Furthermore, our results indicate that the delivery of high molecular weight compounds may be most susceptible to strain-induced changes in drug permeation. These findings could have significant implications for the preferred type of microneedle administration when targeting, for example, intradermal or transdermal delivery. STATEMENT OF SIGNIFICANCE: This manuscript presents an advanced computational model of microneedle insertion into human skin. Here, we adopt a multiphysics modelling strategy, where we predict the influence of microneedle insertion on skin deformation and strain and how that influences subsequent therapeutic permeation through the skin. Our model predicts that whether or not the microneedle remains in situ, the resultant change in tissue deformation and strain has a major impact on how quickly the therapeutic diffuses through the skin. This has important implications for transdermal device design, administration strategies and protocols and associated clinical studies, where either intradermal or transdermal therapeutic delivery is being targetted.