Mathematical modelling of hollow microneedle-mediated transdermal drug delivery.

Abstract

Hollow microneedles represent a promising approach for overcoming the protective barrier of the stratum corneum, facilitating direct drug infusion into viable skin tissue and thereby enhancing the efficacy of transdermal delivery. However, delivery outcomes across different skin layers and into the systemic circulation can vary substantially due to the diverse properties of drug delivery systems, clinical settings, and environmental factors. The optimal strategies for enhancing the efficiency of hollow microneedle-mediated transdermal drug delivery remain to be elucidated. This study employs mathematical modelling and a reconstructed skin model with realistic anatomical structures to investigate drug transport and accumulation across different skin layers and into the bloodstream under different delivery conditions. The modelling results reveal the crucial role of interstitial fluid flow in determining drug transport in this transdermal delivery. Delivery outcomes of each skin layer and blood exhibit distinct responses to changes in delivery conditions. Specifically, increasing the vascular permeability or nanocarrier diffusivity raises drug concentration in the blood or reticular dermis, respectively, while leading to reductions in other skin layers. The use of microneedles with narrower infusion channels can only enhance drug availability in the viable epidermis. Optimisation requires a tailored approach to several parameters depending on the target skin layer, including drug release rate, infusion rate, infusion duration, and microneedle length. Environmental factors that promote trans-epidermal water loss can increase drug concentration in the viable epidermis but have a limited impact on deeper skin tissues. The findings support the selection or customisation of hollow microneedles and nanocarriers to address specific therapeutic needs, such as targeting specific skin layers or systemic circulation, while minimising the risk of side effects from high drug concentrations in normal tissues. This study provides guidance for optimising transdermal drug delivery systems.