Model-based analysis of nanocarrier-mediated transdermal drug delivery with coated microneedles

Coated microneedles represent a promising strategy to overcome the barrier of the stratum corneum in transdermal delivery, enabling direct administration of drugs into viable skin tissues and systemic circulation. However, the delivery performance to different skin layers and the blood circulation depend strongly on the characteristics of the drug delivery system, which can vary considerably. In this study, a mathematical model incorporating a reconstructed skin structure with realistic anatomical features is developed to investigate how key, practically controllable parameters influence dynamic drug transport and accumulation within each homogeneous, isotropic skin layer and systemic blood. In particular, distributed models based on a set of convection-diffusion-reaction equations are employed to describe drug transport between the microneedle and multiple skin layers, whereas the coupled kinetic models are used to simulate drug transport within the blood compartments. The skin model consists of the stratum corneum (15 μm), viable epidermis (100 μm), papillary dermis (350 μm), and reticular dermis (800 μm). This study specifically examines drug transport through the transepidermal pathway, with appendageal transport neglected. The results confirm the capability of coated microneedles to effectively deliver nanocarrier-encapsulated drugs to both local tissues and systemic circulation. Drug concentrations generally decrease with increasing tissue depth, and delivery outcomes differ markedly among tissue compartments. Importantly, each skin layer responds differently to variations in nanocarrier and coating properties. Parameters such as nanocarrier diffusivity in the coating layer and skin tissues, interfacial transfer rate, transvascular permeability, coating thickness, and drug release kinetics significantly affect drug distribution. Some factors enhance systemic exposure at the expense of skin retention, whereas others favour local accumulation while limiting systemic transport. These findings highlight the importance of parameter optimisation according to the intended therapeutic objective, whether targeting specific skin layers or systemic circulation. Overall, this study provides mechanistic insights that support the rational design and advancement of coated microneedle-based drug delivery systems for enhanced efficacy in transdermal therapy.