Comprehensive Modeling of Heat and Diffusional Drug Transfer in Photothermal-Responsive Microneedles Applied to Skin

Abstract Photothermal-responsive microneedles (PRMNs) are promising tools for controlled, on-demand transdermal delivery of low-permeability drugs like Methotrexate. While effective, their underlying heat and drug transfer mechanisms, particularly the role of Soret effect-induced thermodiffusion, remain unclear. This study develops a theoretical framework that integrates heat transfer induced by light irradiation with molecular transport governed by both Fick’s diffusion and the Soret effect while accounting for skin heterogeneity and temperature-dependent diffusion. Using a geometric PRMN-skin model, we numerically investigated the temperature distribution, temporal drug concentration, and cumulative drug amount under various irradiation conditions. Fluorescence experiments with polyvinyl alcohol PRMNs in porcine skin were performed, and the temperature evolution and temporal drug release were analyzed. The Soret effect was found to act as an active thermodiffusion mechanism augmenting the intrinsically concentration-gradient-driven transport. The current framework lays a foundation for instrumentation of PRMNs and optical components as a whole and their implementation as wearable devices thereafter.