Abstract
PURPOSE AND OBJECTIVE: Microneedles have emerged as a promising platform for transdermal drug delivery, offering high patient compliance, ease of use, and minimal invasiveness. Despite extensive research on microneedle design and fabrication, the influence of intrinsic drug properties on delivery performance remains insufficiently understood. This study is aimed to determine the individual effects of key transport properties of the loaded drug on delivery outcomes across different skin layers and the systemic circulation. METHODS: A multiphysics model is employed to characterise transdermal drug delivery via microneedles, based on a multilayer skin model that incorporates realistic anatomical structures and dimensions. Nine key drug-related parameters are investigated, including drug diffusivity in the microneedle and skin tissues, partition coefficients between the tissue and microneedle, between the cell membrane and interstitial space, and between the cell interior and interstitial space, as well as the protein binding coefficient, transvascular permeability, elimination rate in the skin tissue, and plasma clearance. RESULTS: The simulations reveal distinct responses of drug delivery performance in each skin layer and in the blood circulation to variations in each property, with optimal values existing depending on the location of the therapeutic target within the skin. CONCLUSIONS: The findings provide mechanistic insights into the interplay between drug physicochemical characteristics and transdermal transport dynamics, offering valuable guidance for rational drug selection, formulation design, and the development of microneedle-based therapeutics.