Engineering and preclinical development of hydrogels for dermatologic drug delivery.

Hydrogels are increasingly used in drug delivery to the skin to control where and when therapeutics act. For clinical translation, a set of consistent experimental practices are important to ensure relevance to humans. This article provides an engineering-driven framework for designing and assessing hydrogel-based delivery systems in the skin, spanning topical films, injectable depots, hydrogel-forming microneedles, and hybrid architectures. Rational design of a hydrogel starts with defining the target skin compartment and the intended exposure endpoint and then establishes quantitative exposure assays and boundary conditions before formulation optimization. Payloads such as small molecules, proteins, and nucleic acids each have unique considerations that impact development. We outline criteria for polymer selection and crosslinking chemistries, followed by quality control experimental assays in engineering. A comprehensive series of preclinical experiments will individually assess layer-resolved exposure, spatial distribution, site-of-action kinetics, and pharmacodynamic response, with attention to translational requirements, including sterility, stability, storage, and reporting standards. This article equips skin researchers to generate comparable, reliable data and to advance hydrogel technologies toward clinical translation.