Moisture-responsive smart hydrogel for adaptive regulation of timolol delivery kinetics under variable wound exudate conditions

Effective wound therapy requires systems that respond to dynamic moisture conditions while enabling controlled drug delivery. This work focuses on the application of a previously developed programmable, humidity responsive hydrogel for exudate management in combination with targeted delivery of timolol, a β-adrenergic antagonist with emerging therapeutic relevance in wound healing. The influence of predefined hydrogel hydration and exudate levels on drug release and skin permeation across wounded and non-wounded skin was evaluated. The hydrated state of the hydrogel exhibited rapid diffusion-controlled drug release, whereas the conditioned hydrogel showed a biphasic swelling-controlled release behavior with initial polymer relaxation followed by predominantly diffusional transport. Higher exudate levels accelerated swelling and shifted the inflection point up to 2.7-fold earlier. Wounded skin showed rapid permeation, while non wounded skin exhibited pronounced lag phases and up to 77-fold lower permeation. The steady-state flux across wounded skin from the conditioned hydrogel was 1.7-fold lower compared to the hydrated hydrogel. The hydrogel exhibits a fluid handling capacity comparable to superabsorbent dressings while maintaining high moisture vapor transmission. Combining timolol with this smart and self-adjusting material paves the way for a novel category of personalized wound therapy adaptable to a broad range of wound states.