Programmable multi-stimuli photonic hydrogels for intelligent and adaptive transdermal drug delivery

Transdermal drug delivery (TDD) bypasses first-pass metabolism and improves patient compliance. However, conventional hydrogels are static and cannot adapt to dynamic physiological conditions. Stimuli-responsive photonic hydrogels overcome these limitations by integrating photonic triggers (e.g., photoisomerization, photothermal conversion) with biochemical sensors (e.g., glucose, reactive oxygen species (ROS), enzymes). These systems employ Boolean logic operations to achieve conditional, multi-input gated release. Proof-of-concept studies demonstrate a three-to-five-fold increase in skin penetration, > 70% tumor volume reduction with lower drug doses, and accelerated wound closure compared to passive hydrogels. Embedding these platforms into microneedles and wearable electronics enables real-time, feedback-controlled dosing, while artificial intelligence (AI) offers predictive, closed-loop optimization. Despite their promise, clinical translation requires overcoming challenges in biocompatibility, manufacturing scalability, and regulatory classification. A roadmap emphasizing standardized safety testing, modular fabrication, and AI-guided prototyping is essential. Photonic hydrogels thus mark a paradigm shift, advancing transdermal systems from static depots to adaptive, autonomous therapeutics for personalized medicine.