Photo-Responsive In Situ Forming Hydrogels for Drug Delivery: A Critical Review of Polymer Matrices, Photoinitiators, and the Gap Towards Clinical Translation

Local drug delivery increasingly relies on injectable hydrogels that form directly at the x‘administration site, among which light-cured systems are of particular interest: irradiation converts a liquid precursor into a depot and can trigger drug release with high spatiotemporal resolution. The aim of this critical narrative review is to systematize the key design elements of such systems and to assess their path toward the clinic. We analyze the mechanisms of photoactivation, the role of wavelength, the natural, synthetic, and hybrid polymer matrices together with their tuning parameters, and the photoinitiators. The clinical and preclinical experience in dentistry, ophthalmology, regenerative medicine, and oncology is then considered separately. Finally, we address standardization through the Quality by Design concept. We show that, despite an extensive preclinical base, no photocrosslinkable injectable depot for drug delivery has yet been approved, whereas photopolymerization itself and the photoinitiators employed are already accepted in the clinic in adjacent fields. We conclude that clinical translation is defined by three tractable tasks: qualifying photoinitiators for the injectable route of administration, overcoming the limited depth of light activation, and standardizing characterization on the basis of Quality by Design.