Beyond the skin barrier: from rational design to translational and market perspectives of hydrogel-forming microneedles.

The development of effective transdermal drug delivery systems remains a major challenge in modern pharmaceutics. Hydrogel-forming microneedles (HFMNs) have emerged as a promising platform, combining controlled drug release, biocompatibility, and minimally invasive administration. Their performance is strongly governed by the physicochemical and structural properties of the polymeric matrix, which regulate swelling behaviour, drug diffusion, and mechanical integrity. The selection of polymers, additives, and geometric parameters-such as needle height, base width, and array density-directly influences insertion efficiency, mechanical resistance, and drug release kinetics. This review critically analyses recent advances in the design and characterisation of HFMNs and proposes a rational framework linking matrix composition, structural architecture, and functional performance. By integrating insights from polymer chemistry, microneedle engineering, and drug delivery science, this work provides a structured perspective for tailoring HFMN systems to specific clinical needs, from rapid-onset delivery for acute pain to sustained administration for chronic conditions such as diabetes. Despite significant progress, challenges remain, including the lack of standardised protocols for mechanical testing and the underexplored potential of natural polymer diversity. Addressing these limitations will be crucial for accelerating the clinical translation of HFMN-based transdermal therapies.