Recent advances in hydrogel-based delivery systems for the treatment of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year survival rate below 10 %, largely due to late diagnosis, aggressive progression, and intrinsic resistance to conventional therapies. The dense desmoplastic stroma, hypoxic and acidic tumor microenvironment (TME), and profound immunosuppression severely limit drug penetration and efficacy. Hydrogels, as three-dimensional cross-linked polymer networks with high water content, biocompatibility, and tunable physicochemical properties, have emerged as versatile platforms for localized and sustained drug delivery in PDAC. Tailored designs enable hydrogels to respond to TME stimuli, achieving on-demand release and minimizing systemic toxicity. Recent advances demonstrate their utility in delivering chemotherapeutics, immunomodulators, photosensitizers, and gene cargos, as well as serving as scaffolds for tissue engineering and cell therapy. These multifunctional systems enhance intertumoral drug accumulation, remodel the TME, and synergize multimodal therapies to improve antitumor efficacy. Preclinical studies highlight significant tumor suppression and reduced recurrence with favorable safety profiles. However, challenges remain in long-term biosafety, scalable manufacturing, and precise <i>in vivo</i> delivery. This review summarizes current strategies, key advances, and translational challenges of hydrogel-based delivery systems for PDAC, offering insights into their potential to overcome therapeutic bottlenecks and advance toward clinical application.