Advances and Hurdles of PLGA-Based Therapy for Pancreatic Cancer.

Pancreatic cancer (PC) is one of the most aggressive malignancies, with a very low 5-year survival rate due to late diagnosis, rapid metastasis, and resistance to conventional therapies. The pancreas's deep anatomical location complicates early detection, and most patients present with advanced or metastatic disease, limiting surgical options. Current chemotherapy regimens often face challenges such as systemic toxicity, poor tumor penetration, and acquired chemoresistance. To overcome these limitations, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) have emerged as a promising strategy for targeted drug delivery in PC treatment. PLGA NPs offer controlled drug release, enhanced bioavailability, and reduced off-target effects. Their surface can be functionalized with ligands to actively target PC cells, improving therapeutic efficacy while minimizing damage to healthy tissues. Additionally, PLGA NPs can encapsulate chemotherapeutics, siRNA, or immunomodulators, enabling combination therapy to combat drug resistance and tumor microenvironment barriers. Recent advances in nanomedicine highlight the potential of PLGA-based systems to enhance tumor accumulation, overcome stromal resistance, and improve therapy outcomes. This review discusses the current challenges in PC treatment, the role of PLGA NPs in targeted drug delivery, and future perspectives for clinical translation. Integrating PLGA NPs could revolutionize PC therapy, offering hope for improved survival and quality of life.