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Consequently, the development of effective drug delivery strategies capable of overcoming stromal and resistance barriers remains an urgent clinical priority. Poly (lactic\u2010co\u2010glycolic acid) (PLGA) nanoparticles have emerged as a versatile biomaterials platform for improving therapeutic outcomes through enhanced drug solubility, sustained release, and favorable pharmacokinetics. This review critically examines recent advances in the rational design and functionalization of PLGA\u2010based nanocarriers for PDAC therapy, with particular emphasis on tumor\u2010targeted delivery, stromal modulation, and strategies to overcome multidrug resistance. Surface engineering approaches, including ligand conjugation and stimuli\u2010responsive systems, have shown considerable promise in enhancing intratumoral penetration and therapeutic efficacy. In addition, advanced nanoscale analytical and interfacial characterization techniques such as dynamic light scattering, electron microscopy, and zeta potential analysis provide important mechanistic insights into particle stability, cellular interactions, and drug\u2013polymer dynamics, thereby guiding formulation optimization. Collectively, current evidence highlights the strong translational potential of PLGA nanocarriers in precision oncology for PDAC. Continued integration of biomaterials engineering with disease\u2010specific targeting and rigorous physicochemical characterization will be essential to accelerate clinical development and improve patient outcomes.<\/jats:p>","DOI":"10.1002\/ddr.70307","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:40:38Z","timestamp":1778647238000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Programmable Poly\u2010Lactic\u2010Co\u2010Glycolic Acid Nanocarriers for Precision Therapy of Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","volume":"87","author":[{"given":"Shruti","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Bioscience and Biomedical Engineering Indian Institute of Technology Bhilai, Kutelabhata Durg Chhattisgarh 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