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For \u223c80% of borderline, non\u2010resectable, or metastatic cases, chemotherapy is predominantly palliative, underscoring the need for improved drug delivery approaches. This study presents the development, characterization and in vivo evaluation of a novel polymeric implant loaded with 5\u2010fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Scanning electron microscopy of FIRINOX implants showed internal microstructure was preserved upon drug loading, while micro\u2010CT and X\u2010ray imaging revealed valuable insights into the morphology and degradation of implants retrieved from in vivo experiments. In murine PDAC models, dose\u2010escalation identified 4 \u00d7 FIRINOX implants as the maximum tolerated dose, while 2 \u00d7 implants achieved significant therapeutic efficacy at lower doses than IV administration, without compromising animal safety. In healthy pigs, 20 \u00d7 FIRINOX implants were well\u2010tolerated, as confirmed by histopathology and blood analysis. Finally, laser ablation\u2010inductively coupled plasma\u2010mass spectrometry imaging and microbiome analysis confirmed localized drug perfusion within tissues, and minimal off\u2010target effects, including preservation of gut microbiota diversity. These findings support the potential of this implantable platform to improve outcomes in borderline or non\u2010resectable PDAC and enhance tolerability of cytotoxic chemotherapy through localized, controlled delivery, addressing a key gap where current treatment options are limited.<\/jats:p>","DOI":"10.1002\/adma.202522617","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:53:56Z","timestamp":1773640436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety Assessment of 5\u2010Fluorouracil, Irinotecan and Oxaliplatin\u2010Loaded Implants in Mouse and Pig Models for Pancreatic Cancer Therapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Samantha J.","family":"Wade","sequence":"first","affiliation":[{"name":"School of Science, Molecular Horizons University of Wollongong  Wollongong NSW 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