Efficacy and Safety Assessment of 5-Fluorouracil, Irinotecan and Oxaliplatin-Loaded Implants in Mouse and Pig Models for Pancreatic Cancer Therapy

  • Adv Mater. 2026 May;38(26):e22617. doi: 10.1002/adma.202522617.
Samantha J Wade  1 ,  Ashna A Kumar  1 ,  Samuel O Nitschke  2 ,  Paul Joyce  2 ,  Elahe Minaei  1 ,  Stephanie E Reuter  2 ,  Chelsea Penney  1 ,  Holly Warren  1 ,  Ruby Shepherd  1 ,  Jeremy N Dinoro  3 ,  Gordon G Wallace  3 ,  Anthony Dosseto  4 ,  Sameera Ansar  5 ,  Naila Islam  5 ,  Alistair Lochhead  5 ,  George Sharbeen  6 ,  Phoebe A Phillips  6 ,  Morteza Aghmesheh  7  8 ,  Wayne J Hawthorne  9  10  11 ,  Kara L Vine-Perrow  1
Affiliations
  • 1. School of Science, Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia.
  • 2. School of Pharmacy and Biomedical Science, Adelaide University, Adelaide, SA, Australia.
  • 3. Intelligent Polymer Research Institute and Australian National Fabrication Facility - Materials Node, Innovation Campus, University of Wollongong, Wollongong, NSW, Australia.
  • 4. Wollongong Isotope Geochronology Laboratory, Environmental Futures, University of Wollongong, Wollongong, NSW, Australia.
  • 5. Southern IML Pathology, Sonic Healthcare, Coniston, NSW, Australia.
  • 6. School of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.
  • 7. Nelune Comprehensive Cancer Centre, Bright Building, Prince of Wales Hospital, Sydney, NSW, Australia.
  • 8. Faculty of Medicine and Health, UNSW, Sydney, NSW, Australia.
  • 9. Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.
  • 10. Westmead Institute of Medical Research, Westmead, NSW, Australia.
  • 11. Department of Surgery, Westmead Hospital, Westmead, NSW, Australia.
PMID: 41834342 DOI: 10.1002/adma.202522617
Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) remains highly resistant to treatment, with mortality rates largely unchanged despite advances in Cancer therapies. For ∼80% of borderline, non-resectable, 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-fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Scanning electron microscopy of FIRINOX implants showed internal microstructure was preserved upon drug loading, while micro-CT and X-ray imaging revealed valuable insights into the morphology and degradation of implants retrieved from in vivo experiments. In murine PDAC models, dose-escalation identified 4 × FIRINOX implants as the maximum tolerated dose, while 2 × implants achieved significant therapeutic efficacy at lower doses than IV administration, without compromising animal safety. In healthy pigs, 20 × FIRINOX implants were well-tolerated, as confirmed by histopathology and blood analysis. Finally, laser ablation-inductively coupled plasma-mass spectrometry imaging and microbiome analysis confirmed localized drug perfusion within tissues, and minimal off-target effects, including preservation of gut microbiota diversity. These findings support the potential of this implantable platform to improve outcomes in borderline or non-resectable PDAC and enhance tolerability of cytotoxic chemotherapy through localized, controlled delivery, addressing a key gap where current treatment options are limited.

Keywords
FOLFIRINOX; implant; localized drug delivery; pancreatic cancer.
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