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

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

  • Adv Mater. 2026 Mar 15: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

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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