Journal article
Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer
Cancer chemotherapy and pharmacology, Vol.81(6), pp.991-998
06/01/2018
DOI: 10.1007/s00280-018-3570-3
PMCID: PMC6753584
PMID: 29603014
Abstract
Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor vascularization that is characteristic of pancreatic cancer. The local iontophoretic delivery of chemotherapies provides a novel way of improving treatment. With the growing practice of highly toxic combination therapies in the treatment of pancreatic cancer, the use of iontophoresis for local delivery can potentiate the anti-cancer effects of these therapies while sparing unwanted toxicity. The objective of this study was to investigate the impact of formulation on the electro-transport of the FOLFIRINOX regimen for the development of a new treatment for pancreatic cancer.
Three formulations of the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) were generated at a fixed pH of 6.0 and were referred to as formulation A (single drug solution with all four drugs combined), formulation B (two drug solutions with two drugs per solution), and formulation C (four individual drug solutions). Anodic iontophoresis of the three different formulations was evaluated in orthotopic patient-derived xenografts of pancreatic cancer.
Iontophoretic transport of the FOLFIRINOX drugs was characterized according to organ exposure after a single device treatment in vivo. We report that the co-iontophoresis of two drug solutions, leucovorin + oxaliplatin and 5-fluorouracil + irinotecan, resulted in the highest levels of cytotoxic drugs in the tumor compared to drugs delivered individually or combined into one solution. There was no significant difference in plasma, pancreas, kidney, and liver exposure to the cytotoxic drugs delivered by the three different formulations. In addition, we found that reducing the duration of iontophoretic treatment from 10 to 5 min per solution resulted in a significant decrease in drug concentrations.
Underlying the difference in drug transport of the formulations was electrolyte concentrations, which includes both active and inactive components. Electrolyte concentrations can hinder or improve drug electro-transport. Overall, balancing electrolyte concentration is needed for optimal electro-transport.
Details
- Title: Subtitle
- Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer
- Creators
- James D. Byrne - University of North Carolina at Chapel HillMohammad R. N. Jajja - University of North Carolina at Chapel HillAdrian T. O'Neill - University of North Carolina at Chapel HillAllison N. Schorzman - University of North Carolina at Chapel HillAmanda W. Keeler - University of North Carolina at Chapel HillJ. Christopher Luft - University of North Carolina at Chapel HillWilliam C. Zamboni - University of North Carolina at Chapel HillJoseph M. DeSimone - University of North Carolina at Chapel HillJen Jen Yeh - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.81(6), pp.991-998
- DOI
- 10.1007/s00280-018-3570-3
- PMID
- 29603014
- PMCID
- PMC6753584
- NLM abbreviation
- Cancer Chemother Pharmacol
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- National Defense Science and Engineering Graduate Fellowship University Cancer Research Fund at the University of North Carolina P30CA016086 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIGMS-2-T32-GM008719 / UNC Medical Scientists Training Program T32GM008719 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) PhRMA Foundation Fellowship
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiation Oncology
- Record Identifier
- 9984274858002771
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