Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma

Neal Bhutiani, Steven Agle, Yan Li, Suping Li, Robert C G Martin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Introduction: Irreversible electroporation (IRE) utilizes short, high-voltage pulses to irreversibly permeabilize the cell membrane, resulting in apoptotic cell death. In addition to the irreversible zone, IRE creates a reversible zone that could be utilized for enhanced drug delivery. The hypothesis of this study is that a zone of reversible electroporation exists and allows for increased chemotherapy delivery. Methods: Ten immunocompromised mice with orthotopic human pancreatic adenocarcinoma tumors (Panc1) were treated with either IRE between two doses of gemcitabine (15 mg/kg) (ECT) (N = 5) or gemcitabine alone (N = 5). Gemcitabine levels in the serum, liver, and pancreas were analyzed with liquid chromatography/mass spectrometry (LC/MS). Results: Concentration of gemcitabine within reversibly electroporated pancreatic tissue was higher in mice receiving ECT compared to those receiving gemcitabine alone (13,567 ng/ml vs.4,126 ng/ml; P = 0.0009). Pancreatic gemcitabine levels were 5.52 and 5.96 times higher than liver and serum levels, respectively, in the ECT group compared to 2.85 and 2.53 times higher (P = 0.117, P = 0.058), respectively, in mice receiving gemcitabine alone. Conclusion: IRE can potentially reduce local recurrence by allowing increased drug delivery to the tissue in the reversible electroporation zone. This holds significant potential in augmenting efficacy of gemcitabine in treatment of locally advanced and borderline resectable pancreatic adenocarcinoma. J. Surg. Oncol. 2016;114:181–186.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalJournal of Surgical Oncology
Volume114
Issue number2
DOIs
StatePublished - Aug 1 2016

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gemcitabine
Electroporation
Adenocarcinoma
Liver
Serum
Liquid Chromatography
Pharmaceutical Preparations
Pancreas
Mass Spectrometry

Keywords

  • electrochemotherapy
  • electroporation
  • gemcitabine
  • irreversible electroporation
  • pancreatic cancer
  • reversible

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma. / Bhutiani, Neal; Agle, Steven; Li, Yan; Li, Suping; Martin, Robert C G.

In: Journal of Surgical Oncology, Vol. 114, No. 2, 01.08.2016, p. 181-186.

Research output: Contribution to journalArticle

Bhutiani, Neal ; Agle, Steven ; Li, Yan ; Li, Suping ; Martin, Robert C G. / Irreversible electroporation enhances delivery of gemcitabine to pancreatic adenocarcinoma. In: Journal of Surgical Oncology. 2016 ; Vol. 114, No. 2. pp. 181-186.
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