Local iontophoretic administration of cytotoxic therapies to solid tumors

James D. Byrne; Mohammad N. R. Jajja; Adrian T. O’Neill; Lissett R. Bickford; Amanda W. Keeler; Nabeel Hyder; Kyle Wagner; Allison Deal; Ryan E. Little; Richard A. Moffitt; Colleen Stack; Meredith Nelson; Christopher R. Brooks; William Lee; J. Chris Luft; Mary E. Napier; David Darr; Carey K. Anders; Richard Stack; Joel E. Tepper; Andrew Z. Wang; William C. Zamboni; Jen Jen Yeh; Joseph M. DeSimone

doi:10.1126/scitranslmed.3009951

Research ArticleDrug Delivery

Local iontophoretic administration of cytotoxic therapies to solid tumors

James D. Byrne¹,²,*,
Mohammad N. R. Jajja³,*,
Adrian T. O’Neill³,
Lissett R. Bickford³,
Amanda W. Keeler⁴,
Nabeel Hyder⁵,
Kyle Wagner⁵,
Allison Deal⁶,
Ryan E. Little²,
Richard A. Moffitt³,
Colleen Stack³,⁷,⁸,
Meredith Nelson³,
Christopher R. Brooks⁹,
William Lee¹⁰,
J. Chris Luft¹,³,
Mary E. Napier³,
David Darr³,
Carey K. Anders³,¹¹,
Richard Stack³,⁸,¹²,
Joel E. Tepper³,⁵,
Andrew Z. Wang³,⁵,
William C. Zamboni³,⁴,
Jen Jen Yeh³,¹³,¹⁴,† and
Joseph M. DeSimone¹,³,¹⁰,¹⁴,¹⁵,†

¹Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
²School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁶Lineberger Comprehensive Cancer Center Biostatistics and Clinical Data Management Core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷School of Medicine, Duke University, Durham, NC 27708, USA.
⁸Synecor LLC, Chapel Hill, NC 27517, USA.
⁹Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁰Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹¹Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹²Division of Cardiology, Department of Medicine, Duke University, Durham, NC 27708, USA.
¹³Division of Surgical Oncology, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁴Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
¹⁵Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA.

↵†Corresponding author. E-mail: jen_jen_yeh{at}med.unc.edu (J.J.Y); desimone{at}unc.edu (J.M.D.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 04 Feb 2015:
Vol. 7, Issue 273, pp. 273ra14
DOI: 10.1126/scitranslmed.3009951

James D. Byrne

1Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

2School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Mohammad N. R. Jajja

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Adrian T. O’Neill

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Lissett R. Bickford

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Amanda W. Keeler

4Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Nabeel Hyder

5Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Kyle Wagner

5Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Allison Deal

6Lineberger Comprehensive Cancer Center Biostatistics and Clinical Data Management Core, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Ryan E. Little

2School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Richard A. Moffitt

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Colleen Stack

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

7School of Medicine, Duke University, Durham, NC 27708, USA.

8Synecor LLC, Chapel Hill, NC 27517, USA.

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Meredith Nelson

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Christopher R. Brooks

9Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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William Lee

10Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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J. Chris Luft

1Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Mary E. Napier

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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David Darr

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Carey K. Anders

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

11Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Richard Stack

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

8Synecor LLC, Chapel Hill, NC 27517, USA.

12Division of Cardiology, Department of Medicine, Duke University, Durham, NC 27708, USA.

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Joel E. Tepper

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

5Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Andrew Z. Wang

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

5Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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William C. Zamboni

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

4Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Jen Jen Yeh

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

13Division of Surgical Oncology, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

14Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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For correspondence: jen_jen_yeh@med.unc.edu desimone@unc.edu

Joseph M. DeSimone

1Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

10Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

14Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

15Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA.

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For correspondence: jen_jen_yeh@med.unc.edu desimone@unc.edu

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Local administration of cytotoxic drugs using iontophoresis results in drug accumulation and therapeutic efficacy in mouse models of pancreatic and breast cancer and favorable PK in a large animal model.

Local iontophoretic administration of cytotoxic therapies to solid tumors

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