Pharmaceutical Research

, Volume 32, Issue 3, pp 852–862 | Cite as

Pharmacokinetics, Antitumor and Cardioprotective Effects of Liposome-Encapsulated Phenylaminoethyl Selenide in Human Prostate Cancer Rodent Models

  • Jeong Yeon Kang
  • Mathew Eggert
  • Shravanthi Mouli
  • Ibrahim Aljuffali
  • Xiaoyu Fu
  • Ben Nie
  • Amy Sheil
  • Kendall Waddey
  • Charlie D. Oldham
  • Sheldon W. May
  • Rajesh Amin
  • Robert D. Arnold
Research Paper



Cardiotoxicity associated with the use of doxorubicin (DOX), and other chemotherapeutics, limits their clinical potential. This study determined the pharmacokinetics and antitumor and cardioprotective activity of free and liposome encapsulated phenyl-2-aminoethyl-selenide (PAESe).


The pharmacokinetics of free PAESe and PAESe encapsulated in liposomes (SSL-PAESe) were determined in rats using liquid chromatography tandem mass-spectrometry. The antitumor and cardioprotective effects were determined in a mouse xenograft model of human prostate (PC-3) cancer and cardiomyocytes (H9C2).


The encapsulation of PAESe in liposomes increased the circulation half-life and area under the drug concentration time profile, and decreased total systemic clearance significantly compared to free PAESe. Free- and SSL-PAESe improved survival, decreased weight-loss and prevented cardiac hypertrophy significantly in tumor bearing and healthy mice following treatment with DOX at 5 and 12.5 mg/kg. In vitro studies revealed PAESe treatment altered formation of reactive oxygen species (ROS), cardiac hypertrophy and gene expression, i.e., atrial natriuretic peptide and myosin heavy chain complex beta, in H9C2 cells.


Treatment with free and SSL-PAESe exhibited antitumor activity in a prostate xenograft model and mitigated DOX-mediated cardiotoxicity.


cardiotoxicity doxorubicin liposomes phenylaminoethyl selenide prostate cancer 





Atrial natriuretic peptide


Area under the plasma drug concentration-time curve




Total systemic clearance


Maximum plasma concentration


Coefficient of variation






1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]


Electrospray ionization


4-fluoro-phenyl-2-aminoethyl selenide


2′-7′- dichlorodihydrofluorescein diacetate


Internal standard


Terminal elimination rate


High performance liquid chromatography




Lower limit of quantification


Mass to charge




Myosin heavy chain complex beta


Multiple reaction monitoring


Mass spectrometry


Tandem mass spectrometry


Phenyl-2-aminoethyl selenide




Quality control


Quantitative polymerase chain reaction


Reactive oxygen species




Sterically-stabilized liposomes


Sterically stabilized PAESe liposomes




Apparent volume of distribution


Alpha distribution half-life


Beta elimination half-life


Acknowledgments and Disclosures

This research was funded in part by NIH 1R01 1EB016100-01 and 1R21 EB008153 (RDA), Auburn University Internal Grants Program, Georgia Cancer Coalition Distinguished Scholar Grant (RDA) and University of Georgia-Georgia Tech Seed Grant (SWM/RDA).

Supplementary material

11095_2014_1501_MOESM1_ESM.docx (116 kb)
Supplemental data (DOCX 115 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jeong Yeon Kang
    • 1
  • Mathew Eggert
    • 2
  • Shravanthi Mouli
    • 2
  • Ibrahim Aljuffali
    • 1
    • 4
  • Xiaoyu Fu
    • 2
  • Ben Nie
    • 2
  • Amy Sheil
    • 2
  • Kendall Waddey
    • 2
  • Charlie D. Oldham
    • 3
  • Sheldon W. May
    • 3
  • Rajesh Amin
    • 2
  • Robert D. Arnold
    • 2
  1. 1.Department of Pharmaceutical and Biomedical SciencesCollege of Pharmacy, University of GeorgiaAthensUSA
  2. 2.Department of Drug Discovery & DevelopmentHarrison School of Pharmacy, Auburn UniversityAuburnUSA
  3. 3.School of Chemistry & BiochemistryGeorgia Institute of TechnologyAtlantaUSA
  4. 4.Nanomedicine Research Unit, Department of PharmaceuticsCollege of Pharmacy, King Saud UniversityRiyadhSaudi Arabia

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