Efficient human breast cancer xenograft regression after a single treatment with a novel liposomal formulation of epirubicin prepared using the EDTA ion gradient method

Jerzy Gubernator; Dominik Lipka; Mariola Korycińska; Katarzyna Kempińska; Magdalena Milczarek; Joanna Wietrzyk; Rafał Hrynyk; Sabine Barnert; Regine Süss; Arkadiusz Kozubek

doi:10.1371/journal.pone.0091487

Efficient human breast cancer xenograft regression after a single treatment with a novel liposomal formulation of epirubicin prepared using the EDTA ion gradient method

PLoS One. 2014 Mar 12;9(3):e91487. doi: 10.1371/journal.pone.0091487. eCollection 2014.

Affiliations

¹ Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
² Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Wrocław, Poland.
³ Department of Personal Protective Equipment. Central Institute for Labour Protection - National Research Institute, Warsaw, Poland.
⁴ Department of Pharmaceutical Technology, Albert-Ludwigs University, Freiburg, Germany.

Abstract

Liposomes act as efficient drug carriers. Recently, epirubicin (EPI) formulation was developed using a novel EDTA ion gradient method for drug encapsulation. This formulation displayed very good stability and drug retention in vitro in a two-year long-term stability experiment. The cryo-TEM images show drug precipitate structures different than ones formed with ammonium sulfate method, which is usually used to encapsulate anthracyclines. Its pharmacokinetic properties and its efficacy in the human breast MDA-MB-231 cancer xenograft model were also determined. The liposomal EPI formulation is eliminated slowly with an AUC of 7.6487, while the free drug has an AUC of only 0.0097. The formulation also had a much higher overall antitumor efficacy than the free drug.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / blood
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Breast Neoplasms / pathology*
Cell Line, Tumor
Cell Proliferation / drug effects
Chemistry, Pharmaceutical / methods*
Cholesterol / chemistry
Edetic Acid / chemistry*
Epirubicin / administration & dosage
Epirubicin / blood
Epirubicin / chemistry*
Epirubicin / pharmacology*
Humans
Kinetics
Liposomes
Male
Mice
Phosphatidylcholines / chemistry
Phosphatidylethanolamines / chemistry
Polyethylene Glycols / chemistry
Xenograft Model Antitumor Assays*

Substances

Antineoplastic Agents
Liposomes
Phosphatidylcholines
Phosphatidylethanolamines
1,2-distearoylphosphatidylethanolamine
Polyethylene Glycols
Epirubicin
Cholesterol
Edetic Acid

Grants and funding

This study was supported by the Pharmaceutical Research Institute, Warsaw, Poland. The funders had only role in drug and cancer type selection, but not on data collection and analysis, decision to publish, or preparation of the manuscript.