Vitamin C-driven epirubicin loading into liposomes

Dominik Lipka,1 Jerzy Gubernator,1 Nina Filipczak,1 Sabine Barnert,2 Regine Süss,2 Mateusz Legut,1 Arkadiusz Kozubek1 1Department of Lipids and Liposomes, University of Wroclaw, Wroclaw, Poland; 2Department of Pharmaceutical Technology, Albert Ludwigs University, Freiburg, Germany Abstract:...

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Autores principales:	Lipka D, Gubernator J, Filipczak N, Barnert S, S&uuml;ss R, Legut M, Kozubek A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9042a6ac8c474f79930e3b36bc1c7b6e
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spelling	oai:doaj.org-article:9042a6ac8c474f79930e3b36bc1c7b6e2021-12-02T07:14:14ZVitamin C-driven epirubicin loading into liposomes1176-91141178-2013https://doaj.org/article/9042a6ac8c474f79930e3b36bc1c7b6e2013-09-01T00:00:00Zhttp://www.dovepress.com/vitamin-c-driven-epirubicin-loading-into-liposomes-a14447https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Dominik Lipka,1 Jerzy Gubernator,1 Nina Filipczak,1 Sabine Barnert,2 Regine Süss,2 Mateusz Legut,1 Arkadiusz Kozubek1 1Department of Lipids and Liposomes, University of Wroclaw, Wroclaw, Poland; 2Department of Pharmaceutical Technology, Albert Ludwigs University, Freiburg, Germany Abstract: The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI), its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment), and the free drug was shown to have no anticancer activity at the tested dose. Keywords: liposomes, epirubicin, vitamin C, antitumor activity, remote loading, ascorbic acidLipka DGubernator JFilipczak NBarnert SS&uuml;ss RLegut MKozubek ADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 3573-3585 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lipka D Gubernator J Filipczak N Barnert S S&uuml;ss R Legut M Kozubek A Vitamin C-driven epirubicin loading into liposomes
description	Dominik Lipka,1 Jerzy Gubernator,1 Nina Filipczak,1 Sabine Barnert,2 Regine Süss,2 Mateusz Legut,1 Arkadiusz Kozubek1 1Department of Lipids and Liposomes, University of Wroclaw, Wroclaw, Poland; 2Department of Pharmaceutical Technology, Albert Ludwigs University, Freiburg, Germany Abstract: The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI), its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment), and the free drug was shown to have no anticancer activity at the tested dose. Keywords: liposomes, epirubicin, vitamin C, antitumor activity, remote loading, ascorbic acid
format	article
author	Lipka D Gubernator J Filipczak N Barnert S S&uuml;ss R Legut M Kozubek A
author_facet	Lipka D Gubernator J Filipczak N Barnert S S&uuml;ss R Legut M Kozubek A
author_sort	Lipka D
title	Vitamin C-driven epirubicin loading into liposomes
title_short	Vitamin C-driven epirubicin loading into liposomes
title_full	Vitamin C-driven epirubicin loading into liposomes
title_fullStr	Vitamin C-driven epirubicin loading into liposomes
title_full_unstemmed	Vitamin C-driven epirubicin loading into liposomes
title_sort	vitamin c-driven epirubicin loading into liposomes
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/9042a6ac8c474f79930e3b36bc1c7b6e
work_keys_str_mv	AT lipkad vitamincdrivenepirubicinloadingintoliposomes AT gubernatorj vitamincdrivenepirubicinloadingintoliposomes AT filipczakn vitamincdrivenepirubicinloadingintoliposomes AT barnerts vitamincdrivenepirubicinloadingintoliposomes AT sampuumlssr vitamincdrivenepirubicinloadingintoliposomes AT legutm vitamincdrivenepirubicinloadingintoliposomes AT kozubeka vitamincdrivenepirubicinloadingintoliposomes
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Vitamin C-driven epirubicin loading into liposomes

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