A combination drug delivery system employing thermosensitive liposomes for enhanced cell penetration and improved in vitro efficacy

Kleopatra Eleftheriou; Archontia Kaminari; Katerina N. Panagiotaki; Zili Sideratou; Michael Zachariadis; Jane Anastassopoulou; Dimitris Tsiourvas

doi:10.1016/j.ijpharm.2019.118912

A combination drug delivery system employing thermosensitive liposomes for enhanced cell penetration and improved in vitro efficacy

Kleopatra Eleftheriou, Archontia Kaminari, Katerina N. Panagiotaki, Zili Sideratou, Michael Zachariadis, Jane Anastassopoulou, Dimitris Tsiourvas

Research output: Contribution to journal › Article › peer-review

14 Citations (SciVal)

Abstract

Drug-loaded thermosensitive liposomes are investigated as drug delivery systems in combination with local mild hyperthermia therapy due to their capacity to release their cargo at a specific temperature range (40–42 °C). Additional benefit can be achieved by the development of such systems that combine two different anticancer drugs, have cell penetration properties and, when heated, release their drug payload in a controlled fashion. To this end, liposomes were developed incorporating at low concentration (5 mol%) a number of monoalkylether phosphatidylcholine lipids, encompassing the platelet activating factor, PAF, and its analogues that induce thermoresponsiveness and have anticancer biological activity. These thermoresponsive liposomes were efficiently (>90%) loaded with doxorubicin (DOX), and their thermal properties, stability and drug release were investigated both at 37 ^◦C and at elevated temperatures. In vitro studies of the most advantageous liposomal formulation containing the methylated PAF derivative (methyl-PAF, edelfosine), an established antitumor agent, were performed on human prostate cancer cell lines. This system exhibits controlled release of DOX at 40–42 °C, enhanced cell uptake due to the presence of methyl-PAF, and improved cell viability inhibition due to the combined action of both medications.

Original language	English
Article number	118912
Journal	International Journal of Pharmaceutics
Volume	574
DOIs	https://doi.org/10.1016/j.ijpharm.2019.118912
Publication status	Published - 25 Jan 2020

Bibliographical note

Funding Information:
K. N. P. acknowledges financial support from the Greek State Scholarships Foundation , program “Enhancement of human scientific resources through implementation of PhD research” with resources of the European program “Development of human resources, Education and lifelong learning”, 2014-2010 , co-funded by the European Social Fund and Greek State . A. K. acknowledges financial support from the project MIS 5002567 implemented under the “Action for the Strategic Development on the Research and Technological Sector”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” ( NSRF 2014-2020 ) and co-financed by GSRT Greece and the European Union (European Regional Development Fund) . This work was partially supported by the internal project No EE11968, entitled “Synthesis and characterization of nanostructured materials for environmental applications”. Appendix A

Funding Information:
K. N. P. acknowledges financial support from the Greek State Scholarships Foundation, program ?Enhancement of human scientific resources through implementation of PhD research? with resources of the European program ?Development of human resources, Education and lifelong learning?, 2014-2010, co-funded by the European Social Fund and Greek State. A. K. acknowledges financial support from the project MIS 5002567 implemented under the ?Action for the Strategic Development on the Research and Technological Sector?, funded by the Operational Programme ?Competitiveness, Entrepreneurship and Innovation? (NSRF 2014-2020) and co-financed by GSRT Greece and the European Union (European Regional Development Fund). This work was partially supported by the internal project No EE11968, entitled ?Synthesis and characterization of nanostructured materials for environmental applications?.

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

Eldefosine
Hyperthermia
Lysolipids
PAF analogues
Thermosensitive liposomes

ASJC Scopus subject areas

Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijpharm.2019.118912

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title = "A combination drug delivery system employing thermosensitive liposomes for enhanced cell penetration and improved in vitro efficacy",

abstract = "Drug-loaded thermosensitive liposomes are investigated as drug delivery systems in combination with local mild hyperthermia therapy due to their capacity to release their cargo at a specific temperature range (40–42 °C). Additional benefit can be achieved by the development of such systems that combine two different anticancer drugs, have cell penetration properties and, when heated, release their drug payload in a controlled fashion. To this end, liposomes were developed incorporating at low concentration (5 mol%) a number of monoalkylether phosphatidylcholine lipids, encompassing the platelet activating factor, PAF, and its analogues that induce thermoresponsiveness and have anticancer biological activity. These thermoresponsive liposomes were efficiently (>90%) loaded with doxorubicin (DOX), and their thermal properties, stability and drug release were investigated both at 37 ◦C and at elevated temperatures. In vitro studies of the most advantageous liposomal formulation containing the methylated PAF derivative (methyl-PAF, edelfosine), an established antitumor agent, were performed on human prostate cancer cell lines. This system exhibits controlled release of DOX at 40–42 °C, enhanced cell uptake due to the presence of methyl-PAF, and improved cell viability inhibition due to the combined action of both medications.",

keywords = "Eldefosine, Hyperthermia, Lysolipids, PAF analogues, Thermosensitive liposomes",

author = "Kleopatra Eleftheriou and Archontia Kaminari and Panagiotaki, {Katerina N.} and Zili Sideratou and Michael Zachariadis and Jane Anastassopoulou and Dimitris Tsiourvas",

note = "Funding Information: K. N. P. acknowledges financial support from the Greek State Scholarships Foundation , program “Enhancement of human scientific resources through implementation of PhD research” with resources of the European program “Development of human resources, Education and lifelong learning”, 2014-2010 , co-funded by the European Social Fund and Greek State . A. K. acknowledges financial support from the project MIS 5002567 implemented under the “Action for the Strategic Development on the Research and Technological Sector”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” ( NSRF 2014-2020 ) and co-financed by GSRT Greece and the European Union (European Regional Development Fund) . This work was partially supported by the internal project No EE11968, entitled “Synthesis and characterization of nanostructured materials for environmental applications”. Appendix A Funding Information: K. N. P. acknowledges financial support from the Greek State Scholarships Foundation, program ?Enhancement of human scientific resources through implementation of PhD research? with resources of the European program ?Development of human resources, Education and lifelong learning?, 2014-2010, co-funded by the European Social Fund and Greek State. A. K. acknowledges financial support from the project MIS 5002567 implemented under the ?Action for the Strategic Development on the Research and Technological Sector?, funded by the Operational Programme ?Competitiveness, Entrepreneurship and Innovation? (NSRF 2014-2020) and co-financed by GSRT Greece and the European Union (European Regional Development Fund). This work was partially supported by the internal project No EE11968, entitled ?Synthesis and characterization of nanostructured materials for environmental applications?. Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

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AU - Zachariadis, Michael

AU - Anastassopoulou, Jane

AU - Tsiourvas, Dimitris

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A combination drug delivery system employing thermosensitive liposomes for enhanced cell penetration and improved in vitro efficacy

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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