Enhancing electroporation-induced liposomal drug release in suspension and solid phases

Abby Silbaugh; Joseph Vallin; Francisco Pelaez; Mihee Kim; Qi Shao; Hanseung Lee; John C. Bischof; Samira M. Azarin

doi:10.1016/j.ijpharm.2023.122744

Enhancing electroporation-induced liposomal drug release in suspension and solid phases

Abby Silbaugh, Joseph Vallin, Francisco Pelaez, Mihee Kim, Qi Shao, Hanseung Lee, John C. Bischof, Samira M. Azarin

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

1 Scopus citations

Abstract

When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.

Original language	English (US)
Article number	122744
Journal	International journal of pharmaceutics
Volume	635
DOIs	https://doi.org/10.1016/j.ijpharm.2023.122744
State	Published - Mar 25 2023

Bibliographical note

Funding Information:
This study was supported by the Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., NSF CBET-1845366, NIH T32GM008347 (J.V.), and the University of Minnesota’s Office of Undergraduate Research (A.S.).

Funding Information:
The authors would like to thank Prof. Joseph Zasadzinski for his helpful assistance with Cryo-SEM analysis and discussion of the effects of liposomal composition on membrane lysis. Portions of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. Specifically, the Hitachi SU8320 cryo-SEM and cryospecimen preparation system were provided by NSF MRI DMR-1229263. Other portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) under Award Number ECCS-2025124.

Publisher Copyright:
© 2023 Elsevier B.V.

Keywords

Electroporation
Liposome
Membrane fluidity
On-demand drug delivery
Polymer scaffold
Thermal stability

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10.1016/j.ijpharm.2023.122744

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title = "Enhancing electroporation-induced liposomal drug release in suspension and solid phases",

abstract = "When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.",

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author = "Abby Silbaugh and Joseph Vallin and Francisco Pelaez and Mihee Kim and Qi Shao and Hanseung Lee and Bischof, {John C.} and Azarin, {Samira M.}",

note = "Funding Information: This study was supported by the Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., NSF CBET-1845366, NIH T32GM008347 (J.V.), and the University of Minnesota{\textquoteright}s Office of Undergraduate Research (A.S.). Funding Information: The authors would like to thank Prof. Joseph Zasadzinski for his helpful assistance with Cryo-SEM analysis and discussion of the effects of liposomal composition on membrane lysis. Portions of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. Specifically, the Hitachi SU8320 cryo-SEM and cryospecimen preparation system were provided by NSF MRI DMR-1229263. Other portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) under Award Number ECCS-2025124. Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

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AU - Silbaugh, Abby

AU - Vallin, Joseph

AU - Pelaez, Francisco

AU - Kim, Mihee

AU - Shao, Qi

AU - Lee, Hanseung

AU - Bischof, John C.

AU - Azarin, Samira M.

N1 - Funding Information: This study was supported by the Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., NSF CBET-1845366, NIH T32GM008347 (J.V.), and the University of Minnesota’s Office of Undergraduate Research (A.S.). Funding Information: The authors would like to thank Prof. Joseph Zasadzinski for his helpful assistance with Cryo-SEM analysis and discussion of the effects of liposomal composition on membrane lysis. Portions of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. Specifically, the Hitachi SU8320 cryo-SEM and cryospecimen preparation system were provided by NSF MRI DMR-1229263. Other portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) under Award Number ECCS-2025124. Publisher Copyright: © 2023 Elsevier B.V.

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N2 - When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.

AB - When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.

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KW - Membrane fluidity

KW - On-demand drug delivery

KW - Polymer scaffold

KW - Thermal stability

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ER -

Enhancing electroporation-induced liposomal drug release in suspension and solid phases

Abstract

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