PEG-Lipid Post Insertion into Drug Delivery Liposomes Quantified at the Single Liposome Level

Rasmus Eliasen, Thomas L. Andresen, Jannik B. Larsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Liposomal drug delivery systems are designed to avoid the body's natural clearance machinery and are typically achieved by incorporation lipid-anchored poly(ethylene glycol) (PEG) polymers. When preparing such liposomes it is intrinsically assumed that all available PEG-lipid is incorporated evenly into every liposome of a preparation, however this assumption remains unchallenged. Thus, a quantitative understanding of how PEG-lipid incorporation conditions affect the PEG density on individual liposomes can provide novel insights on how to optimize an important parameter of liposomal circulation kinetics and therapeutic efficacy. Here a sensitive fluorescence-based single liposome assay is employed that allows, for the first time, the quantification of the PEG-lipid density on individual liposomes. The assay is used to demonstrate that incubation time and temperature, liposome membrane lipid saturation state and PEG anchoring moiety all affect the effective PEG surface density. Furthermore, the unique ability of the assay to investigate single liposomes within the ensemble, allows to quantify significant variations in PEG surface density between individual liposomes. Thus, the assay provides crucial insights on how to improve both the overall PEG surface density and reduce the liposome-to-liposome variation, facilitating the design and development of more uniform, controllable, and efficacious PEG-lipid containing liposomal drug delivery systems.
Original languageEnglish
Article number1801807
JournalAdvanced Materials Interfaces
Volume6
Issue number9
Number of pages10
ISSN2196-7350
DOIs
Publication statusPublished - 2019

Cite this

@article{a7fc85b4bb6d4498919fba440e829d4e,
title = "PEG-Lipid Post Insertion into Drug Delivery Liposomes Quantified at the Single Liposome Level",
abstract = "Liposomal drug delivery systems are designed to avoid the body's natural clearance machinery and are typically achieved by incorporation lipid-anchored poly(ethylene glycol) (PEG) polymers. When preparing such liposomes it is intrinsically assumed that all available PEG-lipid is incorporated evenly into every liposome of a preparation, however this assumption remains unchallenged. Thus, a quantitative understanding of how PEG-lipid incorporation conditions affect the PEG density on individual liposomes can provide novel insights on how to optimize an important parameter of liposomal circulation kinetics and therapeutic efficacy. Here a sensitive fluorescence-based single liposome assay is employed that allows, for the first time, the quantification of the PEG-lipid density on individual liposomes. The assay is used to demonstrate that incubation time and temperature, liposome membrane lipid saturation state and PEG anchoring moiety all affect the effective PEG surface density. Furthermore, the unique ability of the assay to investigate single liposomes within the ensemble, allows to quantify significant variations in PEG surface density between individual liposomes. Thus, the assay provides crucial insights on how to improve both the overall PEG surface density and reduce the liposome-to-liposome variation, facilitating the design and development of more uniform, controllable, and efficacious PEG-lipid containing liposomal drug delivery systems.",
author = "Rasmus Eliasen and Andresen, {Thomas L.} and Larsen, {Jannik B.}",
year = "2019",
doi = "10.1002/admi.201801807",
language = "English",
volume = "6",
journal = "Advanced Materials Interfaces",
issn = "2196-7350",
publisher = "John Wiley & Sons Ltd",
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}

PEG-Lipid Post Insertion into Drug Delivery Liposomes Quantified at the Single Liposome Level. / Eliasen, Rasmus; Andresen, Thomas L.; Larsen, Jannik B.

In: Advanced Materials Interfaces, Vol. 6, No. 9, 1801807, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - PEG-Lipid Post Insertion into Drug Delivery Liposomes Quantified at the Single Liposome Level

AU - Eliasen, Rasmus

AU - Andresen, Thomas L.

AU - Larsen, Jannik B.

PY - 2019

Y1 - 2019

N2 - Liposomal drug delivery systems are designed to avoid the body's natural clearance machinery and are typically achieved by incorporation lipid-anchored poly(ethylene glycol) (PEG) polymers. When preparing such liposomes it is intrinsically assumed that all available PEG-lipid is incorporated evenly into every liposome of a preparation, however this assumption remains unchallenged. Thus, a quantitative understanding of how PEG-lipid incorporation conditions affect the PEG density on individual liposomes can provide novel insights on how to optimize an important parameter of liposomal circulation kinetics and therapeutic efficacy. Here a sensitive fluorescence-based single liposome assay is employed that allows, for the first time, the quantification of the PEG-lipid density on individual liposomes. The assay is used to demonstrate that incubation time and temperature, liposome membrane lipid saturation state and PEG anchoring moiety all affect the effective PEG surface density. Furthermore, the unique ability of the assay to investigate single liposomes within the ensemble, allows to quantify significant variations in PEG surface density between individual liposomes. Thus, the assay provides crucial insights on how to improve both the overall PEG surface density and reduce the liposome-to-liposome variation, facilitating the design and development of more uniform, controllable, and efficacious PEG-lipid containing liposomal drug delivery systems.

AB - Liposomal drug delivery systems are designed to avoid the body's natural clearance machinery and are typically achieved by incorporation lipid-anchored poly(ethylene glycol) (PEG) polymers. When preparing such liposomes it is intrinsically assumed that all available PEG-lipid is incorporated evenly into every liposome of a preparation, however this assumption remains unchallenged. Thus, a quantitative understanding of how PEG-lipid incorporation conditions affect the PEG density on individual liposomes can provide novel insights on how to optimize an important parameter of liposomal circulation kinetics and therapeutic efficacy. Here a sensitive fluorescence-based single liposome assay is employed that allows, for the first time, the quantification of the PEG-lipid density on individual liposomes. The assay is used to demonstrate that incubation time and temperature, liposome membrane lipid saturation state and PEG anchoring moiety all affect the effective PEG surface density. Furthermore, the unique ability of the assay to investigate single liposomes within the ensemble, allows to quantify significant variations in PEG surface density between individual liposomes. Thus, the assay provides crucial insights on how to improve both the overall PEG surface density and reduce the liposome-to-liposome variation, facilitating the design and development of more uniform, controllable, and efficacious PEG-lipid containing liposomal drug delivery systems.

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