Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines

Abstract Liposomal drug delivery relies on polyethylene glycol (PEG) coating since it is essential for preserving the stability and increasing the plasma half-life of the lipid-based nanocarriers, and therefore it represents a critical quality attribute of nanomedicine formulations. Due to the compl...

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Main Authors: Francesco Fumagalli, Alexander Welle, Guillaume Bucher, Silvia Appleton, Jessica Ponti, Giacomo Ceccone, Luigi Calzolai, Dora Mehn
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03947-z
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author Francesco Fumagalli
Alexander Welle
Guillaume Bucher
Silvia Appleton
Jessica Ponti
Giacomo Ceccone
Luigi Calzolai
Dora Mehn
author_facet Francesco Fumagalli
Alexander Welle
Guillaume Bucher
Silvia Appleton
Jessica Ponti
Giacomo Ceccone
Luigi Calzolai
Dora Mehn
author_sort Francesco Fumagalli
collection DOAJ
description Abstract Liposomal drug delivery relies on polyethylene glycol (PEG) coating since it is essential for preserving the stability and increasing the plasma half-life of the lipid-based nanocarriers, and therefore it represents a critical quality attribute of nanomedicine formulations. Due to the complexity of their therapeutic action and the implications if they prove to be ineffective, decision-making in nanomedicine development requires statistically meaningful correlations between design principles and their biophysical properties. Precise characterization of PEG functional coatings is essential for quality control of PEGylated liposomes, it is required not only to measure the total amount of nanoparticle incorporated PEG-chains but also their abundance and conformation at the nanoparticle external surface. In this study, we developed a methodology to characterize PEG-coatings of PEGylated liposomes using a cryogenic protocol for time-of-flight secondary ions mass spectrometry (ToF-SIMS). The method was applied to liposomes formulated with varying PEG-lipid contents in the formulation and the measurements successfully distinguished PEGylated liposomes based on their PEG-lipid content in the liposome outer membranes. These results indicate that the cryogenic ToF-SIMS method could be potentially used to control the quality of PEGylated liposomes not only for research and but also for drug manufacturing processes.
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spelling doaj-art-6bc5f976e25643bcb232993fdcfda93e2025-08-20T03:04:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-03947-zSecondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicinesFrancesco Fumagalli0Alexander Welle1Guillaume Bucher2Silvia Appleton3Jessica Ponti4Giacomo Ceccone5Luigi Calzolai6Dora Mehn7European Commission, Joint Research Centre (JRC)Karlsruhe Nano Micro Facility (KNMF), Karlsruhe Institute of Technology (KIT)European Commission, Joint Research Centre (JRC)European Commission, Joint Research Centre (JRC)European Commission, Joint Research Centre (JRC)European Commission, Joint Research Centre (JRC)European Commission, Joint Research Centre (JRC)European Commission, Joint Research Centre (JRC)Abstract Liposomal drug delivery relies on polyethylene glycol (PEG) coating since it is essential for preserving the stability and increasing the plasma half-life of the lipid-based nanocarriers, and therefore it represents a critical quality attribute of nanomedicine formulations. Due to the complexity of their therapeutic action and the implications if they prove to be ineffective, decision-making in nanomedicine development requires statistically meaningful correlations between design principles and their biophysical properties. Precise characterization of PEG functional coatings is essential for quality control of PEGylated liposomes, it is required not only to measure the total amount of nanoparticle incorporated PEG-chains but also their abundance and conformation at the nanoparticle external surface. In this study, we developed a methodology to characterize PEG-coatings of PEGylated liposomes using a cryogenic protocol for time-of-flight secondary ions mass spectrometry (ToF-SIMS). The method was applied to liposomes formulated with varying PEG-lipid contents in the formulation and the measurements successfully distinguished PEGylated liposomes based on their PEG-lipid content in the liposome outer membranes. These results indicate that the cryogenic ToF-SIMS method could be potentially used to control the quality of PEGylated liposomes not only for research and but also for drug manufacturing processes.https://doi.org/10.1038/s41598-025-03947-zNanomedicinesLipid-based nanoparticlesSurface propertiesAdvanced functional coatingsPEGCryogenic methods
spellingShingle Francesco Fumagalli
Alexander Welle
Guillaume Bucher
Silvia Appleton
Jessica Ponti
Giacomo Ceccone
Luigi Calzolai
Dora Mehn
Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
Scientific Reports
Nanomedicines
Lipid-based nanoparticles
Surface properties
Advanced functional coatings
PEG
Cryogenic methods
title Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
title_full Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
title_fullStr Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
title_full_unstemmed Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
title_short Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
title_sort secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines
topic Nanomedicines
Lipid-based nanoparticles
Surface properties
Advanced functional coatings
PEG
Cryogenic methods
url https://doi.org/10.1038/s41598-025-03947-z
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