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Eur J Pharm Biopharm. 2022 Jan 09; doi: 10.1016/j.ejpb.2021.12.013. Epub 2022 Jan 09.

Quantifying the heterogeneity of enzymatic dePEGyaltion of liposomal nanocarrier systems.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Rasmus Eliasen, Thomas Lars Andresen, Jannik Bruun Larsen

Affiliations

  1. Center for Nanomedicine and Theranostics, Department of Health Technology, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark.
  2. Center for Nanomedicine and Theranostics, Department of Health Technology, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark. Electronic address: [email protected].
  3. Center for Nanomedicine and Theranostics, Department of Health Technology, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark. Electronic address: [email protected].

PMID: 35021105 DOI: 10.1016/j.ejpb.2021.12.013

Abstract

Lipid nanoparticles have been clinically successful in particular recently within the vaccine field, but better tools are needed to analyze heterogeneities at the single particle level to progress drug delivery designs to the next level. Especially, liposomal nanocarriers are becoming increasingly complex e.g. by employing environmental cues for shedding their protective PEG layer, however a detailed mechanistic understanding of how the dePEGylation varies from liposome-to-liposome is still missing. Here we present the development of a fluorescence microscopy based assay capable of detecting the enzyme mediated dePEGylation of individual liposomes. We employ this methodology to understand how enzyme type-, concentration- and incubation time, in addition to liposome size, affects the dePEGylation at the single particle level.

Copyright © 2021. Published by Elsevier B.V.

Keywords: Enzyme mediated dePEGylation; Liposomal nanocarriers; Liposome heterogeneity; Quantitative fluorescence microscopy; Single liposome measurements

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this pa

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