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European Journal of Pharmaceutics and Biopharmaceutics
Volume 171, 2022, Pages 80-89

Quantifying the heterogeneity of enzymatic dePEGylation of liposomal nanocarrier systems

Rasmus Eliasena,1, Thomas Lars Andresena,b, Jannik Bruun Larsena,b

Center for Nanomedicine and Theranostics, Department of Health Technology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.

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.

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