Polyethylene glycol (PEG) as a broad applicability marker for LC–MS/MS-based biodistribution analysis of nanomedicines
Polyethylene glycol (PEG) conjugation (PEGylation) is a well-established strategy to improve the pharmacokinetic and biocompatibility properties of a wide variety of nanomedicines and therapeutic peptides and proteins. This broad use makes PEG an attractive ‘allround’ candidate marker for the biodis...
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Published in | Journal of controlled release Vol. 366; pp. 611 - 620 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
01.02.2024
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Polyethylene glycol (PEG) conjugation (PEGylation) is a well-established strategy to improve the pharmacokinetic and biocompatibility properties of a wide variety of nanomedicines and therapeutic peptides and proteins. This broad use makes PEG an attractive ‘allround’ candidate marker for the biodistribution of such PEGylated compounds. This paper presents the development of a novel strategy for PEG quantification in biological matrices. The methodology is based on sample hydrolysis which both decomposes the sample matrix and degrades PEGylated analytes to specific molecular fragments more suitable for detection by LC–MS/MS. Method versatility was demonstrated by applying it to a wide variety of PEGylated compounds, including polymeric poly(ethylbutyl cyanoacrylate) (PEBCA) nanoparticles, lipidic nanoparticles (Doxil®, LipImage 815™ and lipid nanoparticles for nucleic acid delivery) and the antibody Cimzia®. Method applicability was assessed by analyzing plasma and tissue samples from a comprehensive drug biodistribution study in rats, of both PEBCA and LipImage 815™ nanoparticles. The results demonstrated the method's utility for biodistribution studies on PEG. Importantly, by using the method described herein in tandem with quantification of nanoparticle payloads, we showed that this approach can provide detailed understanding of various critical aspects of the in vivo behavior of PEGylated nanomedicines, such as drug release and particle stability. Together, the presented results demonstrate the novel method as a robust, versatile and generic approach for biodistribution analysis of PEGylated therapeutics.
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•PEGylation is widely used to improve pharmacological properties of medicines.•Our method uses detection of PEG to describe biodistribution of nanomedicines.•We demonstrate that PEG detection improves understanding of biodistribution.•The analytical concept is generic and can apply to non-endogenous PEG alternatives. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Journal of Controlled Release |
ISSN: | 0168-3659 1873-4995 1873-4995 |
DOI: | 10.1016/j.jconrel.2024.01.016 |