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The surface of nanoparticles for pharmaceutical use is crucial, as it is the first interface that interacts with the biological environment in the body and therefore determines the fate of the nanoparticle itself. Aware of its key role, regulatory agencies urgently require rigorous quality control of the surface, including polyethylene glycol (PEG) coatings, a component widely used in nanomedicine, which is also present in the recent vaccines against SARS-CoV-2, to ensure efficacy and safety. Building on a review of the literature and experimental testing, this study proposes a workflow to overcome critical issues related to liposome PEG coating. It integrates microfluidic synthesis with PEG post-insertion, using mild incubation conditions and a straightforward quality control analysis for method efficiency and reliability. Using multi-detector Asymmetric-Flow Field-Flow Fractionation (AF4-MD) in combination with High-Performance Liquid Chromatography coupled to a Charged Aerosol Detector (HPLC-CAD) proved to be an efficient strategy for analyzing simultaneously both the size distribution and other size-dependent parameters with special attention on the precise composition of PEGylated liposomes. By exploiting the AF4 size separation of PEGylated liposomes from unincorporated PEG-lipid micelles, this approach enables the optimization of post-insertion reaction conditions and the validation of traditional purification methods. This comprehensive workflow allows for in-depth liposome characterization, focusing on critical quality attributes. It includes reliable and straightforward PEG coating determination, essential for post-insertion tuning, and offers potential adaptability to other stealth coatings, thus providing a valuable reference for nanomedicine developers, control laboratories, and regulatory bodies.
2026-08-13
AMER CHEMICAL SOC
JRC145071
1520-6882 (online),   
https://pubs.acs.org/ancham/article-pdf/98/26/19427/65230653/acs.analchem.5c07710.pdf,    https://doi.org/10.1021/acs.analchem.5c07710,    https://publications.jrc.ec.europa.eu/repository/handle/JRC145071,   
10.1021/acs.analchem.5c07710 (online),   
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