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PEGylated nanoemulsions containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol induced weakened accelerated blood clearance phenomenon

Abstract

Injections of polyethylene glycol (PEG)-modified nanomedicines can lead to an accelerated clearance of the next dose of PEGylated nanomedicines, which is referred to as the accelerated blood clearance (ABC) phenomenon. It has been reported that anti-PEG IgM plays an important role in the induction of the ABC phenomenon, identifying the interface between the main chain of PEG and the hydrophobic segment of the repeated injections of the PEGylated nanocarriers, resulting in increased liver uptake and loss of long-cycle characteristics. In this study, we demonstrated that the 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) in PEGylated nanoemulsions (PEs) may mask this interface between the main chain of PEG and the hydrophobic segment, inhibiting the recognition and binding of anti-PEG IgM to PEs, and evidently weakening the ABC phenomenon of PEs. This will provide a novel strategy to improve the curative effect of PEGylated nanocarriers.

Graphical abstract

PEGylated nanoemulsions (PEs) with 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) induced weakened the accelerated blood clearance (ABC) phenomenon in Wistar rats during repeated injection of PEs.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81973271).

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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Zhe Li, Xin Gao, and Xinyang Yan. The first draft of the manuscript was written by Zhe Li and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Haiying Ma.

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Li, Z., Gao, X., Yan, X. et al. PEGylated nanoemulsions containing 1,2-distearoyl-sn-glycero-3-phosphoglycerol induced weakened accelerated blood clearance phenomenon. Drug Deliv. and Transl. Res. 12, 2569–2579 (2022). https://doi.org/10.1007/s13346-021-01111-4

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  • DOI: https://doi.org/10.1007/s13346-021-01111-4

Keywords

  • PEGylated emulsions
  • 1,2-Distearoyl-sn-glycero-3-phosphoglycerol
  • Accelerated blood clearance phenomenon