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Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells

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Mixed PEGylated surfactant modifying system decrease the accelerated blood clearance phenomenon of nanoemulsions in

Yuqing Su¹, Wenya Tang², Yanzhi Song¹

¹School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, China.

Asian Journal of Pharmaceutical Sciences

|February 28, 2020

Summary

Repeated use of poly (ethylene glycol) (PEG)-coated carriers causes accelerated blood clearance (ABC). A new 4-arm PEG-cholesteryl conjugate (4-arm PEG-CHMA) in nanoemulsions reduced this immune response, offering a promising drug delivery system.

Keywords:

4-arm PEG5000-CHMA Accelerated blood clearance (ABC) phenomenon Anti-PEG IgM Repeated administration

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Area of Science:

Nanotechnology
Immunology
Pharmacology

Background:

Poly (ethylene glycol) (PEG)-coated carriers can induce an accelerated blood clearance (ABC) phenomenon, limiting their therapeutic potential.
This immunological response presents a significant challenge for drug delivery systems relying on PEGylated nanoparticles.
Developing strategies to mitigate ABC is crucial for advancing nanomedicine.

Purpose of the Study:

To synthesize and characterize a novel 4-arm poly (ethylene glycol-5000) cholesteryl methyl amide (4-arm PEG5000-CHMA).
To investigate the pharmacokinetic profile and ABC phenomenon of tocopheryl nicotinate (TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and/or mPEG2000-DSPE.
To evaluate the potential of these novel nanoemulsions in reducing the ABC phenomenon for improved drug delivery.

Main Methods:

Synthesis and structural confirmation of 4-arm PEG5000-CHMA using IR and 1H-NMR spectroscopy.
Preparation and characterization of tocopheryl nicotinate (TN)-loaded nanoemulsions with different PEGylation strategies.
Pharmacokinetic studies in rats, measuring plasma levels of TN and anti-PEG IgM antibodies via HPLC and ELISA to assess the ABC phenomenon.

Main Results:

The novel 4-arm PEG5000-CHMA was successfully synthesized and characterized.
Nanoemulsions co-modified with 4-arm PEG5000-CHMA and mPEG2000-DSPE (CPNEs) demonstrated comparable circulation times to mPEG2000-DSPE alone.
CPNEs significantly reduced the accelerated blood clearance (ABC) phenomenon compared to traditional PEGylated nanoemulsions.

Conclusions:

The novel 4-arm PEG5000-CHMA is an effective component for modifying nanoemulsions.
Coating nanoemulsions with both 4-arm PEG5000-CHMA and mPEG2000-DSPE can successfully mitigate the accelerated blood clearance (ABC) phenomenon.
These findings present a promising strategy for developing clinically viable nanoemulsions for therapeutic and imaging applications.