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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
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Polyglycerol-Based Lipids: A Next-Generation Alternative to PEG in Lipid Nanoparticles for Advanced Drug Delivery
Yara Ensminger1, Rashmi Rashmi1, Michael Karimov2
1Institute For Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Macromolecular Rapid Communications
|September 16, 2025
Summary
Linear polyglycerol (lPG) offers an alternative to polyethylene glycol (PEG) in lipid nanoparticles (LNPs) for mRNA delivery. lPG-functionalized LNPs avoid anti-PEG antibodies, maintaining transfection efficiency comparable to PEGylated systems.
Area of Science:
- Biotechnology
- Nanomedicine
- Polymer Chemistry
Background:
- Polyethylene glycol (PEG) is a common polymer used in drug delivery systems like lipid nanoparticles (LNPs) to evade the immune system, providing a 'stealth' effect.
- However, the rising prevalence of anti-PEG antibodies in patients can trigger adverse immune responses and rapid clearance of PEGylated therapeutics, limiting their effectiveness.
- Lipid nanoparticles (LNPs) are crucial for delivering nucleic acids, with significant therapeutic potential demonstrated by mRNA vaccines.
Purpose of the Study:
- To develop and evaluate linear polyglycerol (lPG) as a non-immunogenic stealth polymer alternative to PEG in LNPs.
- To assess the ability of lPG-functionalized LNPs to deliver mRNA while avoiding immune reactions associated with anti-PEG antibodies.
- To compare the mRNA transfection efficiency of lPG-LNPs with traditional PEG-LNPs.
Main Methods:
- Formulation of lipid nanoparticles (LNPs) incorporating linear polyglycerol (lPG) as a surface coating.
- Evaluation of the binding affinity of lPG-functionalized LNPs to IgG anti-PEG antibodies.
- Assessment of mRNA (eGFP) delivery and transfection efficiency in HepG2 cells using lPG-LNPs compared to PEG-LNPs.
Main Results:
- lPG-functionalized LNPs exhibited negligible binding to IgG anti-PEG antibodies, indicating reduced immunogenicity.
- Successful delivery of enhanced green fluorescent protein (eGFP) mRNA into HepG2 cells was achieved using lPG-LNPs.
- The mRNA transfection efficiency of lPG-LNPs was comparable to that of PEGylated LNPs.
Conclusions:
- Linear polyglycerol (lPG) serves as a viable alternative to polyethylene glycol (PEG) in LNP formulations for mRNA delivery.
- lPG-functionalization of LNPs effectively mitigates immune responses related to anti-PEG antibodies.
- lPG-based LNPs demonstrate promising potential for safe and efficient nucleic acid delivery in therapeutic applications.
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