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Polysorbate 80-containing ionizable lipid nanoparticles for mRNA delivery
Xuefeng Tang1, Shixiao Ding1, Shilin Yang1
1State Key Laboratory of Urban Water Resource and Environment, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China. hanxiaojun@hit.edu.cn.
Biomaterials Science
|September 19, 2024
Summary
Polysorbate 80 (PS80) offers a safer alternative to polyethylene glycol (PEG) in mRNA vaccine delivery systems. PS80-based nanoparticles show improved stealth, cell viability, and serum resistance, reducing toxic side effects.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery
Background:
- Ionizable lipid nanoparticles (iLNPs) are crucial for mRNA vaccine delivery.
- Polyethylene glycol (PEG) is a common iLNP component but can cause adverse immune reactions and reduce efficacy.
- Developing PEG-free iLNPs is essential for improving biosafety and therapeutic outcomes.
Purpose of the Study:
- To evaluate polysorbate 80 (PS80) as a PEG alternative in iLNPs for mRNA delivery.
- To assess the impact of PS80 on nanoparticle stealth, cellular uptake, and biosafety.
- To develop improved, PEG-free iLNPs for enhanced gene delivery applications.
Main Methods:
- Formulation of eGFP mRNA-loaded ionizable lipid nanoparticles with PS80 (PS80-iLNPs) and PEG (PEG-iLNPs).
- Assessment of nanoparticle stealth properties and resistance to serum interference.
- Evaluation of cell viability and cellular uptake efficiency of PS80-iLNPs versus PEG-iLNPs.
Main Results:
- PS80-iLNPs demonstrated enhanced stealthiness (1.14-fold increase) compared to PEG-iLNPs.
- PS80-iLNPs exhibited significantly higher cell viability (1.12 times) at 50 μg mL⁻¹ lipid concentration.
- PS80-iLNPs showed superior serum resistance, with only a 30.55% reduction in uptake versus 44.97% for PEG-iLNPs.
Conclusions:
- Polysorbate 80 (PS80) is a viable and effective alternative to polyethylene glycol (PEG) in ionizable lipid nanoparticles.
- PS80-iLNPs offer improved biosafety, stealth, and serum resistance for mRNA delivery.
- This study provides a strong foundation for developing next-generation, PEG-free mRNA delivery systems.
