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. 2023 May 10;34(6):941–960. doi: 10.1021/acs.bioconjchem.3c00174

Table 3. Effect of the Lipid Composition and Properties on the PEGylated LNPs Immune-Mediated Adverse Effects and Activity.

structural parameters/factors immune-mediated adverse effects/safety/activity aspects
LNP Composition and Parameters
lipid composition •cholesterol as a helper lipid suppresses protein binding and improves circulation time; it is also essential to particle stability113,166
•high cholesterol percentage in the bilayer membrane (≥70%) causes higher complement activation167
•phosphatidylcholines such as DSPC as helper lipids improve endocytosis of LNPs; substituting DSPC with the unsaturated DOPC and SOPC causes enhanced particle uptake and intracellular delivery113,164,168
size and surface charge •a rise in the PEG–lipid molar part from 1% to 5% correlates with significantly smaller LNPs163,164
•increased vesicle size and polydispersity of large multilamellar liposomes enhance pulmonary hypertensive response, while small unilamellar, monodisperse liposomes had no significant vasoactivity160
•anionic PEG–lipids undergo a drop in particle size with increasing PEG size and molar ratios in the LNPs169
•PEGylated carriers comprising negatively charged phospholipids stimulate complement activation stronger than neutral vesicles127
•the effect of particle size on LNP immunogenicity is controversial and requires further investigations15