01995nas a2200169   4500008004100000022001400041245013600055210006900191260000800260300001600268490000700284520133200291100002001623700002701643700002601670856012901696       2025                        eng d  a2470-134300aInvestigating the design of ssPalmO-derived lipid nanoparticles for mRNA delivery applications using molecular dynamics simulations0 aInvestigating the design of ssPalmOderived lipid nanoparticles f  cDEC  a61256-612670 v103 a<p>
	The rational design of lipid nanoparticles (LNPs) is essential for the effective transport of drugs and genetic material, as their structural and dynamic properties are heavily influenced by lipid composition and functional group modifications. In this study, we employed molecular dynamics simulations with density functional theory (DFT) derived force fields to investigate the bilayer properties of ssPalmO lipids, their phenyl ester (ssPalmO-phe) and benzyl ester (ssPalmO-ben) derivatives, as well as their cis and trans isomers. While all systems formed stable bilayers, cis-ssPalmO deviated by adopting a flexible, nonlamellar architecture. Trans isomers of ssPalmO-phe and ssPalmO-ben exhibited greater bilayer thickness, packing density, and order parameters due to stronger intramolecular chain interactions, while their aromatic substituents reduced lateral diffusion relative to ssPalmO. Trans isomers exhibited lower electrostatic potential differences, which increased upon incorporation of helper lipids, concomitantly enhancing bilayer packing and thickness while suppressing diffusion. These results clarify how lipid functionalization, stereochemistry, and helper lipid composition modulate bilayer organization, offering molecular level guidance for rational LNP design in drug and mRNA delivery.</p>
1 aBarange, Anjana1 aLuwang, Meitram, Niraj1 aMeena, Santosh, Kumar  uhttps://library.ncl.res.in/content/investigating-design-sspalmo-derived-lipid-nanoparticles-mrna-delivery-applications-using