Discovery of Novel Ionizable Lipids for Lipid Nanoparticles: Lipophilicity as a Predictor of Squaramide Head Group Lipid Clearance.

While we did not observe a clear trend correlating steric hindrance to clearance, when comparing α‐substituted and γ‐substituted tails across different cLogP values, our results implied that this effect is most pronounced in less lipophilic lipids, where a more hydrophilic environment permits greater enzymatic access to the ester bond.

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