pH‐Dependent Lyotropic Liquid Crystalline Mesophase and Ionization Behavior of Phytantriol‐Based Ionizable Lipid Nanoparticles

Jan 31, 2024Small (Weinheim an der Bergstrasse, Germany)

How pH Affects the Structure and Charge of Phytantriol-Based Ionizable Lipid Nanoparticles

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Abstract

Lipid nanoparticles (LNPs) with unique inverse mesostructures may enhance drug delivery capabilities.

LNPs are composed of ionizable lipids (ALC-0315 and SM-102) and a helper lipid (phytantriol).
Partial mesophase diagrams were generated for ALC-0315/PT and SM-102/PT LNPs based on lipid ratio and pH.
Evaluation of LNP stabilizers (Pluronic F127, Pluronic F108, and Tween 80) revealed their impact on phase behavior.
The study explores the physicochemical properties of LNPs, including size and mesophase state.
Findings may provide insights into the ionization state and self-assembled structures of LNPs.

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Self-assembled lipid nanoparticles (LNPs), serving as essential nanocarriers in recent COVID-19 mRNA vaccines, provide a stable and versatile platform for delivering a wide range of biological materials. Notably, LNPs with unique inverse mesostructures, such as cubosomes and hexosomes, are recognized as fusogenic nanocarriers in the drug delivery field. This study delves into the physicochemical properties, including size, lyotropic liquid crystalline mesophase, and apparent pKof LNPs with various lipid components, consisting of two ionizable lipids (ALC-0315 and SM-102) used in commercial COVID-19 mRNA vaccines and a well-known inverse mesophase structure-forming helper lipid, phytantriol (PT). Two partial mesophase diagrams are generated for both ALC-0315/PT LNPs and SM-102/PT LNPs as a function of two factors, ionizable lipid ratio (α, 0-100 mol%) and pH condition (pH 3-11). Furthermore, the impact of different LNP stabilizers (Pluronic F127, Pluronic F108, and Tween 80) on their pH-dependent phase behavior is evaluated. The findings offer insights into the self-assembled mesostructure and ionization state of the studied LNPs with potentially enhanced endosomal escape ability. This research is relevant to developing innovative next-generation LNP systems for delivering various therapeutics. a

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pH‐Dependent Lyotropic Liquid Crystalline Mesophase and Ionization Behavior of Phytantriol‐Based Ionizable Lipid Nanoparticles

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