A lipid toolbox of sugar alcohol fatty acid monoesters for single-component lipid nanoparticles with temperature-controlled release

This study aimed to prepare single-component LNPs with sugar alcohol fatty acid monoesters for temperaturecontrolled release. In total, 20 kinds of lipids with a series of sugar alcohol head groups (ethylene glycol, glycerol, erythritol, xylitol and sorbitol) and fatty acyl tails (12:0, 14:0, 16:0 and 18:0) were synthesised via lipase-catalysed esterification. Their physicochemical properties and upper/lower critical solution temperature (LCST/USCT) were analysed. Two groups of mixed lipids, 78 % ethylene glycol lauric acid monoester + 22 % sorbitol stearic acid monoester (LNP-1) and 90 % ethylene glycol lauric acid monoester + 10 % xylitol myristic acid monoester (LNP-2), had LCST/USCT of approximately 37 C, which formed empty LNPs using the emulsification-diffusion method. These two mixed lipids were prepared for LNPs loaded with curcumin, showing high encapsulation (>90 %), mean particle sizes of approximately 250 nm and low polydispersity index (& LE;0.2). These lipids have the potential for tailor-made LNPs achieving thermo-responsivity in delivering bioactive agents and drugs.