Steric stabilizers inhibit or enhance enzymatic digestion depending on the internal nanostructure of lipid nanoparticles

Abstract Lipidic nanoparticles (LNPs), including liposomes and cubosomes, are widely employed drug delivery systems owing to their biocompatibility and capacity for stimuli-responsive ‘smart’ drug release. Steric stabilizers, including DSPE-PEG-2000 and Pluronic F127, are commonly used to stabilize LNPs by creating an effective steric barrier between the particle and aqueous physiological environment, but the implication for interactions with macromolecular components of complex physiological fluids is unclear. Thus, the impact of the polymeric steric barrier on enzymatic digestion by bacterial lipases is investigated in this study. Specifically, the impact of stabilizer chemistry, mode of attachment and nanoparticle geometry on the digestion of phospholipid liposomes and monoolein cubosomes by cell-free supernatants of Staphylococcus aureus and Pseudomonas aeruginosa containing the expressed extracellular enzymes from these organisms is investigated. Small-angle X-ray scattering (SAXS) revealed that bilayer-anchored DSPE-PEG-2000 hinders the digestion of phospholipid liposomes yet accelerates the digestion of monoolein cubosomes. These results suggest that nanoparticle architecture determines how effectively steric stabilizers protect against enzymatic digestion. This article is part of the theme issue ‘Geometry, materials and the imagination’.