Microporosity, pore size and diffusional path length modulate lipolysis kinetics of triglycerides adsorbed into SBA-15 mesoporous silica particles.

Understanding lipase-mediated hydrolysis mechanisms within solid-state nanocarriers is fundamental for the rational design of lipid-based formulations. In this study, SBA-15 ordered mesoporous silica (MPS) particles were engineered with well-controlled nanostructural properties to systematically elucidate the role of intrawall microporosity, mesopore size and particle structure on lipase activity. Microporosity and diffusional path length were shown to be key modulators for lipase-provoked hydrolysis of medium chain triglycerides (MCT) confined within MPS, with small changes in pore size, between 9-13 nm, showing now clear correlation to lipase activity. Lipid speciation within MPS after lipolysis, obtained through 1H NMR, indicated that free fatty acids preferentially adsorbed to rod-shaped MPS (RodMPS) particles with high microporosity. MPS that formed aggregated spindle-like structures (AggMPS) had intrinsically reduced microporosity, which was hypothesised to limit lipase/lipid diffusion to and from the MPS pores and thus, retard lipolysis kinetics. A linear correlation between microporosity and the extent of lipase-provoked hydrolysis was observed within both AggMPS and RodMPS; ultimately indicating that the intricate interplay between microporosity and lipid/lipase diffusion can be harnessed to optimise lipolysis kinetics for silica-lipid hybrid carriers. The new insights derived in this study are integral to the future development of solid-state lipid-based nanocarriers that control lipase activity for improving the absorption of poorly soluble bioactive compounds.