The Role of Porous Nanostructure in Controlling Lipase-Mediated Digestion of Lipid Loaded into Silica Particles

Abstract

The rate and extent of lipolysis, the breakdown of fat into molecules that can be absorbed into the bloodstream, depend on the interfacial composition and structure of lipid (fat) particles. A novel method for controlling the interfacial properties is to load the lipid into porous colloidal particles. We report on the role of pore nanostructure and surface coverage in controlling the digestion kinetics of medium-chain and long-chain triglycerides loaded into porous silica powders of different particle size, porosity, and hydrophobicity/hydrophilicity. An in vitro lipolysis model was used to measure digestion kinetics of lipid by pancreatic lipase, a digestive enzyme. The rate and extent of lipid digestion were significantly enhanced when a partial monolayer of lipid was loaded in porous hydrophilic silica particles compared to a submicrometer lipid-in-water emulsion or a coarse emulsion. The inhibitory effect of digestion products was clearly evident for digestion from a submicrometer emulsion and coarse emulsion. This effect was minimal, however, in the two silica-lipid systems. Lipase action was inhibited for lipid loaded in the hydrophobic silica and considered due to the orientation of lipase adsorption on the methylated silica surface. Thus, hydrophilic silica promotes enhanced digestion kinetics, whereas hydrophobic silica exerts an inhibitory effect on hydrolysis. Evaluation of digestion kinetics enabled the mechanism for enhanced rate of lipolysis in silica-lipid systems to be derived and detailed. These investigations provide valuable insights for the optimization of smart food microparticles and lipid-based drug delivery systems based on lipid excipients and porous nanoparticles.

Bioactive Hybrid Particles from Poly(d,l-lactide-co-glycolide) Nanoparticle Stabilized Lipid Droplets

“…As digestion proceeded, the rate of digestion was promptly inhibited due to the accumulation of interfacially active digestion products and lecithin on the emulsion droplet interface. 24 At high concentrations, or as the mean emulsion droplet size decreases, lecithin interferes with lipase adsorption by competing with the enzyme for sites on the oil-water interface. 42 In addition to this, at insufficient bile salt concentrations, digestion products (free fatty acids and monoglycerides), adsorb to the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 20 oil-water interface due to their amphiphilic structure.…”

“…First-order kinetics do not precisely describe the entire digestion profile of a submicron emulsion ( Figure 6, inset) due to the interference effect of digestion products causing a sharp decrease in reaction rate. 24 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 due to the difference in nanoparticle charge. The overall extents of lipolysis for 10 wt% and 50 wt% PLGA(-) nanoparticle-stabilized emulsions were 64.0 ± 3.6% and 55.8 ± 2.9%, respectively, compared to 78.9 ± 5.6% and 66.9 ± 5.1% for 10 wt% and 50 wt% PLGA(+) nanopartilce-stabilized emulsions, respectively.…”

“…[21][22][23] The increased interfacial surface area of lipid, binding support of hydrophilic silica and reduced interference effect of digestion products have shown to enhance lipase action in SLH microparticles. 24 However, the exact effect of surface chemistry of the solid matrix 5 support on the digestibility of the encapsulated lipid is not well understood. In addition to this, Yu et al 25 recently expressed concerns surrounding the in vivo biocompatibility and toxicity of silica nanoparticles with varying particle sizes, geometries and porosities.…”

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

“…Lipolysis kinetics was increased 4.5-fold when medium chain triglycerides were encapsulated in hydrophilic porous silica particles compared with a submicron emulsion. This was owing to a 5.1-fold increase in interfacial surface area [205]. In contrast, Tan et al described the ability of porous silica nanoparticles to inhibit the lipase activity when partially stabilizing the lipid phase at various concentrations [206].…”

Effects of starch addition on the activity and specificity of food‐grade lipases

“…However, there are significant differences in the nature and yield of the possible products of lipolytic reactions as a function of a number of parameters of practical relevance, which include: (i) the type and origin of the enzyme ; (ii) the nature of the fats undergoing hydrolysis [12]; (iii) the conditions used (i.e., the physicochemical environment in which the enzyme and its substrate(s) interact) . There are indications that the presence of particles in lipolytic reaction mixtures may affect the orientation of either the substrate or the enzyme or promote the formation of lipid micro‐ and nanostructures that affect rate and specificity of the enzyme action .…”