Characterization of colloidal structures during intestinal lipolysis using small-angle neutron scattering

Abstract

Hypothesis Bile micelles are thought to mediate intestinal absorption, in part by providing a phase into which compounds can partition. Solubilizing capacity of bile micelles is enhanced during the digestion of fat rich food. We hypothesized that the intestinal digestion of triglycerides causes an increase in volume of micelles that can be quantitatively monitored over the course of digestion using small-angle neutron scattering (SANS), and that SANS can enable evaluation of the contribution of each of the components present during digestion to the size of micelles. Experiments SANS was used to characterize the size and shape of micelles present prior to and during the in vitro simulated intestinal digestion of a model food-associated lipid, triolein. Findings Pre-lipolysis mixtures of a bile salt and phospholipid simulating bile concentrations in fed conditions were organized in micelles with an average volume of 40 nm3. During lipolysis, the micelle volume increased 2.5-fold over a 2-hour digestion period due to growth in one direction as a result of insertion of monoglycerides and fatty acids. These efforts represent a basis for quantitative mechanistic understanding of changes in solubilizing capacity of the intestinal milieu upon ingestion of a fat-rich meal.

Mechanistic studies and modeling of the impact of food on oral drug absorption

“…It should be noted that the micelles investigated here could also be cylindrical in shape, making the cylinder model also a plausible fitting model. In a previous study, we have shown that for the micelles investigated here the micellar volume does not change as a function of shape model chosen [152]. The micelle volume is the critical parameter in investigating drug partitioning into the micelle phase, rather than the micelle dimensions.…”

“…is the total micellar volume per unit solution volume, is the total number of micelles per unit solution volume, 0, is the volume of one micelle in the absence of FA, and are the concentration of MO and OA molecules present in micelles as a function of aqueous bulk volume, respectively, is the Avogadro number, and Ṽ and Ṽ are the volume of one MO and OA molecule, respectively. The average number of micelles per unit solution volume for the specific composition and concentration of bile components and the average volume of one micelle in the absence of MG and FA have been determined previously to be 1.03 x 10 17 micelles/mL and 40 nm 3 [152].…”

“…SANS measurements were performed using the GP-SANS at the High Flux Isotope Reactor in Oak Ridge National Labs, TN, USA. Measurements, data reduction, and scattering intensity profile fitting were performed as reported previously [152].…”

“…The bulk volume is approximated to the aqueous volume as the micellar volume was negligible ( = 4 µL/mL solution [152]). By substituting eqn 12 into 15, we obtain:…”

“…The micellar volume has been shown to increase in the presence of micelleassociated MO and OA [152]. Indeed, SANS studies of fed state micelles mixed with monoolein and oleic acid at various concentrations, respectively, allowed analysis of the neutron scattering intensity profiles in the medium-to-high Q range (0.01 < Q < 0.5 Å -1 )…”