Effect of oil-droplet size on the oxidation of microencapsulated methyl linoleate.

Effects of oil-droplet size, the weight ratio of oil to wall material and the storage temperature on the oxidation of methyl linoleate microencapsulated with maltodextrin by spray-drying were examined. The oxidation of methyl linoleate was more retarded for the microcapsules prepared from the emulsion having smaller oil droplets. The oxidation was more suppressed for the microcapsules having a lower weight ratio of oil to wall material. The fraction of unoxidized methyl linoleate leveled off after 10- to 15-days storage. The level, Y(infinity), depended on the weight ratio. The dependence of Y(infinity) on the weight ratio was analyzed based on the percolation theory, and the three-dimensional model of the theory was suitable to express the dependence. The effect of the storage temperature on the oxidation of microencapsulated methyl linoleate was also examined, and the activation energy was evaluated. The value of the energy suggested that the oxidation itself was a rate-limiting step for the oxidation of methyl linoleate encapsulated with maltodextrin.

Effects of inner-phase components of water-in-oil-in-water emulsion on low-pH tolerance of Lactobacillus acidophilus incorporated into inner-water phase.

The incorporation of Lactobacillus acidophilus, which has a low acid tolerance, into the inner-water phase of water-in-oil-in-water (W/O/W) emulsion improved the bacterial survival rate in a model gastric juice. The components that enhanced the acid tolerance of the bacterium in W/O/W emulsion were investigated. Although the acid tolerance enhancement induced by the tested components was low at pH 2, some components significantly improved the tolerance at pH 4. In particular, the acid tolerance enhancement induced by yeast extract and sodium caseinate was marked.

Autoxidation of mono-, di-, and trilinoleoyl glycerols at different concentrations.

Mono-, di-, and trilinoleoyl glycerols were diluted with 1-undecanol or hexadecane to produce specific concentrations, and their oxidation processes were measured at 65 degrees C at 12% relative humidity. The rate constants for oxidation of the linoleoyl residue were proportional to the concentration for all substrates. This fact suggests that no intramolecular radical chain reaction between the linoleoyl residues occurred.

Suppressive effect of alkyl ferulate on the oxidation of linoleic acid.

The oxidation processes of linoleic acid in the presence of ferulic acid, and 1-pentyl, 1-hexyl and 1-heptyl ferulates were observed at various temperatures and different molar ratios of each additive to linoleic acid. The processes were analyzed based on a kinetic equation of the autocatalytic type to evaluate the oxidative rate constant, k, and the kinetic parameter, Y(0), by which the initiation period for the oxidation of linoleic acid was mainly governed. The k values for linoleic acid mixed with each of the alkyl ferulates were smaller than that for linoleic acid mixed with ferulic acid. The greater suppressive effect of the alkyl ferulates would be ascribable to their higher solubility in linoleic acid. Both the activation energy, E, and the frequency factor, k(0), for the oxidation of linoleic acid mixed with ferulic acid or pentyl ferulate decreased with increasing molar ratio of the additive to linoleic acid.

Hydrolysis of the oil phase of a W/O/W emulsion by pancreatic lipase.

W/O/W emulsions are expected to protect bioactive substances from degradation by pancreatic enzymes. We investigated the enzymatic hydrolysis of the oil phase and release of a marker substance from the inner-aqueous phase to the outer-aqueous phase using an artificial digestive fluid. Octanoic acid triacylglycerol (C8TG) was used as the oil phase. W/O/W emulsions were prepared by two-step homogenization and succeeding membrane filtration. When the artificial digestive fluid containing lipase and gall was added to the emulsion, release of the marker substance from the inner-phase solution, oil-phase hydrolysis, and emulsion coalescence occurred in that order. When a coarse emulsion and 0.2- and 0.8-microm membrane-filtered fine emulsions were treated with the fluid for 1 h, the degrees of C8TG hydrolysis were 3.8%, 55% and 57%, the fractions of the marker substance released from the inner-water phase were 2.7%, 89% and 72%, and the median diameters of the oil droplets were changed from 32 to 23 microm, 0.71 to 27 microm, and from 2.2 to 26 microm, respectively. These results suggested that the diameter of the oil droplets in the W/O/W emulsion significantly affected the release profile of the marker loaded in the inner-water phase of the emulsion.

Relationship between structure and permeability of dipeptide derivatives containing tryptophan and related compounds across human intestinal epithelial (Caco-2) cells.

The permeability of dipeptide derivatives containing tryptophans and indole derivatives through Caco-2 cells was used as an in vitro intestinal absorption model in order to clarify structural factors which influence their intestinal epithelial permeation and metabolism. Most peptide derivatives were hydrolysed not only by the cytosolic enzymes in Caco-2 cells during permeation but also by enzymes released to the apical solution before cell permeation. The N-terminal blocked dipeptides were more resistant to hydrolases expressed in the Caco-2 cells and indole derivatives were not entirely degraded. Based on compound concentration dependency and comparison of permeability coefficients in apical-to-basolateral and basolateral-to-apical directions, the main absorption mechanism of compounds were determined. Compounds were then classified into three groups; (1) passively transported compounds, (2) actively transported compounds and (3) compounds excreted by P-glycoprotein.

Relationships between structure and high-throughput screening permeability of peptide derivatives and related compounds with artificial membranes: application to prediction of Caco-2 cell permeability.

To evaluate absorption of compounds across the membrane via a transcellular route, the permeability of peptide derivatives and related compounds was measured by the parallel artificial membrane permeation assay (PAMPA). The permeability coefficients by PAMPA were analyzed quantitatively using classical QSAR and Volsurf approaches with the physicochemical parameters. The results from both approaches showed that hydrogen bonding ability of molecules in addition to hydrophobicity at a particular pH were significant in determining variations in PAMPA permeability coefficients. The relationship between Caco-2 cell permeability and artificial lipid membrane permeability was then determined. The compounds were sorted according to their absorption pathway in the plot of the Caco-2 cell and PAMPA permeability coefficients.

Anti-oxidant activity of acyl ascorbates in intestinal epithelial cells.

The anti-oxidant activity of acyl ascorbates, with acyl chain lengths of 10 to 18, was measured in an intestinal epithelial cell line. All the acyl ascorbates exhibited the activity for the oxidization induced by three different types of oxidants, at levels higher than ascorbic acid. Myristoyl ascorbate was the most effective and showed activity at 3 x 10(-12) to 3 x 10(-6) M. incubation with myristoyl ascorbate for more than 3 h was needed to sufficiently suppress the oxidization of the intestinal cell monolayers.

Relationship between structure and permeability of tryptophan derivatives across human intestinal epithelial (Caco-2) cells.

L-Trp and its derivatives were used as model compounds to clarify structural factors which influence the intestinal epithelial permeation and metabolism of amino-acid derivatives. Permeability of model compounds through Caco-2 cells was used as an in vitro absorption model for human intestinal epithelial cells. The influence of compound concentration, the effects of various transporter substrates on permeability coefficients, and pH dependency of permeability coefficients were investigated. The transcellular permeability of Trp and Trp-NH2 in the direction from the apical side to the basolateral side, in which nutrients and drugs were ordinarily absorbed, declined with increasing concentration and saturated at more than 1 and 0.4 mM, respectively. The permeability coefficients for N-terminal protected Trp derivatives and Ac-Trp-NH2 showed similar and constant values in both from the apical-to-basolateral and basolateral-to-apical directions. In addition, significant inhibition of the apical-to-basolateral permeation of Trp by Leu and Phe was observed. The permeability coefficient ratio at pH 6.3 to that at pH 7.3 was explained by the ratio of the ionic form to the neutral form of the compounds. Based upon these results and the partition coefficients in the 1-octanol/water system, possible absorption mechanism of Trp and its derivatives across Caco-2 cells was proposed.