Main factors governing the transfer of carotenoids from emulsion lipid droplets to micelles.
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Carotenoids might lower the incidence of several diseases, yet the mechanisms governing their intestinal absorption are still poorly understood. The aim was to identify and study the main factors governing the transfer of carotenoids from emulsion lipid droplets to mixed micelles, presumed to be a key step in carotenoid absorption. An in vitro model was devised to measure the transfer, and a factorial design was applied to identify the main factors affecting the transfer. Experiments were then conducted to assess the effect of physiological variations of the main factors on the transfer efficiency. Finally, different carotenoids were simultaneously incorporated in emulsion lipid droplets to determine whether they interacted during the transfer. The factorial design gave three factors that significantly affected the transfer: type of carotenoid, pH, and bile lipid concentration. The transfer was (i) inversely related to carotenoid hydrophobicity, (ii) maximum between pH 6 and 7, (iii) maximum from 2 mmol/l bile salts, (iv) impaired by other carotenoids in the case of carotenes, but not in the case of xanthophylls. The transfer mainly depends on carotenoid hydrophobicity, pH, and bile lipid concentration. Physiological variations in pH and bile lipid concentration markedly affect the transfer. Both carotenes and xanthophylls can impair the transfer of carotenes, whereas they have apparently no effect on the transfer of xanthophylls. (+info)
A novel in vitro release method for submicron sized dispersed systems.
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Sink conditions are often violated when using conventional release methods for dispersed systems. A novel reverse dialysis bag method was designed to overcome this problem. Model drug transport rates from submicron emulsions obtained using the conventional diffusion cell method and this novel method were compared. In the side-by-side diffusion cell method, emulsions were placed in the donor chamber and surfactant/buffer solutions in the receiver chamber. In the novel dialysis bag method, emulsions were diluted infinitely in the donor phase and surfactant/buffer solutions were placed in the receiver phase (dialysis bags). Slow release rates and linear release profiles were obtained using the side-by-side diffusion cell method apparently due to limited model drug solubility in the donor chamber resulting in violation of sink conditions. Biphasic release profiles were obtained using the dialysis bag method apparently due to an initial rapid release of free and micellar solubilized model drug from the donor to the receiver chambers followed by slow release from the oil droplets. Using both release methods, an initial increase and latter decrease in release rates were observed with increase in surfactant concentration. The initial increase was considered to be due to a decrease in the model drug oil-in-water partition coefficients and the subsequent decrease in release rates was due to micellar shape change (spheres to rods) causing a decrease in diffusion rates. Sink conditions were violated using the side-by-side diffusion cell method but were maintained in the dialysis bag method since emulsions were diluted infinitely in the donor phase. (+info)
Light scattering investigations on dilute nonionic oil-in-water microemulsions.
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Dilute 3-component nonionic oil-in-water microemulsions formulated with either a polyoxyethylene surfactant (C18:1E10 or C12E10) or the alkylamine-N-oxide surfactant, DDAO (C12AO), and containing either a triglyceride or an ethyl ester oil have been examined using dynamic and static light-scattering techniques. Analysis of the results showed distinct differences in the tested oil's mode of incorporation into the microemulsion droplets, with both the molecular volume of the oil and the hydrophobic chain length of the surfactant being important. For example, microemulsions formulated by C18:1E10 and containing one of the larger molecular volume oils (that is, either a triglyceride, Miglyol 812, or soybean oil) or the ethyl ester of fatty acid oil, ethyl oleate, exhibited first a decrease and then an increase in hydrodynamic size and surfactant aggregation number, suggesting that the asymmetric C18:1E10 micelles became spherical upon the addition of a small amount of oil and grew thereafter because of further oil being incorporated into the core of the spherical microemulsion droplet. A similar conclusion of sphericity could not be drawn for microemulsions stabilized by C18:1E10 and containing one of the oils smaller in molecular volume (namely tributyrin, ethyl butyrate, or ethyl caprylate) where neither the aggregation number nor the hydrodynamic radius changed much upon the addition of oil. This result suggested that these oils were preferentially located in the interfacial surfactant monolayer, behaving in much the same way as a cosurfactant. A different trend of results, however, was seen for microemulsions prepared using C12E10 and C12AO, most likely because these surfactants produced approximately spherical micelles. In this case, the microemulsions containing the oils larger in molecular volume tended to exhibit an increase in surfactant aggregation number and hydrodynamic size, suggesting the growth of spherical micelles, while the smaller oils (in particular ethyl butyrate) caused a significant decrease in surfactant aggregation number incompatible with their being incorporated into the centre of the droplet, suggesting that the oils were being located in the interfacial surfactant monolayer. These results suggest that the various oils are incorporated into the microemulsions in very different ways. (+info)
Particle size analysis of concentrated phospholipid microemulsions I. Total intensity light scattering.
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Water-in-oil phospholipid microemulsions prepared from a constant total surfactant/cosurfactant concentration of 25 wt% at four different lecithin/alcohol weight ratios (Km of 1:1, 1.5:1, 1.77: 1, and 1.94:1) and containing water concentrations (or volume fractions) ranging from 2.0 to 26 wt% (or 0.04 to 0.26) have been examined at 298 K using total intensity light scattering. The data obtained were analysed using the hard-sphere model of Percus-Yevick, modified to account for the partitioning of the alcohol between the various phases. The light-scattering results showed that, regardless of the Km or the alcohol used, a minimum water concentration of at least 9 wt% was required for the formation of a microemulsion; although this value was reasonably constant for each of the alcohols investigated, there was a tendency for a slightly higher concentration of water to be required for microemulsion formation at higher Km values. Simple calculations suggested that a microemulsion was formed only when sufficient water was present to satisfy the hydration of both the phospholipid head groups and the hydroxyl groups of the cosurfactant associated with the droplet. At water concentrations lower than this minimum value, a cosolvent system was observed. In all systems above this minimum concentration, as the concentration of water increased, the size of the microemulsion droplets also increased. Surprisingly, however, there was little difference in the size of the microemulsion droplets obtained with the different alcohols, regardless of the Km, although for a particular alcohol there was some indication that the higher Km systems produced the slightly smaller droplets for an equivalent water concentration. There was also a suggestion that the more hydrophobic alcohols produced slightly smaller droplets than the more polar alcohols at the same Km. (+info)
Particle size analysis of concentrated phospholipid microemulsions II. Photon correlation spectroscopy.
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The solvated droplet size of concentrated water-in-oil (w/o) microemulsions prepared from egg and soy lecithin/water/isopropyl myristate and containing short-chain alcohol cosurfactants has been determined using photon correlation spectroscopy (PCS). The effect of increasing the water volume fraction (from 0.04 to 0.26) on the solvated size of the w/o droplets at 298 K has been investigated at 4 different surfactant/cosurfactant weight ratios (Km of 1:1, 1.5:1, 1.77:1, and 1.94:1); in all cases the total surfactant/cosurfactant concentration was kept constant at 25% w/w. In the case of the microemulsions prepared from egg lecthin, the diffusion coefficients obtained from PCS measurements were corrected for interparticulate interactions using a hard-sphere model that necessitated estimation of the droplet volume fractions, which in the present study were obtained from earlier total intensity light-scattering (TILS) studies performed on the same systems. Once corrected for hard-sphere interactions, the diffusion coefficients were converted to solvated radii using the Stokes-Einstein equation assuming spherical microemulsion droplets. For both egg and soy lecithin systems, no microemulsion droplets were detected at water concentrations less than 9 wt% regardless of the alcohol and Km used, suggesting that at low concentrations of added water, cosolvent systems were formed. At higher water concentrations, however, microemulsion droplets were observed. The changes in droplet size followed the expected trend in that for a fixed Km the size of the microemulsion droplets increased with increasing volume fraction of water. At constant water concentration, droplet size decreased slightly upon increasing Km. Interestingly, only small differences in size were seen upon changing the type of alcohol used. The application of the hard-sphere model to account for interparticulate interactions for the egg lecithin systems indicated that the uncorrected diffusion coefficients underestimated particle size by a factor of slightly less than 2. Reassuringly, the corrected droplet sizes agreed very well with those obtained from our earlier TILS study. (+info)
Effect of nonionic surfactant on transport of surface-active and non-surface-active model drugs and emulsion stability in triphasic systems.
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The effect of surfactant concentration on transport kinetics in emulsions using surface-active (phenobarbital, barbital) and non- surface-active (phenylazoaniline, benzocaine) model drugs is determined. Mineral oil was chosen as the oil phase and the nonionic surfactant polyoxyethylene-10-oleyl-ether (Brij 97) was chosen as the emulsifier. Model drug transport in the triphasic systems was investigated using side-by-side diffusion cells mounted with hydrophilic dialysis membranes (molecular weight cutoffs 1 kd and 50 kd) and a novel bulk equilibrium reverse dialysis bag technique. Emulsion stability was determined by droplet size analysis as a function of time, temperature, and the presence of model drugs, using photon correlation spectroscopy. Mineral oil/water (O/W) partition coefficients and aqueous solubilities were determined in the presence of surfactant. The transport rates of model drugs in emulsions increased with an increase in Brij 97 micellar concentrations up to 1.0% wt/vol and then decreased at higher surfactant concentrations. The transport profiles of the model drugs appeared to be governed by model drug O/W partition coefficient values and by micellar shape changes at higher surfactant concentrations. Total transport rates of phenobarbital and barbital were faster than those of phenylazoaniline and benzocaine. Excess surfactant affected the transport rates of the model drugs in the emulsions depending on drug surface activity and lipophilicity. (+info)
Mathematical modeling of surface-active and non-surface-active drug transport in emulsion systems.
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Mathematical models were developed for the prediction of surface-active and non- surface-active drug transport in triphasic (oil, water, and micellar) emulsion systems as a function of micellar concentration. These models were evaluated by comparing experimental and simulated data. Fick's first law of diffusion with association of the surface-active or complexation nature of the drug with the surfactant was used to derive a transport model for surface-active drugs. This transport model assumes that the oil/water (O/W) partitioning process was fast compared with membrane transport and therefore drug transport was limited by the membrane. Consecutive rate equations were used to model transport of non-surface-active drugs in emulsion systems assuming that the O/W interface acts as a barrier to drug transport. Phenobarbital (PB) and barbital (B) were selected as surface-active model drugs. Phenylazoaniline (PAA) and benzocaine (BZ) were selected as non- surface-active model drugs. Transport studies at pH 7.0 were conducted using side-by-side diffusion cells and bulk equilibrium reverse dialysis bag techniques. According to the surface-active drug model, an increase in micellar concentration is expected to decrease drug-transport rates. Using the Microsoft EXCEL program, the non-surface-active drug model was fitted to the experimental data for the cumulative amount of the model drug that disappeared from the donor chamber. The oil/continuous phase partitioning rates (k1) and the membrane transport rates (k2) were estimated. The predicted data were consistent with the experimental data for both the surface-active and non- surface-active models. (+info)
Lipase-catalysed hydrolysis of short-chain substrates in solution and in emulsion: a kinetic study.
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We have studied the enzymatic hydrolysis of solutions and emulsions of vinyl propionate, vinyl butyrate and tripropionin by lipases of various origin and specificity. Kinetic studies of the hydrolysis of short-chain substrates by microbial triacylglycerol lipases from Rhizopus oryzae, Mucor miehei, Candida rugosa, Candida antarctica A and by (phospho)lipase from guinea-pig pancreas show that these lipolytic enzymes follow the Michaelis-Menten model. Surprisingly, the activity against solutions of tripropionin and vinyl esters ranges from 70% to 90% of that determined against emulsions. In contrast, a non-hyperbolic (sigmoidal) dependence of enzyme activity on ester concentration is found with human pancreatic lipase, triacylglycerol lipase from Humicola lanuginosa (Thermomyces lanuginosa) and partial acylglycerol lipase from Penicillium camembertii and the same substrates. In all cases, no abrupt jump in activity (interfacial activation) is observed at substrate concentration corresponding to the solubility limit of the esters. Maximal lipolytic activity is always obtained in the presence of emulsified ester. Despite progress in the understanding of structure-function of lipases, interpretation of the mode of action of lipases active against solutions of short-chain substrates remains difficult. Actually, it is not known whether these enzymes, which possess a lid structure, are in open or/and closed conformation in the bulk phase and whether the opening of the lid that gives access to the catalytic triad is triggered by interaction of the enzyme molecule with monomeric substrates or/and multimolecular aggregates (micelles) both present in the bulk phase. From the comparison of the behaviour of lipases used in this study which, in some cases, follow the Michaelis-Menten model and, in others, deviate from classical kinetics, it appears that the activity of classical lipases against soluble short-chain vinyl esters and tripropionin depends not only on specific interaction with single substrate molecules at the catalytic site of the enzyme but also on physico-chemical parameters related to the state of association of the substrate dispersed in the aqueous phase. It is assumed that the interaction of lipase with soluble multimolecular aggregates of tripropionin or short-chain vinyl esters or the formation of enzyme-substrate mixed micelles with ester bound to lipase, might represent a crucial step that triggers the structural transition to the open enzyme conformation by displacement of the lid. (+info)