Cholesterol (CH) is a vital mol. for mammalian life. It functions as a precursor for a variety of biol. active mols. and as a moderator of membrane mobility, and has many other essential functions. However, a high blood CH level can cause development of cardiovascular diseases. The soln. for high CH level is an intake of CH-lowering drugs such as statins. Another option for lowering excess CH is intake of phytosterols (PS) as a nutraceutical, which reduces CH absorption in mammals. PS are sterols synthesized only in plants and are structurally similar to CH but with an extra hydrophobic carbon chain at the C-24 position. PS and CH both have low soly. in oil and even lower soly. in water. To improve the efficiency of PS in lowering CH level, it is important to develop suitable vehicles that will improve their solubilization and absorption. In this entry, we examine sterol-solubilization vehicles, which include micelles, emulsions, microemulsions, and bile salt (BS) systems. The discussion focuses on the solubilization capacity (SC) of the vehicles and their effect on the extent of CH absorption/inhibition. It can be concluded that the solubilized PS in these various vehicles enables a significant decrease in CH absorption in comparison to the intake of PS in its solid form. In addn., we shall review the competitive solubilization of CH and PS in microemulsion systems to understand the competitive solubilization mechanism, which has been proposed as one of the mechanisms for PS activity as a CH-lowering agent. [on SciFinder(R)]

Double emulsions are emulsions in which an emulsion [water/oil (W/O) or oil/water] is dispersed in a continuous phase (water or oil, resp.), producing W/O/W or O/W/O. These systems have considerable potential in food systems, cosmetics, and pharmaceuticals. This entry reviews some studies and discusses the different approaches that have been introduced. The studies provide better understanding of the stabilizing mechanisms and pathways and a better control of the release patterns from double emulsions. [on SciFinder(R)]

NMR chromatog. is a promising and superior alternative to NMR spectroscopy for analyzing mixts. since it simultaneously separates the spectra of the compds. and supplies information about their structure. This implies that there is no need for extn., purifn. or synthesis of stds., that are expensive, time consuming and usually impractical. The main aim of NMR chromatog. is to increase the differences in the diffusivities of different analytes in a mixt., allowing them to be more easily and reliably identified. The selection of surfactants and other components of microemulsions for the best performance as NMR chromatog. media was studied. Attention was focused on the selection of the proper cosolvent in three types of water-dilutable microemulsions: two anionic (deuterated ionic and the previously published fluorinated ionic) and one nonionic (undeuterated Tween-based). The diffusivities of several analytes are compared. The study also examines the effect of diln. and dets. the best compns. for the NMR chromatog. performance. For the anionic microemulsions, 1-butanol was found to be the most promising cosurfactant in the deuterated system 1-butanol-d10:toluene-d8:SDS-d25 in a 6:3:1 wt.-ratio dild. by D2O. This compn., dild. with a 85 wt% D2O, formed a microemulsion that was even stable at relatively elevated temps. (70 °C) and can serve as good medium for chromatog. NMR. Another possibility that was studied consists of nonionic-based microemulsions of iso-Pr alc. (IPA) in IPA:toluene:Tween 20 that could also be easily dild. indefinitely with water. IPA was found to be a very efficient cosurfactant at resolving diffusivities of all the components. However, the lack of availability of deuterated Tween makes it impractical for use as an NMR chromatog. formulation. [on SciFinder(R)]

In microemulsions, changes in droplet size and shape and possible transformations occur under various conditions. They are difficult to characterize by most analytical tools because of their nano-sized structure and dynamic nature. Several methods are usually combined to obtain reliable information, guiding the scientist in understanding their physical behavior. We felt that there is a need for a technique that complements those in use today in order to provide more information on the microemulsion behavior, mainly as a function of dilution with water. The improvement of NMR chemical shift measurements independent of bulk magnetization effects makes it possible to study the very weak intermolecular chemical shift effects. In the present study, we used NMR high resolution magic angle spinning to measure the chemical shift very accurately, free of bulk magnetization effects. The chemical shift of microemulsion components is measured as a function of the water content in order to validate the method in an interesting and promising, U-type dilutable microemulsion, which had been previously studied by a variety of techniques. Phase transition points of the microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were successfully detected using high-accuracy chemical shift measurements. We analyzed the results and found them to be compatible with the previous studies, paving the way for high-accuracy chemical shifts to be used for the study of other microemulsion systems. We detected two transition points along the water dilution line of the concentrate (reverse micelles) corresponding to the transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets along with the changes in the droplets' sizes and shapes. The method seems to be in excellent agreement with other previously studied techniques and shows the advantage of this easy and valid technique. (C) 2014 Elsevier Inc. All rights reserved.

Molecular dynamics (MD) was employed by means of a specific simulation protocol to investigate the equilibrium structure at 25 A degrees C of the hexagonal inverted (H-II) mesophase composed from water, 1-monoolein (GMO), and tricaprylin, with or without entrapped lysozyme. Based on robust and fast MD simulations, the study provides a comprehensive analysis and visualization of the local structure of H-II mesophase containing admixtures. The most important physical insight is the possibility to observe the strong self-recovery capacity of the GMO layer, which allows the H-II mesophase tubes to reorganize and host lysozyme molecules with a size bigger than the diameter of the water channel. This is a direct message to the experimenters that the H-II mesophase has the potential to host molecules larger than the diameter of the water channel. Collective character of the interlipid interactions is outlined, which is not affected by the presence of the cargo and may be the reason for the efficient GMO reorganization. Another important result is the possible explanation of the role of triacylglycerols on the low-temperature stabilization of the H-II mesophase. The analysis shows that despite the low amount of tricaprylin, its molecules prevent the extreme inclination of the lipid tails and thus optimize the alignment capacity of the lipid tails layer. The study also reveals that the packing frustration does not depend on the temperature and the presence of admixtures. Hence, it might be numerically defined as a universal invariant parameter of a stable H-II mesophase composed of a certain lipid.

Docosahexaenoic acid (DHA) promotes synthesis of anti-inflammatory prostaglandins and relief of dry eye symptoms. However, topical ophthalmic application of DHA is difficult because of its lipophilic property. Therefore, it is important to develop aqueous-based formulation with enhanced capabilities. Novel, unique water-dilutable microemulsions (MEs) were constructed to allow loading of naturally occurring rigid long-chain triglyceride of DHA (TG-DHA). The TG-DHA serves as solubilizate and as the oil phase, therefore preparation is poor in oil. The structural transformations of MEs upon water dilution were studied by SAXS, viscosity, electrical conductivity, self-diffusion NMR, DSC, cryo-TEM, and DLS techniques. At low water content a new type of water-in-oil (W/O) structure is formed. The glycerol/water phase hydrates the headgroups of surfactants, and the oil solvates their tails, forming ``ill-defined bicontinuous domains\''\. Upon further water dilution more structured bicontinuous domains of high viscosity are formed. After additional dilution, the mesophases invert to oil-in-water (O/W) droplets of similar to 8 nm. In the structures composed of up to 25 wt% water, the TG-DHA spaces and de-entangles the surfactant tails. Once the bicontinuous structures are formed, the surfactants and TG-DHA content decrease and their interfacial layer shrinks, leading to entanglement and buildup of viscous non-Newtonian mesophase. Above 70 wt% water TG-DHA is embedded in the core of the O/W droplets, and its effect on the droplets' structure is minimal. This new dilutable ill-defined microemulsion can be a potential delivery vehicle for ophthalmic TG-DHA transport. (C) 2015 Elsevier Inc. All rights reserved.

Riboflavin phosphate (RFP) is an essential compound in the treatment of keratoconus - a degenerative, non-inflammatory disease of the cornea. Currently, the quantitative and efficient transport of riboflavin to the cornea is possible after mechanical removal of the epithelium. To avoid surgical intervention, it is therefore important to develop a method for quantitatively transporting riboflavin across the intact epithelium. In the present study, an RFP-loaded microemulsion was prepared, which could potentially function as an ocular drug delivery system crossing the eye epithelium. The specially designed water-dilutable microemulsion was based on a mixture of nonionic surfactants. Propylene glycol and glycerol acted as cosurfactant and cosolvent assisting in the solubilization of the RFP. The glycerol-rich water-free concentrate consisted of direct micelles for which glycerol served as the hydrophilic phase. In formulations with up to 40 wt% water, the hydrophilic surfactant headgroups and glycerol strongly bind water molecules (DSC and SD-NMR). Above 60 wt% water, globular, O/W nanodroplets, 14 nm in diameter, are formed (SAXS, cryo-TEM, and SD-NMR). The structure of microemulsions loaded with 0.14-4.25 wt% RFP (0.29-8.89 mmol per 100 g formulation) is not significantly influenced by the presence of the RFP. However, in the microemulsions containing 10-80 wt% water, the mobility of RFP in the microemulsion is constrained by strong interactions with the surfactants and cosurfactant, and therefore free transport of the molecule can be achieved only upon higher (\textgreater80 wt%) water dilutions. (C) 2015 Elsevier Inc. All rights reserved.

Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compds. are water-insol. and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water diln. line using ESR and pulsed-gradient spin-echo NMR along with other anal. techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water diln. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5 wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5 wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface. [on SciFinder(R)]

In this study we characterized a new and improved transport vehicle for 2,6-diisopropylphenol (propofol), a hydrophobic anesthesia drug, in the absence and presence of dendrimers being a transporting agents across cells, polypropylenimine (PPI) dendrimer generation 2 (PPI-G2) into a microemulsion (ME). Three unique systems of water-dilutable compositions capable of inverting from W/O to bicontinuous and to O/W structures upon water dilutions were studied by means of electrical conductivity, electron paramagnetic resonance (EPR), and self-diffusion nuclear magnetic resonance (SD-NMR). The microviscosity, as well as the order parameter (from EPR results) increase with the increase in the dendrimer content, while inverting the structures from W/O to bicontinuous ME. Inversion from the bicontinuous mesophase to the O/W nanodroplets caused a very minor increase in the order parameter. Self-diffusion NMR measurements provided information on the diffusivity and the interactions of the different components of the ME. It was found that propofol has no effect on the diffusivity of the components since it is embedded within the core of the ME droplets. However, the dendrimer increases the diffusivity of water. In addition, we learned that at high dendrimer content, it remains solubilized; however its location at the ME/water interface moves to the water continuous phase. The study demonstrates the ability of water dilutable MEs to act as drug carriers hosting both propofol and dendrimer. (C) 2016 Elsevier B.V. All rights reserved.

The flow behavior and viscosity of TAGs contg. oleic and stearic acids were examd. in the liq. phase as well as at temps. close to the onset of crystn. by means of a temp.-controlled rheometer. Gelling and crystn. transitions were unambiguously identified by singularities in the viscosity vs. temp. curves of the TAGs. An addnl. transition between the gelling and onset of crystn. temps., attributed to the reorganization of the gel, was obsd. in the sym. TAGs only. The effect of the cooling rate, ranging between 0.1 and 5°C/min, was investigated. The flow behavior of the studied TAGs was shown to be strongly detd. by structural parameters (symmetry, degree of unsatn.). The flow behavior was also affected significantly by the cooling rate, suggesting that to certain extents the flow behavior detd. by structural parameters could be changed by manipulating the cooling rate. The study confirmed that TAG crystn. was initiated by and depends, at least in part, on complex mol. short range order transformations occurring in the melt. The findings of the study may be valuable for evaluating systems and equipment that were involved in the storage, handling and processing of materials incorporating these TAGs. [on SciFinder(R)]

Propofol (2,6-diisopropylphenol) is a drug for both induction and maintenance of anesthesia. Pure propofol cannot be injected because of its lipophilic character, low water-solubility, and low bioavailability. Presently, propofol is formulated in an unstable emulsion, easily oxidized, and easily contaminated with bacteria. We are proposing new, propofol-loaded modified microemulsions, stable thermodynamically, and microbiologically safe; the microemulsions are fully dilutable with water. Structural characterization of the empty and the propofol-loaded systems as a function of water dilution was accomplished using advanced analytical tools such as SD-NMR, SAXS, cryo-TEM, DSC, electrical conductivity, and viscosity. Upon water dilution the propofol-loaded concentrate forms swollen reverse micelles that upon further dilution (40 wt% water) progressively transform into a bicontinuous mesophase and then invert (\textgreater65 wt% water) into O/W nanodroplets without ``losing\''\ the solubilized propofol. The drug exhibits strong interactions with the surfactant (DSC and SD-NMR). Propofol increases the size of the microemulsion nanodroplets, but does not modify the microemulsion behavior. Water, ethanol, and PG are essential structural components, but do not interact directly with propofol. (C) 2015 Published by Elsevier B.V.

The phase composition of triacylglycerols (TAG) is determined by chemical structure and is greatly affected by kinetics. Positional isomerism and unsaturation are two key structural elements that govern, for a large part, the phase behavior of TAG during crystallization. Polymorphism, thermal properties, and microstructure of dioleoyl-stearoyl isomers (OSO, SOO) were investigated at different cooling rates with XRD, DSC and PLM techniques, respectively. The physical properties of the symmetrical TAG were found to predictably vary with cooling rate; whereas, the properties of the asymmetrical TAG remained relatively constant. This was explained to be mainly due to the extra steric hindrance caused by asymmetry and the disturbances introduced at the ``terrace\''\ level via methyl-end group interactions. The findings underscore the intricate contribution of saturation and symmetry to the phase trajectories of diunsaturated TAG. The knowledge gained will help understand the behavior of more complex materials and can be used for the manipulation of fat structures at different length scales and direct the manufacture of novel food systems and other relevant materials.

In this paper the cosolubilization of 2nd, 3rd, and 4th generations of polypropyleneimine (PPI: PPI-G2, -G3, and -G4) dendrimers with sodium diclofenac (Na-DFC) into reverse gyroid cubic (QG) liq. crystals is reported. Structural properties and interactions of PPI dendrimers with and without the drug were studied using small-angle X-ray scattering, attenuated total reflected Fourier transform IR (ATR-FTIR) spectroscopy, and differential scanning calorimetry (DSC) measurements. Incorporation of PPI-G2 (without Na-DFC) into QG mesophase led to a decrease of 78 \AA in the lattice parameter. Solubilization of higher PPI generations, G3 and G4, led to increases in the lattice parameter to 57 \AA and 64 \AA, resp. At 25 wt%, each of the dendrimers caused a phase transition QG → reverse hexagonal (HII). According to ATR-FTIR and DSC, the large lattice parameter values of G3 and G4 (relative to G2) embedment were assigned to their interactions with the carboxyl groups of GMO at the interface in comparison to the strong interaction of PPI-G2 with the water. Cosolubilization of Na-DFC with PPI-G2 revealed enlargement of the lattice parameter (of the new HII mesophase), while in the case of G3 and G4 systems no significant influence was seen with Na-DFC. The release of Na-DFC from QG and HII systems was followed by UV-vis spectroscopy and revealed generation-dependence on drug release. As dendrimer generation increased, the cumulative drug release decreased. [on SciFinder(R)]

The effect of second, third, and fifth generations of poly(propylene imine) glycodendrimers-open maltose shell (PPI-Mal) on reverse hexagonal (HII) mesophase and on the release of sodium diclofenac (Na-DFC) drug was investigated. The HII mesophase comprised glycerol monooleate (GMO)/tricaprylin (TAG) in a wt. ratio of 90/10 and 20 wt. % water (+0.5 wt. % PPI-Mal of each generation) without or with 0.25 wt. % (Na-DFC). The microstructural characteristics of these systems were detd. by small-angle X-ray scattering; attenuated total reflectance Fourier transform IR was used to characterize the mol. level interactions and the location of the PPI-Mal. Third-and fifth-generation PPI-Mal, because of their maltose groups, interact mainly with the bulk water within the cylinders of the HII and strongly bind the water mols., as manifested by the decrease in the lattice parameter and dehydration of the lipid headgroups. Co-solubilization of Na-DFC with the third and fifth generations caused competition of the two host compds. for water binding and induced relocation of the drug from the bulk water to the GMO-water interface. In vitro release of Na-DFC from the HII showed that the release process was faster in the systems with third- and fifth-generation PPI-Mal compared with the control and second-generation systems. [on SciFinder(R)]

Two non-steroidal anti-inflammatory drugs (NSAIDs), sodium diclofenac (Na-DFC) and celecoxib (CLXB) were solubilized within cubic and lamellar mesophases as carriers for transdermal drug delivery. SD-NMR, SAXS, ATR-FTIR, and EPR measurements were performed to examine the systems' characteristics and the interactions between the drugs and their hosting mesophases. The amphiphilic drug Na-DFC was found to incorporate at the interfaces of the cubic and lamellar mesophases and thus to act as a cosurfactant and a "structure stabilizer". It increased the order degree and the interactions between the GMO mols. and led the systems toward denser packing. CLXB exhibits an opposite effect on the mesophases. Its solubilization within both systems is accompanied with significant channel swelling and decrease in the order degree. The hydrophobic, rigid and bulky CLXB behaves as a "structure breaker", incorporated between the GMO tails, disturbing the mesophase packing and enhancing the repulsion at the tails region, limiting their close binding. Release expts. from Franz cells revealed that Na-DFC release is dependent on the quantity of water within the hosting mesophase as the water-rich formulation exhibits 1.5-fold enhancement in the release of the drug, compared to the lamellar phase. In contrast, CLXB release was not influenced by the water quantity, hinting that the release mechanisms of the drugs are different while Na-DFC diffuses from the water channels to the external phase, CLXB diffusion occurs through the continuous lipophilic region. The difference in the solubilization sites and interactions of each drug with the mesophases affect their release profiles and det. the preferred formulations for each drug's delivery vehicle. [on SciFinder(R)]