In this paper the authors examd. feasible correlations between the structure of different lyotropic mesophases and transdermal administration of three diclofenac derivs. with varying degrees of kosmotropic or chaotropic properties, solubilized within the mesophases. It was found that the most chaotropic deriv. of diclofenac di-Et amine (DEA-DFC) interacted with the polar heads of glycerol monooleate (GMO), thus expanding the water-lipid interface of the lamellar and cubic mesophases. This effect was detected by an increase in the lattice parameter of both mesophases, enhanced elastic properties, and increased solid-like response of the systems in the presence of DEA. Potassium diclofenac (K-DFC), a less chaotropic salt, had less pronounced effect on the structural features of the mesophases. Kosmotropic Na+ salt (Na-DFC) had only minor influence on both lamellar and cubic structures. The locus of solubilization of the mols. with the host mesophases was correlated with their delivery. It was suggested that transdermal delivery of kosmotropic Na-DFC was accelerated by the aq. phase and less constrained by the interaction with monoglyceride. The chaotropic cations (K+ and DEA+), presumably entrapped in the water-lipid interface, interacted with monoglyceride headgroups, which is likely to be the key cause for their sustained administration. [on SciFinder(R)]

The use of phospholipids (PL) as surfactants in micellar systems and microemulsions offers many advantages as drug delivery vehicles. PL are commonly used in combination with other non-food surfactants with cosolvents and cosurfactants to form a cascade of delivery structures. The authors incorporated phosphatidylcholine (PC) in a unique U-type water-dilutable phase diagrams exhibiting large isotropic regions of nanostructures. The nanometric liq. structures were prepd. from food-grade emulsifiers. The authors formed water-free concs. with PC that are fully dild. with water to form a variety of unusually structured nanodroplets. Due to the uniqueness of their compn., the designed concs. derived from the nature of the oil phase, type of surfactants, and cosurfactants were characterized and found to be direct micelles (rather than inverse micelles), with the surfactant headgroups convexed toward the hydrophilic phase away from the micelle's core, even in the absence of water. The concs. tend to self-assemble upon adding water to form O/W microemulsions even with small amts. of water (water-poor compns. of 0-20% water). Upon further diln. with water the swollen micelles retain the oil as the inner phase. Multi-component compns. with two types of hydrophilic surfactants were investigated. The most significant enhancement in the total isotropic region was obtained by decreasing the triacetin and PC content in the system. The authors explored, by varying the nature of the headgroups and the nature and length of the lipidic (lipophilic) tails of the PL, the diln. capabilities of each of the systems. [on SciFinder(R)]

A review. Coenzyme Q10, present in all cells and membranes, is essential for electron transport in the mitochondrial respiratory chain, antioxidant defense, and other functions of great importance for cellular metab. The essential advantages of CoQ10, combined with its poor and slow absorption, generated the need to develop new technologies for delivery. Therefore, much effort has been expended to design delivery vehicles that can improve its aq. soly. and overall bioavailability for oral and topical administration. This chapter summarizes the findings available today concerning CoQ10 chem. characteristics, human functionalities, its impact on human diseases, and new techniques developed to enhance its delivery. [on SciFinder(R)]

A review. Liq. crystals are widely utilized as model systems to mimic biol. processes where the phase behavior of lipids plays a mediating role. In various foods and pharmaceutical and biotech. applications, the liq. cryst. phases formed by surfactants in an aq. medium represent useful host systems for drugs, amino acids, peptides, proteins and vitamins. Various biol. active food additives are sol. in neither aq. nor oil phase and require environmental protection against hydrolysis or oxidn. Lyotropic liq. crystals meet these requirements mainly due to their high solubilization capacities for hydrophilic, lipophilic and amphiphilic guest mols. Moreover, recent studies demonstrated controlled and/or sustained release of solubilized mols. from different liq. cryst. matrixes. This paper surveys the solubilization of hydrophilic, lipophilic and amphiphilic guest mols. for food applications and illustrates the corresponding structural transformations. Recent developments in liq. crystal characterization methods are discussed. [on SciFinder(R)]

We investigated the effect of ascorbic acid (AA) cosolubilized with vitamin E (VE) on reverse hexagonal (HII) mesophase. The HII phase comprises monoolein (GMO)/D-$\alpha$-tocopherol (VE) in a ratio of 90/10 by wt. and 12.5 wt% water. The macrostructural characteristics of this system were detd. by polarized light microscopy and small-angle X-ray scattering measurements. We used differential scanning calorimetry and attenuated total reflectance Fourier transform IR to characterize the microstructure, the vibration of the functional groups, and the location of the AA guest mol. AA was incorporated to the system in two steps: 1-4 wt% AA and 5-6 wt% AA. We compared this system to one contg. tricaprylin as the oil phase, as previously reported. These measurements revealed that AA is localized first in the water rich-core and in the interface, and acts as a chaotropic mol. that decreases the water m.p. When a larger quantity of AA (5-6 wt%) is added, the system is satd., and the AA is located in the inner cylinder and manifested by more moderate distortion. The addn. of AA also causes alteration in the behavior of the GMO hydrocarbon chains and makes them more flexible. Further addn. of AA caused the GMO hydrocarbon chain to be more solvated by the VE hydrocarbon chain and enabled addnl. migration of VE; hence a decrease in the hydrophobic melting temp. occurred (similar to tricaprylin). Increasing the amt. of AA weakened the bonding between the GMO and water and created new bonds between AA and GMO and AA with water. [on SciFinder(R)]

Hydrophobic bioactive guest mols. were solubilized in the discontinuous cubic mesophase (QL) of monoolein. Their effects on the mesophase structure and thermal behavior, and on the formation of soft nanoparticles upon dispersion of the bulk mesophase were studied. Four additives were analyzed. They were classified into two types based on their presumed location within the lipid bilayer and their influence on the phase behavior and structure. Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), polarized light microscopy, cryogenic-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS) were used for the anal. We found that carbamazepine and cholesterol (type I mols.) likely localize in the hydrophobic domains, but close to the hydrophobic-hydrophilic region. They induce strong perturbation to the mesophase packing by influencing both the order of the lipid acyl chains and interactions between lipid headgroups. This results in significant redn. of the phase transition enthalpy, and phase sepn. into lamellar and cubic mesophases above the max. loading capacity. The inclusion of type I mols. in the mesophase also prevents the formation of soft nanoparticles with long-range internal order upon dispersion. In their presence, only vesicles or sponge-like nanoparticles form. Phytosterols and coenzyme Q10 (type II mols.) present only moderate effects. These mols. reside in the hydrophobic domains, where they cannot alter the lipid curvature or transform the QL mesophase into another phase. Therefore, above max. loading, excess solubilizate ppts. in crystal forms. Moreover, when type II-loaded QL is dispersed, nanoparticles with long-range order and cubic symmetry (i.e., cubosomes) do form. A model for the growth of the ordered nanoparticles was developed from a series of intermediate structures identified by cryo-TEM. It proposes the development of the internal structure by fusion events between bilayer segments. [on SciFinder(R)]

A review on cubosomes, nanosoft particles that are formed when the liq. cryst. cubic phases are dispersed in aq. phase contg. a stabilizer (usually amphiphilic polymer), and their potential use as drug delivery vehicles. In the dispersed soft matter particles, the nanostructure of the original cubic inner structure remains intact despite the dispersion process. The three-dimensional symmetry of the cubic phases, combined with their large interfacial area and balanced content of hydrophobic and hydrophiic domains, make them very promising universal drug carriers, with numerous advantages over most other systems used at present. These exceptional phys. and chem. properties stimulated the study of the liq. crystal dispersions. Thus, one can take advantage of the complex phases for controlled delivery, while simultaneously having the benefit of the low viscosity of a system of soft nanoparticles dispersed in a continuous aq. phase. [on SciFinder(R)]

A dielectric study of reverse hexagonal mesophases (H(II)) is presented. Conducted in the frequency range 0.01-1 MHz and temperature range 293 \textless T \textless 319 K, the study reveals complex molecular behavior in and around the interfaces of the mesoscopic structures of the gel. There exist three clearly defined dielectric relaxations related to separate moieties in the interface, as well as a temperature-activated dc conductivity. A critical temperature, T(0) = 307 K, is noted in the results and related to the dehydration of the glycerol monooleate (GMO) head groups. Effectively, this represents a break-down of the interfacial layer of water. The consequences of this act are clearly visible in the change in behavior of the fitting parameters for all processes. A physical picture emerges whereby at T(0) = 307 K, the ``loosening\''\ of the GMO heads accentuates the dangling motion of the phosphatidylcholine (PC) tails, evidenced by counterion motion along the PC head. Furthermore, it precipitates the percolation of the large TAG molecules that are intercalated in the GMO and PC tails.

Fractionation of Valencia orange pulp prepns. resulted in PME active fractions contg. putative PMEs of 13, 27, and 36 kDa. NMR anal. indicated that pectin de-esterification by PMEs in these fractions resulted in block wise de-esterification of the substrate. Within the narrow frequency range of 0.57 to 0.76 for the dyad or 0.22-0.55 for the triad, little effect on G' value near 560 Pa is obsd. The relative contribution of total charge or distribution of charge cannot be clearly elucidated as the contribution of either depends on achieving a crit. limit of de-esterification. The position and shape of this crit. limit is influenced by the compn. of the dyads and triads of carboxylic acid groups. Applications of charge modified pectins include the ability to interact with proteins, stabilize emulsions for entrapment of addenda and for drug release. Under low pH, cationic milk proteins interact readily with pectins, esp. charge modified pectins. At pH 3.8, non fat dry milk, caseinates, $\alpha$S1,2, $\beta$- but not $ąppa$-casein pptd., esp. with modified pectin. Modified pectin apparently increased the soly. of sodium caseinate, suggesting a competition between protein-protein and protein-pectin interactions. Further, charge modified pectins reduced the surface tension and interfacial activity of dispersions and reduced the droplet size of emulsions. Finally, modified pectins showed superior entrapment and less release of indomethacin compared to com. low methoxyl pectins. [on SciFinder(R)]

The effect of the solubilized model drug, carbamazepine, on the internal structure of fully dilutable nonionic microemulsions was examd. for the first time using ESR. Systems contg. different surfactant to oil ratios, at two different pH values (4.6 and 8.5), with continuous diln. implementing structural transformations (micellar soln.-W/O-bicontinuous-O/W) were investigated. The internal order, micropolarity, and microviscosity were scrutinized utilizing pH-dependent amphiphilic probe 5-doxylstearic acid (5-DSA). In the basic environment, the probe explored the vicinity of the surfactant head region; the deeper hydrophobic region of the surfactant tails was investigated in the acidic milieu. The study demonstrated that the EPR technique enables efficient monitoring of structural changes and examn. of drug influence on structure in surfactant-poor systems. Lower order and microviscosity values were obtained in surfactant-poor systems in comparison to surfactant-rich systems. The drug functioned as a spacer of the surfactant mols. or as a cosurfactant depending on the formed microemulsion structure and the surfactant to oil ratio. The structural changes, pH variation, and presence of the drug did not alter the polarity parameter, indicating that the probe most likely does not sense a water environment in any of the examd. systems. Under the basic conditions, higher microviscosity and order values were obtained in comparison to those at low pH, suggesting a higher order packing of the surfactant chains near the surfactant heads. The structural changes initiated in the vicinity of the surfactant heads, therefore, are more apparent in the basic environment. The ability to control and monitor the intramicellar interactions within drug carrier systems may be of significant interest for understanding the kinetics of drug release. [on SciFinder(R)]

Ordered bicontinuous microstructures formed in a fully water-dilutable, pseudoternary unique nonionic microemulsion were obtained and characterized. The conc. contained a mixt. of triacetin/D-$\alpha$-tocopherol acetate/ethanol/Tween 60. Upon diln., the conc. was transformed from a reversed micellar system to oil-in-water microemulsion droplets. The transformation occurred through an intermediate phase of ordered bicontinuous structures. The factors that governed the construction of this unique phase, and its phys. and structural properties, were characterized in detail. The techniques used included small angle X-ray scattering (SAXS), self-diffusion and quantum filtered NMR, differential scanning calorimetry, rheol. measurements, elec. cond., and dynamic light scattering. This mesophase displays microemulsion properties along with some characteristics of lyotropic liq. crystals (but is not a mixt. of the two). Similar to microemulsions, the structures were transparent and spontaneously formed and exhibited thermodn. stability. Yet, unlike microemulsions, they showed short-range order at room temp. Addnl., the microstructures exhibited non-Newtonian flow behavior, characteristic of lamellar structures. The bicontinuous ordered microemulsions were obtained upon heating (to 25 °C) from the lamellar phase existing at low temps. (5 °C). The main feature governing the bicontinuous mesophase formation was the amphiphilic nature of oil blends composed of D-$\alpha$-tocopherol acetate and triacetin. The oils functioned as cosurfactants, altering the packing parameter of the surfactant and leading to the construction of bicontinuous structures with short-range order. These unique structures might have drug or nutraceutical delivery advantages. [on SciFinder(R)]

In this paper we report on the solubilization of desmopressin, as a model for peptide drugs, into reverse hexagonal (HII) liq. crystals. Concn.- and temp.-induced interactions of desmopressin, as well as the conformation of the peptide, were studied using small-angle X-ray scattering, ATR-FTIR spectroscopy, SD-NMR, and rheol. measurements. A considerable increase (up to 6 \AA) in the lattice parameter of the mesophases was obtained upon incorporation of the peptide. According to the ATR-FTIR anal., the chaotropic effect of peptide embedment was assigned to its interactions with hydroxyls of monoglyceride in the outer interface region. These interactions had only a minor influence on the conformation of the peptide; weakening or opening the $\gamma$-turns resulted in partial binding of the peptides free carbonyls to monoolein. Temp.-dependent SAXS measurements displayed a chaotropic destabilizing effect of desmopressin on the structure, shifting toward the lower temp. HII-L2 structural transition. Temp. increase resulted in an increase of the domain size in the presence of the peptide, in contrast to the trend obsd. in the empty mesophase. SD-NMR anal. enabled distinguishing between two factors impeding the diffusion of the peptide: the restriction of motion due to the geometrical constrain of diffusion within the water tubes, and the interactions of the guest mol. with monoglyceride. The onset of the crit. behavior at 45 °C was found to be significant, indicating considerable weakening of the monoglyceride and desmopressin interactions and the destabilizing effect of the peptide on the mesophase above this temp. Similar temp.-dependent behavior was revealed by rheol. measurements displaying the same onset of the crit. behavior. It was demonstrated by Franz diffusion cell measurements that hexagonal mesophases can potentially be used as delivery vehicles for sustained delivery of desmopressin. [on SciFinder(R)]

Double emulsions based on naturally occurring stabilizers for food applications were studied. Two charged biopolymers, whey protein isolate (WPI) and enzymic modified pectins, interacted in aq. soln. to form a charge-charge complex that was utilized as a hydrophilic polymeric steric stabilizer improving the double emulsion stability. The main factors that influence the interaction between protein and pectin were investigated in relation to double emulsion stability: creaming, coalescence, and water transport between aq. phases. The pH detd. the size of the complex formed. Thus at pH 6, where a sol. complex was obtained between some mol. pos. charged patches on the protein and neg. charged fractions of the hydrocolloids, the double emulsion was the most stable. With the smallest droplet size (∼15 $μ$m), the lowest creaming, highest yield, and minimized water transport were obtained. The best concn. and ratio to form the sol. complex are 4% WPI and 0.5% pectin (for 30% of the W/O inner phase). The influence of the charge distribution (degree of order of the carboxylic groups) of the pectin on the assocd. complex was also investigated, and it was found that the more "ordered" pectin (U63) formed the most stable double emulsion against water transport. [on SciFinder(R)]