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)]

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)]

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)]

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.

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)]

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)]

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)]

The conditions necessary to form an assocd. complex between whey protein isolate (WPI) and enzymically modified pectin in water, at pH values above the isoelec. point of the protein, have been documented. The existence of the complex is not easily verified and its characterization in soln. is even more complicated, since the structure is an intermediate entity between the non-interacting, incompatible aq. sol. mixt. of the biopolymers, and a strongly interacting coacervated pptg. complex. Evidence for the formation of this assocd. complex is provided from confocal laser scanning microscope images and rheol. behavior of the aq. mixts. The assocd. complex is characterized by small fluorescent "patches" interpreted as small aggregates. The viscosity of this soln. is greater than that of its individual biopolymer constituents, indicating a synergy of attractive interactions that occurs in the soln. While individually, the pectin and the WPI solns. at the studied range of concns. exhibit moderately non-Newtonian behavior, at sp. wt. ratios, mixts. of the two behave either as highly entangled polymeric structures or as weak gels. The values of the storage modulus G' are equal to or greater than those of the loss modulus G''. We conclude that the assocd. complexes are formed at pH 6, and at 4 wt% WPI with a pectin concn. ranging from 0.1 to 0.75 wt%. The influence of the charge distribution (degree of order of the carboxylic groups) of pectin on the assocd. complex was also investigated, and it was found that the more "ordered" pectin (U63) favors the formation of the assocd. sol. complex. [on SciFinder(R)]

This paper describes the formation and characterization of liq. cryst. dispersions based on the hexagonal phase of GMO/tricaprylin/water. As a stabilizer of the soft particles dispersed in the aq. phase, a non-ionic, non-polymeric surfactant-ethoxylated phytosterol with 30 oxyethylene units (PhEO) was utilized. In contrast to Pluronic copolymers, normally utilized in the stabilization of liq. cryst. dispersions with ordered inner structure, use of such non-polymeric surfactant is not a common practice in this field. The authors revealed how properties of these particles, such as internal structure, size, and stability, can be rationally modified by the concn. of the stabilizing agent and processing conditions. The phys. stability of the hexosomes was further examd. by the LUMiFuge technique. Structural effect of PhEO solubilization on the properties of the bulk HII mesophase system showed that phase behavior was greatly influenced following phase transitions: HII → HII + cubic → cubic + L$\alpha$ → L$\alpha$. The decrease of hydrogen bonding of the hydroxyl and carbonyl groups of monoolein with water and simultaneous hydration of EO groups of PhEO appeared to be important for the obsd. behavior. The use of PhEO as a dispersant resulted in a soft matter multi-phase water dispersion with bimodal distribution of the particle population. Effective stabilization of hexosomes was obtained in an extremely narrow concn. range of PhEO (0.1-0.2%), coexisting with small vesicles and disordered particles. At higher PhEO content, particles had disordered inner structure, and unilamellar and multilamellar vesicles, at the expense of hexosomes in consequence of incorporation of the dispersant into the hexosome structure. PhEO was found to induce lamellar phase formation, introducing disorder into the hexagonal LLC and reducing their domain size. Finally, hexosomes were evaluated as delivery vehicles for the therapeutic peptide desmopressin. Sustained release of this drug was obsd. during the first 10 h; however, permeation drastically increased in the 10-24 h range. [on SciFinder(R)]