The physical and the interfacial properties of pectins de-esterified by a specific block-wise enzymatic procedure were investigated. Two major types of block-wise de-esterified pectins with different internal distribution of carboxylic acid on the pectin chains were explored. Type C and type U pectins with the same degree of methylesterification are different and a more block-wise intramolecular distribution in comparison to commercial native apple pectin. The most ordered pectin (U63 pectin, 63% methyl-esterified pectin) has the highest electrophoretic mobility (zeta-potential). It reveals more pronounced intermolecular interactions since it exhibited, at low pH, the lowest circular dichroism intensity at shorter wavelength. U63 pectin (at acidic pH, without calcium addition) has a higher viscosity and formed a stronger gel compared to the less ordered C63 pectin and/or native apple pectin. X-ray patterns show that powdered U63 pectin is more crystalline than C63 pectin, while apple pectin is mostly amorphous. The modified pectin also, most effectively, reduced the surface tension (55 mN/m) and the interfacial tension (5.6 mN/m), probably due to the preferred surface orientation of the carboxylic groups at the water/air or water/oil interfaces. It was demonstrated that the internal charge distribution within the backbone of the pectin is an effective factor in its crystalline organization and its solution properties. It is, therefore, expected that the U63 pectin will exhibit better emulsification capabilities and will form stronger complexes with proteins. (C) 2008 Elsevier Ltd. All rights reserved.

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)]

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)]

One of the theories for the redn. of cholesterol (CH) in the blood stream by the consumption of phytosterols (PS) states that these two types of sterols compete for solubilization within the dietary mixed micelles (DMM). In this study, a fully dilutable nonionic microemulsion system was used as a model to explain a possible competitive solubilization mechanism of CH and PS mols. using an EPR technique that reveals relevant intra-micellar properties. The effect of the solubilized sterols on the structural changes occurring in the vicinity of the surfactant head groups or closer to the oil phase was examd. by controlling the pH of the environment, which influences the probe locus between the surfactant mols. The results indicate that the structure transformations in the surfactant layer closer to the vicinity of the head groups region are more pronounced than the structural changes occurring in the region between the surfactant tails closer to the oil phase, except for the oil-in-water (O/W) micelles region. The study also shows that when each of the sterols is solubilized alone, they occupy different solubilization sites within the microemulsion nanostructures, in comparison to their solubilization together. This behavior is most pronounced in 3:1 (wt. ratio) CH/PS systems. The main conclusion is that co-solubilization of these sterols leads to competitive solubilization between the surfactant tails closer to the oil phase locus, where the CH mols. are pushed toward the interface by the PS mols. This conclusion might better explain the competitive solubilization of the two sterols in the human digestive tract. [on SciFinder(R)]

A major cause of cardiovascular disease is high cholesterol (CH) levels in the blood, a potential soln. to which is the intake of phytosterols (PS) known as CH-reducing agents. One mechanism proposed for PS activity is the mutual cocrystn. of CH and PS from dietary mixed micelles (DMM), a process that removes excess CH from the transporting micelles. In this study, microemulsions (MEs) were used both as a model system for cocrystn. mimicking DMM and as a possible alternative pathway, based on the competitive solubilization of CH and PS, to reduce solubilized CH transport levels from the ME. The effects of different CH/PS ratios, aq. diln., and lecithin-based MEs on sterol crystn. were studied. The pptd. crystals from the ME-loaded system with PS alone and from that loaded with 1:1 or 1:3 CH/PS mixts. were significantly influenced by ME microstructure and by diln. with aq. phase (X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) results). No new polymorphic structures were detected apart from the corresponding sterol hydrates. Mixed crystal morphol. and the habit of the pptd. sterols were strongly affected by the CH/PS ratio and the structures of the dild. ME. As the amt. of PS in the mixt. increased or as the ME aq. diln. proceeded, pptd. crystal shape became more needle-like. The mixed sterols seemed to be forming eutectic solids. [on SciFinder(R)]

A review discusses the selection of food grade ingredients and their acceptable daily intake. Addnl., the procedures and documentation necessary to register new food additives are introduced in view of the issue that additives typically used in controlled released applications are not approved for food products, and therefore need to undergo this registration process. It addresses the regulatory issues regarding the stability of the product, esp. in terms of biol., chem. and phys. stability. It also discusses the regulatory aspects concerning the effectiveness of the formulation. [on SciFinder(R)]

A review discusses the key variable s that det. the effectiveness of the delivery system at different stages of this journey, and the appropriate test methods to evaluate their ability to protect and release the active ingredient. It tackles the different vehicles and encapsulation methodologies currently in use in food products, and pertinent test methods used to validate the prodn. process, and the stability of the product. It then presents the test methods employed to evaluate the in vivo bioavailability of micronutrients and nutraceuticals. Finally, it introduces the issues surrounding the validation of in vitro release test methods, and in particular the aspects surrounding the evaluation of controlled-release formulas. [on SciFinder(R)]

The solubilization of four bioactive mols. with different polarities, in three reverse hexagonal (HII) systems has been investigated. The three HII systems were a typical reverse hexagonal composed of glycerol monooleate (GMO)/tricaprylin/water and two fluid hexagonal systems contg. either 2.75 wt. % Transcutol or ethanol as a fourth component. The phase behavior of the liq. cryst. phases in the presence of ascorbic acid, ascorbyl palmitate, D-$\alpha$-tocopherol and D-$\alpha$-tocopherol acetate were detd. by small-angle X-ray scattering (SAXS) and optical microscopy. Differential scanning calorimetry (DSC) and Fourier-transform IR (FT-IR) techniques were utilized to follow modifications in the thermal behavior and in the vibrations of different functional groups upon solubilizing the bioactive mols. The nature of each guest mol. (in both geometry and polarity) together with the different HII structures (typical and fluids) detd. the corresponding phase behavior, swelling or structural transformations and its location in the HII structures. Ascorbic acid was found to act as a chaotropic guest mol., localized in the water-rich core and at the interface. The AP was also a chaotropic guest mol. with its head located in the vicinity of the GMO headgroup while its tail embedded close to the surfactant tail. D-$\alpha$-tocopherol and D-$\alpha$-tocopherol acetate were incorporated between the GMO tails; however, the D-$\alpha$-tocopherol was located closer to the interface. Once Transcutol or ethanol was present and upon guest mol. incorporation, partial migration was detected. [on SciFinder(R)]

This study reports on the formation of a low viscosity HII mesophase at room temp. upon addn. of Transcutol (diethylene glycol mono Et ether) or ethanol to the ternary mixt. of GMO (glycerol monooleate)/TAG (tricaprylin)/water. The microstructure and bulk properties were characterized in comparison with those of the low viscosity HII mesophase formed in the ternary GMO/TAG/water mixt. at elevated temps. (35-40 °C). We characterized the role of Transcutol or ethanol as inducers of disorder and surfactant mobility. The techniques used were rheol., differential scanning calorimetry (DSC), wide- and small-angle X-ray scattering (WAXS and SAXS, resp.), NMR (self-diffusion and 2H NMR), and Fourier transform IR (FTIR) spectroscopies. The incorporation of either Transcutol or ethanol induced the formation of less ordered HII mesophases with smaller domain sizes and lattice parameters at room temp. (up to 30 °C), similar to those found for the GMO/TAG/water mixt. at more elevated temps. (35-40 °C). On the basis of our measurements, we suggest that Transcutol or ethanol causes dehydration of the GMO headgroups and enhances the mobility of the GMO chains. As a result, these two small mols., which compete for water with the GMO polar headgroups, may increase the curvature of the cylindrical micelles and also perhaps reduce their length. This results in the formation of fluid HII structures at room temp. (up to 30 °C). It is possible that these phases are a prelude to the HII-L2 transformation, which takes place above 35 °C. [on SciFinder(R)]

A review focuses on how the non-lamellar liq. cryst. phase can be turned into well-defined LCNP that can be used to entrap compds. with low aq. soly. as well as hydrophilic compds. It also discusses the stability of the compds. in terms of hydrolysis as well as what happens when these particles interact with an interface. [on SciFinder(R)]

An intermediate mesophase of lyotropic liq. cryst. structure from the ternary mixts. of glycerol monooleate, water, and ethanol was recently characterized in our lab. This mesophase, termed Q L, consists of discrete discontinuous micelles arranged in a cubic array. The Q L phase can solubilize very significant loads of water-insol. anti-inflammatory drug sodium diclofenac (Na-DFC). Close examn. of the internal structures of the lyotropic liq. structure upon increasing the solubilization loads reveals the existence of three structural transitions controlled by the Na-DFC levels. Up to 0.4 wt% Na-DFC, the Q L structure remains intact with some influence on the hydration of the headgroups and on the intermicellar forces. However, at 0.8 to 1.2 wt% Na-DFC, the discontinuous micellar cubic phase is transformed into a more condensed mesophase of a bicontinuous cubic phase. At \textgreater 1.2 wt% Na-DFC, the cubic phase is converted into a lamellar phase (L $\alpha$). Within 5.5 to 7.3 wt% Na-DFC the mesophase is progressively transformed into a less ordered lamellar structure. At ≥ 12 wt% Na-DFC crystals tend to ppt. out. At low Na-DFC concns. the drug behaves like a lyotropic or kosmotropic salt and can salt-out the surfactant from its water layer, but at higher levels it behaves like a hydrotropic, chaotropic salt and can salt-in the surfactant. The Na-DFC location and position within the interface as well as its polarization and partial ionization are strongly affected by its solubilization contents and the structure that it is inducing. In the cubic phase the drug is located less close to the hydration layer while once transition occurs it is exposed more to the water layer and the surfactant headgroups. [on SciFinder(R)]