All Publications

Rachel Lutz, Abraham Aserin, Louise Wicker, and Nissim. Garti. 2009. “Release of electrolytes from W/O/W double emulsions stabilized by a soluble complex of modified pectin and whey protein isolate.” Colloids and Surfaces, B: Biointerfaces, 74, 1, Pp. 178–185. Abstract
W/O/W double emulsions (DEs) stabilized by charged sol. complexes of whey protein isolate (WPI) and modified pectins were investigated in relation to their stability and the release of two types of electrolytes, NaCl and sodium ascorbate. WPI alone cannot properly stabilize the DEs. The droplet size is relatively large (100 $μ$m) and increases with time. However, addn. of modified pectin to form a sol. complex with WPI significantly improved the stability. DEs prepd. with two types of oils (medium chain triglycerides (MCT) and R(+)-limonene) were studied by measuring droplet size, creaming, viscosity, and electrolyte release. Irresp. of their very different oil phase nature, both emulsions were stable against coalescence, but R(+)-limonene formed smaller droplets (25 $μ$m) than MCT (35 $μ$m). The electrolyte release rate was significantly higher from the R(+)-limonene that formed DEs with much lower viscosity. R(+)-limonene-DE released 75% of the NaCl after 28 days, while MCT-DE released only 50%. NaCl was released more slowly than sodium ascorbate. Apparently, the release mechanism from R(+)-limonene-DE was found to be "thinning the outer interface and release of the entire inner droplets" while it seems that the release from MCT-DE was slower and "diffusion controlled". DEs stabilized by WPI/C63 released 12% of the sodium ascorbate after 1 day in milk and remained stable for at least 8 days. However, DEs stabilized with only WPI released about 50% of the sodium ascorbate after 1 day, and phase sepd. after 8 days. [on SciFinder(R)]
Dima Libster, Paul Ben Ishai, Abraham Aserin, Gil Shoham, and Nissim. Garti. 2009. “Molecular interactions in reverse hexagonal mesophase in the presence of cyclosporin A.” International Journal of Pharmaceutics, 367, 1-2, Pp. 115–126. Abstract
The present work investigates the detailed mol. structure of the HII mesophase of glycerol monooleate (GMO) /tricaprylin/phosphatidylcholine/water system in the presence of hydrophobic model peptide cyclosporin A (CSA) via ATR-FTIR anal. The conformation of the peptide in the hexagonal mesophase, as well as its location and specific interactions with the components of the carrier, were studied. Incorporation of phosphatidylcholine to the ternary GMO/tricaprylin/water system caused competition for water binding between the hydroxyl groups of GMO and the phosphate groups of the phosphatidylcholine (PC) leading to dehydration of the GMO hydroxyls in favor of phospholipid hydration. Anal. of CSA solubilization effect on the HII mesophase revealed a significant increase in the strength of hydrogen bonding with surfactant hydrogen-bonded carbonyls, indicating interaction of the peptide with the C=O groups of the surfactants. The peptide probably caused partial replacement of the intramol. hydrogen bonds of the mesophase carbonyl groups with intermol. hydrogen bonds of these carbonyl groups with the peptide. Furthermore, anal. of the Amide I' peak in the FTIR spectra of the peptide demonstrated that two pairs of its internal hydrogen bonds are disrupted when it is incorporated. The partial disruption of the internal hydrogen bonds seems to cause an outward rotation of the peptide amide groups involved, resulting in more efficient intermol. hydrogen-bonding ability. Apparently, this conformational change increased the hydrophilic properties of CSA, even making it susceptible to a weak interaction with the GMO hydroxyl groups in the interfacial region. [on SciFinder(R)]
R Lutz, A Aserin, L Wicker, and N Garti. 2009. “Structure and physical properties of pectins with block-wise distribution of carboxylic acid groups.” Food Hydrocolloids, 23, 3, Pp. 786–794. Abstract
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.
Dima Libster, Abraham Aserin, Doron Yariv, Gil Shoham, and Nissim. Garti. 2009. “Concentration- and temperature-induced effects of incorporated desmopressin on the properties of reverse hexagonal mesophase.” Journal of Physical Chemistry B, 113, 18, Pp. 6336–6346. Abstract
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)]
Rachel Lutz, Abraham Aserin, Louis Wicker, and Nissim. Garti. 2009. “Double emulsions stabilized by a charged complex of modified pectin and whey protein isolate.” Colloids and Surfaces, B: Biointerfaces, 72, 1, Pp. 121–127. Abstract
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)]
Shoshana Rozner, Anna Kogan, Somil Mehta, Ponisseril Somasundaran, Abraham Aserin, Nissim Garti, and Maria Francesca. Ottaviani. 2009. “Characterization of Nonionic Microemulsions by EPR. Part II. The Effect of Competitive Solubilization of Cholesterol and Phytosterols on the Nanostructure.” Journal of Physical Chemistry B, 113, 3, Pp. 700–707. Abstract
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)]
Shoshana Rozner, Inna Popov, Vladimir Uvarov, Abraham Aserin, and Nissim. Garti. 2009. “Templated cocrystallization of cholesterol and phytosterols from microemulsions.” Journal of Crystal Growth, 311, 16, Pp. 4022–4033. Abstract
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)]
E Acosta. 2008. “Regulatory aspects of nutrient delivery systems.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 429–449. Woodhead Publishing Ltd. Abstract
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)]
E Acosta. 2008. “Testing the effectiveness of nutrient delivery systems.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 53–106. Woodhead Publishing Ltd. Abstract
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)]
Idit Amar-Yuli, Abraham Aserin, and Nissim. Garti. 2008. “Solubilization of Nutraceuticals into Reverse Hexagonal Mesophases.” Journal of Physical Chemistry B, 112, 33, Pp. 10171–10180. Abstract
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)]
Idit Amar-Yuli, Ellen Wachtel, Deborah E Shalev, Abraham Aserin, and Nissim. Garti. 2008. “Low Viscosity Reversed Hexagonal Mesophases Induced by Hydrophilic Additives.” Journal of Physical Chemistry B, 112, 13, Pp. 3971–3982. Abstract
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)]
J Barauskas and T Nylander. 2008. “Lyotropic liquid crystals as delivery vehicles for good ingredients.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 107–131. Woodhead Publishing Ltd. Abstract
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)]
R Efrat, A Aserin, and N Garti. 2008. “On structural transitions in a discontinuous micellar cubic phase loaded with sodium diclofenac.” Journal of Colloid and Interface Science, 321, 1, Pp. 166–176. Abstract
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)]