# All Publications

Idit Amar-Yuli, Ellen Wachtel, Deborah E Shalev, Hagai Moshe, Abraham Aserin, and Nissim. Garti. 2007. “Thermally induced fluid reversed hexagonal (HII) mesophase.” Journal of Physical Chemistry B, 111, 48, Pp. 13544–13553. Abstract
In the present study we characterized the microstructures of the Lc and HII phases in a glycerol monooleate (GMO)/tricaprylin (TAG)/water mixt. as a function of temp. We studied the factors that govern the formation of a low-viscosity HII phase at relatively elevated temps. (\textgreater35°). This phase has very valuable phys. characteristics and properties. The techniques used were 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 reverse hexagonal phase exhibited relatively rapid flow of water in the inner channels within the densely packed cylindrical aggregates of GMO with TAG mols. located in the interstices. The existence of two water diffusion peaks reflects the existence of both mobile water and hydration water at the GMO-water interface (hydrogen exchange between the GMO hydroxyls and water mols.). Above 35°, the sample became fluid yet hexagonal symmetry was maintained. The fluidity of the HII phase is explained by a significant redn. in the domain size and also perhaps cylinder length. This phenomenon was characterized by higher mobility of the GMO, lower mobility of the water, and a significant dehydration process. [on SciFinder(R)]
Marganit Avrahami, Abraham Aserin, and Nissim. Garti. 2007. “Crystallization of Celecoxib in Microemulsion Media.” Journal of Dispersion Science and Technology, 28, 8, Pp. 1228–1235. Abstract
Celecoxib belongs to a new NSAID family specifically inhibiting cyclooxygenase-2 (COX-2). The present formulations require high dosage since the transmembrane transport fluctuates and is very difficult to control. The authors solubilized celecoxib in micelles of nonionic microemulsions and hydrophilic surfactant. The supersatd. solubilized drug was pptd. from the nano-droplets to form a new solid structure with improved dissoln. properties. The selected microemulsion systems loaded with celecoxib were characterized by SAXS, SD-NMR, viscosity, and elec. cond. techniques. Pptn. was conducted from W/O as well as from O/W U-type microemulsions. The crystals obtained by the pptn. were characterized by x-ray powder scattering, differential scanning calorimetry, FTIR measurements, and microscopic scans. [on SciFinder(R)]
Axel Benichou, Abraham Aserin, and Nissim. Garti. 2007. “Oil-in-water-in-oil double emulsions stabilized with WPI-polysaccharide conjugates.” Colloids and Surfaces, A: Physicochemical and Engineering Aspects, 297, 1-3, Pp. 211–220. Abstract
Protein/polysaccharide conjugates were used to stabilize oil-in-water (O/W) emulsions and oil-in-water-in-oil (O/W/O) double emulsions. By properly selecting the type of protein (WPI) and the polysaccharide (xanthan gum, fenugreek gum), and by using specific ratios of the two biopolymers and their soln. concns., amphiphilic biopolymer adducts were formed. A synergism in the emulsification properties was obsd. in WPI/polysaccharide conjugates compared to each of the biopolymers alone. Submicron droplets of oil-in-water were obtained by applying a high-pressure homogenization process during the first step of the double emulsion prepn. It was also demonstrated that double-emulsion globules could be formed with a very high yield of addendum entrapment (above 95%) during the second step of the emulsification process. The differentiation between the two types of oils, O1 (the inner) and O2 (the outer), in the double emulsions enabled high entrapment capacity of the addendum in the inner oil phase. In addn., when the inner oil phase (O1) was a 1:1 (wt./wt.) mixt. of MCT/triacetin and the external oil phase (O2) was a silicone oil, it was possible to slow the release of the entrapped matter while the soly. of the inner phase in the external oil phase remained const. The addendum soly. in the external oil phase was not a limiting factor in the release process. The presence of hydrophobic additives (i.e., 1% glycerol monooleate) in the inner oil phase helped to better control the transport to the external oil phase. In the best case, the addendum leakage to the external oil phase was only ∼0.2% during a period of 28 days at 25°. WPI/xanthan gum adducts served as thick and efficient barriers against release of flumethrin (a veterinary drug model) entrapped in the core of the O/W/O multiple globules. [on SciFinder(R)]
Axel Benichou, Abraham Aserin, Rachel Lutz, and Nissim. Garti. 2007. “Formation and characterization of amphiphilic conjugates of whey protein isolate (WPI)/xanthan to improve surface activity.” Food Hydrocolloids, 21, 3, Pp. 379–391. Abstract
Proteins, polysaccharides and their blends, as examples of natural biopolymers, may be considered as amphiphilic macromolecules that play an essential role in stabilizing food formulations (foams, emulsions and dispersions). Under specific compositions and conditions (protein-to-polysaccharide ratio, pH, ionic strength, temperature, mixing, processing steps) proteins and polysaccharides form water-soluble hybrids (complexes or conjugates), but not coacervates, with enhanced functional properties in comparison to the proteins and polysaccharides alone. Aqueous mixtures of WPI (4-10wt%) and xanthan gum (\textgreater 0.5wt%) form clear aqueous systems exhibiting new physicochemical properties such as rheological behavior, surface properties, surface density of charge (zeta potential), surface hydrophobicity and diffusion behavior. Electrostatic interactions and thermodynamic incompatibility in mixed biopolymer solutions were correlated to the functional properties (rheology, surface properties and surface hydrophobicity) of these adducts. Evidences for associative interactions between WPI and xanthan gum have been established by studying the rheological behavior, the surface hydrophobicity and the surface dynamic properties of the blends. The electrostatic and hydrophobic interactions form hybrids that can provide a synergistic effect on the emulsifying capabilities of the biopolymers and can increase the stability of emulsion droplets against coalescence and flocculation. (c) 2006 Elsevier Ltd. All rights reserved.
Axel Benichou, Abraham Aserin, and Nissim. Garti. 2007. “W/O/W double emulsions stabilized with WPI-polysaccharide complexes.” Colloids and Surfaces, A: Physicochemical and Engineering Aspects, 294, 1-3, Pp. 20–32. Abstract
A synergism in the emulsification properties was seen in WPI/polysaccharide complexes in comparison to each of the biopolymers alone and it was found also to depend on surface properties of the complexes that is strongly affected by the WPI/polysaccharide ratio. It was also demonstrated that the galactose/mannose ratio and the overall no. of galactose residues available on the polysaccharide surface, increasing with the mol. wt. of the mol., strongly influence the surface properties of the blend. At pH below the isoelec. point of WPI/xanthan gum, an increase in the thermal stability of the complex was obsd. and was attributed to strong interactions existing between the biopolymer mols. These adducts served also as thick and efficient barriers against release of Vitamin B1 entrapped in the core of the W/O/W multiple globules. [on SciFinder(R)]
Shmaryahu Ezrahi, Eran Tuval, Abraham Aserin, and Nissim. Garti. 2007. “Daily applications of systems with wormlike micelles.” Surfactant Science Series, 140, Giant Micelles, Pp. 515–544. Abstract
A review. Required properties of wormlike micelles, home-care products (hard surface cleaning,drain opening, paints), personal-care products (hair bleaching/dyeing agents, skin cosmetics) as well as drug delivery products are described. [on SciFinder(R)]
Rivka Efrat, Abraham Aserin, and Nissim. Garti. 2007. “Synergistic solubilization of mixed nutraceuticals in modified discontinuous micellar cubic structures.” Special Publication - Royal Society of Chemistry, 308, Food Colloids, Pp. 87–102 ,302. Abstract
The authors on the solubilization patterns of two of these nutraceuticals (lycopene and phtosteols) which are practically insol. in water but which have been solubilized in the QL (glycerol monooleate (GMO) + ethanol + water) mesophases. The scientific value of these results is threefold. The QL phase has the capability and capacity to solubilize guest mols. of different natures. An anal. method was developed to detect at what concn. levels the guest mols. contribute to the inner order and symmetry of the mesophase, and at what concn. levels they destroy the inner symmetry and cause phase transformations. Certain guest mols. can complement each other structurally at the interface and exhibit synergistic solubilization. [on SciFinder(R)]
Rivka Efrat, Abraham Aserin, Ellina Kesselman, Dganit Danino, Ellen J Wachtel, and Nissim. Garti. 2007. “Liquid micellar discontinuous cubic mesophase from ternary monoolein/ethanol/water mixtures.” Colloids and Surfaces, A: Physicochemical and Engineering Aspects, 299, 1-3, Pp. 133–145. Abstract
In constructing the phase diagram of glycerol monooleate (GMO)/EtOH/H2O mixts. the authors detected, in addn. to the well-characterized regions of lamellar and cubic bicontinuous liq. crystals, 3 addnl. isotropic transparent regions that were not previously well-defined; a large isotropic region denoted in early studies as the L1-phase, an isotropic region with characteristics similar to the sponge L3-phase, and a 3rd isotropic region which had not been characterized previously. The present study deals with efforts to characterize this unique isotropic region. The isotropic region is an island located within a 2 phase region connecting the 3 isotropic regions of the cubic, lamellar, and micellar phases. The authors termed this phase I2 (QL) phase or the QL phase, which stands for cubic liq. mesophase. This phase is a totally transparent and nonbirefringent fluid (completely pourable). It is stable even after over 9 mo of storage at room temp. The fluid is of low viscosity and almost Newtonian. The new phase shows many characteristic features of an ordered phase. Small-angle x-ray scattering measurements (SAXS), SAXS-synchrotron temp.-dependent measurements, and cryogenic-TEM (cryo-TEM) observation reveal that the phase has a cubic symmetry. The SAXS diffractions indicate formation of a somewhat less ordered discontinuous cubic micellar mesophase. The cryo-TEM images provide strong evidence for ordered domains with cubic symmetry. Complementary measurements confirm that the phase is a unique case of a micellar cubic phase. The authors expect that the fluidic ordered mesostructure will have future applications as a liq. vehicle for the solubilization of nutraceuticals, cosmetoceuticals, and pharmaceuticals. [on SciFinder(R)]
Rivka Efrat, Abraham Aserin, Deborah E Shalev, Roy E Hoffman, and Nissim. Garti. 2007. “Effect of drug solubilized in a novel cubic nanostructure.” In Abstracts of Papers, 233rd ACS National Meeting, Chicago, IL, United States, March 25-29, 2007, Pp. COLL–196. American Chemical Society. Abstract
The binary phase diagram of GMO/water reveals the formation of two major lyotropic mesophases that have been extensively studied. Adding short-chain alc. (ethanol, propanol and butanol) to a mixt. of various compns. formed one large isotropic micellar phase (the L phase) and two small confined lyotropic regions termed the L3 sponge phase and the QL (micellar cubic). The QL phase is a new mesostructure. It was shown that while the cubic phase is highly viscous the QL phase is fluid and, it displays unique phys. properties. It is fully transparent (not tinted), non-birefringent, and very stable at room temp. (samples were stored for over 8 mo with no phys. changes). The phases were investigated by cryo-TEM, SAXS and self-diffusion NMR. The structure it has primitive cubic symmetry and is discontinuous micellar phases rather than a bicontinuous one. The QL phase was further dispersed in water contg. amphiphilic copolymer (Pluronic 127) to form cubic nanoparticles that we termed micellosomes. The effect of solubilization of water-insol. drugs like, diclofenc (DCF), at different concns. (0.1, 1, 3, and 10 wt%) in the QL phase was investigated by SAXS, rheol. measurements, and NMR (self-diffusion and relaxation) measurements. The rate of percutaneous penetration through rat skin of these structures is significantly higher than that of the com. drug. The compn. that shows the best penetration was QL with 1 wt% DCF. [on SciFinder(R)]
N Garti and A Aserin. 2007. “Nanoscale liquid self-assembled dispersions in foods and the delivery of functional ingredients.” In Understanding Controlling Microstruct. Complex Foods, edited by D.J. McClements, Pp. 504–553. Woodhead Publishing Ltd. Abstract
A review. It discusses characteristics of liq. dispersions that provide the food industry with some unique advantages that cannot be obtained using other technologies. It also reviews the phys., chem., and biol. properties of the nanoscale architectures that are substantially different from their macroscopic counterparts. [on SciFinder(R)]
Nissim. Garti. 2007. “Cosmetoceuticals in modified microemulsions.” Surfactant Science Series, 135, Surfactants in Personal Care Products and Decorative Cosmetics (3rd Edition), Pp. 211–234. Abstract
A review. A novel technol. to prep. modified reverse microemulsion (denoted NSSL, nanosized self-assembled liq.) vehicles loaded with cosmetoceuticals, based on permitted ingredients that can be progressively dild. with water, was developed recently in our labs. The microemulsion isotropic regions representing water-in-oil (W/O), bicontinuous mesophase, and oil-in-water (O/W) microemulsion structures are presented in a phase diagram so-called U-type. In such compns. in the isotropic regions of the phase diagram, structures can invert from L2 (reverse micelles) to an L1 (direct micelles) phase via W/O, bicontinuous, and O/W regions progressively, without phase sepn. The concs. (condensed reverse micelles) can be loaded at very high solubilization capacities of guest mols. (lycopene, phytosterols, tocopherols, CoQ10, lutein, antioxidants, aromas, fragrances) that are oil sol. or even mostly insol. in the water or oil phase. The solubilization exceeds manyfold that of the soly. capacity of each of the phases. The microemulsion phase transformations were studied by cond., viscosity differential scanning calorimetry (DSC), and self-diffusion-NMR (SD-NMR) measurements, and the microstructure was detd. by small-angle x-ray scattering (SAXS), cryo-transmission electron microscopy (TEM). The loci of the solubilizate at any given water content were detd. by following the self-diffusion coeffs. of each of the ingredients. It was concluded that the solubilizates are easily accommodated and tightly packed at the concave, hydrophobic-in-nature, water-in-oil interface and at the bicontinuous interface. Most solubilizates are more loosely packed at the oil-in-water interface and tend to be released from the interface once inversion occurs. Upon inversion to O/W microemulsion droplets, the interface becomes more hydrophilic and convexes toward the water, becoming the continuous phase. The solubilization capacity drops dramatically, and the active matter can be trigger released. The nutraceuticals are solubilized at higher solubilization capacities if interacting with the surfactant. Upon entrapping guest mols., the transition from W/O to bicontinuous, and thereafter to an O/W microemulsion, is occurring, in some cases, at higher levels of water diln., while in other cases, depending on the nature of the solubilizate, at lower dilns., indicating that some of the guest compds. add some order to the internal microemulsion organization, while others are destructive to the interface and enhance phase sepn. or phase transitions. [on SciFinder(R)]
The invention relates to a nucleating microemulsion comprising nanovehicles, each comprising an amphiphilic shell surrounding a nucleating agent. The microemulsion is suitable for delivery of the nucleating agents into a thermoplastic polymer, thereby allowing crystn. of the polymer. A method for crystg. and increasing the nucleation efficiency of a thermoplastic polymer comprises dispersing the above nucleating microemulsion in a thermoplastic polymer melt. The polymer compns. contg. the nucleating microemulsions can be used for prodn. of plastic films, fibers, boards, sheets, articles, packaging materials, containers, pipes, medical goods, sporting goods, labware, dinnerware, and cookware. [on SciFinder(R)]
Novel interfacial crystallization technique to obtain drugs polymorphes controlled by the microemulsions interfaces.
Nissim Garti and Rivka. Efrat. 2007. “Micellar cubic structures, QL, and micellosomes for improved solubilization and bioavailability on nutraceuticals.” In Abstracts of Papers, 233rd ACS National Meeting, Chicago, IL, United States, March 25-29, 2007, Pp. AGFD–127. American Chemical Society. Abstract
Polar lipid mols. such as glycerol monooleate (GMO) and polar solvent (usually water) can spontaneously organize in high order at the long-range distances while in the short-range, at at. distances, they are disordered. Liq. cryst. mesophases with a long-range order in one dimension are lamellar phases (L$\alpha$ ) while those showing two dimensional long-range order are known as hexagonal phases (HI and H2 for normal and reverse hexagonal) and those with three dimension long-range orders are lyotropic cubic phase (C). Hydrophobic effect with a variety of intra- and intermol. interactions, in combination with a no. of geometric packing constraints, are responsible for the degree of order. Addn. of guest mols. (solubilizates) to the liq. crystals can alter the structure according to specific mol. interaction between the GMO and the guest compd. that contributes to the surface area species. In our recent studied we have discovered that ternary blends of GMO, water and cosolvent can form unique structures. The focus of this presentation is on a new mesophase that was formed as a result of phase transformations. The new structure was eluted from lamellar, cubic, and hexagonal isotropic liq. phases in ternary systems. The new phase, termed by us the QL mesophase, is very unique since it is transparent liq. phase with long-range order. The QL phase was studied by small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), self-diffusion NMR, DSC and cond. methods. The unique rheol. properties of a system totally fluid and yet non Newtonian will be discussed in view of the suggested structure of micellar discontinuous cubic phase. Microstructure data as well as solubilization data of several nutraceuticals mols. and their bioavailability advantages will be presented. [on SciFinder(R)]
Nissim Garti, Eli Pinthus, Abraham Aserin, and Aviram. Spernath. 2007. “Improved solubilization and bioavailability of nutraceuticals in nanosized self-assembled liquid vehicles.” In Encapsulation Controlled Release Technol. Food Syst., Pp. 13–40. Blackwell Publishing Professional. Abstract
A review discusses the development of modified microemulsions as nanosized self-assembled liq. (NSSL) vehicles for the solubilization of nutraceuticals and to improve transmembrane transport for addnl. health benefits. The solubilization of nonsol. active ingredients such as aromas and antioxidants into clear beverages that are based on water-continuous phase is presented. [on SciFinder(R)]
Anna Kogan, Abraham Aserin, and Nissim. Garti. 2007. “Improved solubilization of carbamazepine and structural transitions in nonionic microemulsions upon aqueous phase dilution.” Journal of Colloid and Interface Science, 315, 2, Pp. 637–647. Abstract
Solubilization capacity and structural transformations in nonionic microemulsions characterized by a large continuous isotropic region forming dilutable self-assembled nanodroplets contg. solubilized carbamazepine, were studied along diln. lines 73 and 82 (70 and 80% surfactant and 30 and 20% of oil phase, resp.). The prepns. were based on pharma-grade ingredients, water, R-(+)-limonene, ethanol, propylene glycol, and Tween 60. Solubilization capacity (SC) of the drug was dependent on the microstructure of the microemulsion and on the surfactant-to-oil phase wt. ratio. The SC in the conc. (reversed micelles) was 15 times higher than its soly. in the oil. Transition of the W/O microemulsion to a bicontinuous phase and to O/W droplets were identified by elec. cond., viscosity, SAXS, and SD-NMR measurements. Once the system is dild. to 90% aq. phase, the SC is 10 and 16-fold higher, along diln. lines 73 and 82, resp., than in pure water. Being solubilized, carbamazepine serves as a cosurfactant therefore it affects the curvatures of the microstructures and consequently the boundaries of the structural regions and the transition points between the different phases. Dilutable microemulsions are promising new carbamazepine vehicles for oral intake. [on SciFinder(R)]