Publications

2008
Dima Libster, Ben Ishai, Paul , Aserin, Abraham , Shoham, Gil , and Garti, Nissim. . 2008. From The Microscopic To The Mesoscopic Properties Of Lyotropic Reverse Hexagonal Liquid Crystals.. Langmuir, 24, 5, Pp. 2118–2127. doi:10.1021/la702570v.
The authors aimed to explore a correlation between the microstructural properties of the lyotropic reverse hexagonal phase (HII) of the GMO/tricaprylin/phosphatidylcholine/H2O system and its mesoscopic structure. The mesoscopic organization of discontinuous and anisotropic domains was examd., in the native state, using environmental SEM. The topog. of the HII mesophases was imaged directly in their hydrated state, as a function of aq.-phase concn. and compn., when a proline amino acid was solubilized into the systems as a kosmotropic (water-structure maker) guest mol. The domain structures of several dozen micrometers in size, visualized in the environmental SEM, possess fractal characteristics, indicating a discontinuous and disordered alignment of the corresponding internal H2O rods on the mesoscale. On the microstructural level, SAXS measurements revealed that as H2O content (Cw) increases the characteristic lattice parameter of the mesophases increases as well. Using the H2O concn. as the mass measure of the mixts., a scaling relation between the lattice parameter and the concn. was found to obey a power law whereby the derived fractal dimension was the relevant exponent, confirming the causal link between the microscopic and mesoscopic organizations. The topog. of the HII mesophase is affected by the microstructural parameters and the compn. of the samples. Thermal anal. expts. involving these systems further confirmed that the behavior of H2O underpins both microscopical and mesoscopic features of the systems. Both the swelling of the lattice parameter and the mesoscopic domains is correlated to the bulk H2O concn. in the H2O rods. [on SciFinder(R)]
N Garti. 2008. The Future Of Controlled Release And Delivery Technologies.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 450–464. Woodhead Publishing Ltd. doi:10.1533/9781845694210.4.450.
A review. In some countries health authorities are advising minimizing the use of insol. solid nanoparticles that have been shown to cause some significant damage to the healthy growth of various cells and to decrease the viability of others. However, companies and those dealing with future foods prefer to conc. on delivery methods and technologies and to refrain from using the term nanosized particles. All the technologies will involve utilization of new encapsulation and entrapment of bioactives and other food additives by advanced encapsulation micro- and nanovehicles. [on SciFinder(R)]
Roy E Hoffman, Arzuan, Hilla , Pemberton, Chava , Aserin, Abraham , and Garti, Nissim. . 2008. High-Resolution Nmr "Chromatography" Using A Liquids Spectrometer.. Journal Of Magnetic Resonance, 194, 2, Pp. 295–299. doi:10.1016/j.jmr.2008.06.022.
NMR spectroscopy is an excellent tool for the structural anal. of pure compds. However, for mixts. it performs poorly because of overlapping signals. Diffusion can be used to sep. compds. of widely differing mol. wt. but the amt. of sepn. is usually insufficient. Addn. of a solid medium, analogous to the stationary phase in chromatog., can preferentially slow the diffusion of some components of a mixt. permitting sepn. in the diffusion dimension. However, this would usually require a solid-state NMR spectrometer otherwise the signals would be too broad. Susceptibility matching the solvent to the solid medium yields a spectrum with narrow signals allowing the measurement of a DOSY spectrum with enhanced sepn. in the diffusion dimension. [on SciFinder(R)]
Rachel Lutz, Pikarek, Hagit , Aserin, Abraham , and Garti, Nissim. . 2008. Hydrocolloids In Relation To Their Emulsification Activity - Wpi/Hydrocolloid Complexes.. Foods & Food Ingredients Journal Of Japan, 213, 3, Pp. 216–228.
The present manuscript is in two parts. In the first part we characterize a new sol. complex (hybrid) formed in aq. soln. from WPI and the hydrocolloids (xanthan, pectin, and LBG), while in the second we demonstrate the advantage of the complexes as amphiphilic biopolymers utilized for steric and depletion stabilization of emulsions and multiple emulsions. It was found that the major factor affecting the formation of a sol. complex (hybrid) of the WPI and the hydrocoltoids is the intermol. charge interactions and not the Mw of the two biopolymers. The best concn. and ratio of WPI and the hydrocolloids (pectin and xanthan) to form the sol. complex are 4 wt% WPI and 0.5-1.0 wt% of the hydrocolloids. The interactions are between some mol. pos. charged patches on the protein and neg. charged fractions of the hydrocolloids. The WPI/hydrocolloid complex can provide good steric stabilization to the external interface of an emulsion and double emulsion. The droplets stabilized with the complex are smaller than those stabilized with WPI alone. Good creaming stability was also obtained. [on SciFinder(R)]
S Rozner, Verkhovski, L, Nissimov, Y, Aserin, A, Vilensky, R, Danino, D, Zouboulis, CC, Milner, Y, and Garti, N. 2008. Inhibition Of Cholesterol Transport Into Skin Cells In Cultures By Phytosterol-Loaded Microemulsion.. Chemistry And Physics Of Lipids, 153, 2, Pp. 109–118. doi:10.1016/j.chemphyslip.2008.02.017.
Cholesterol and plant phytosterols are lipophilic compds. solubilized by intestinal micelles in a competitive manner. In this work, we used radioactive cholesterol- and phytosterol-loaded oil-in-water microemulsions to follow their incorporation and mutual competition in HaCaT keratinocytes, SZ95 sebocytes, and skin pieces in cultures. Dynamic light scattering showed homogeneous nanostructures of 10.5 ± 1.5 nm diam. and cryo-transmission electron microscopy confirmed the presence of uniform spherical droplets of 7.0 ± 1.0 nm diam. Up to 320 nmol/mL of cholesterol can be solubilized and transported into cells with minimal toxic effect by 0.5 wt.% nanodroplets in a cell medium. Phytosterols inhibit incorporation of cholesterol into cells, in vitro, at molar ratios (phytosterols/cholesterol) of 4 and above. The loaded nanodroplets accumulate in intracellular vesicles (presumably endosomes). No metabolic conversion of cholesterol or phytosterols was found in these cells, in vitro, after 24 h, at 37°. [on SciFinder(R)]
O Ramon and Danino, D. 2008. Lipid Self-Assembled Particles For The Delivery Of Nutraceuticals.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 207–233. Woodhead Publishing Ltd. doi:10.1533/9781845694210.2.207.
A review discusses the principles of lipid self-assembling systems, their integration in the mainframe of the packing concept of Israelachvili and coworkers, thermodn. constraints, and physico-chem. properties. [on SciFinder(R)]
J Barauskas and Nylander, T. 2008. Lyotropic Liquid Crystals As Delivery Vehicles For Good Ingredients.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 107–131. Woodhead Publishing Ltd. doi:10.1533/9781845694210.1.107.
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)]
N Garti and Yuli-Amar, I. 2008. Micro- And Nano-Emulsions For Delivery Of Functional Food Ingredients.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 149–183. Woodhead Publishing Ltd. doi:10.1533/9781845694210.2.149.
A review discusses the impact of the nanotechnol. on food preservation, food quality, and on nutrition and health aspects. [on SciFinder(R)]
Aviram Spernath, Aserin, Abraham , Sintov, Amnon C, Garti, Nissim. , Spemath, Aviram , Aserin, Abraham , Sintov, Amnon C, and Garti, Nissim. . 2008. Phosphatidylcholine Embedded Micellar Systems: Enhanced Permeability Through Rat Skin. Journal Of Colloid And Interface Science, 318, 2, Pp. 421–429. doi:10.1016/j.jcis.2007.10.036.
Micellar and microemulsion systems are excellent potential vehicles for delivery of drugs because of their high solubilization capacity and improved transmembrane bioavailability. Mixts. of propylene glycol (PG) and nonionic surfactants with sodium diclofenac (DFC) were prepd. in the presence of phosphatidylcholine (PC) as transmembrane transport enhancers. Fully dilutable systems with max. DFC solubilization capacity (SC) at pH 7 are presented. It was demonstrated that the concs. underwent phase transitions from reverse micelles to swollen reverse micelles and, via the bicontinuous transitional mesophase, into inverted O/W microstructures. The SC decreases as a function of diln. DFC transdermal penetration using rat skin in vitro correlated with SC, water content, effect of phospholipid content, presence of an oil phase, and ethanol. Skin penetration from the inverted bicontinuous mesophase and the skin penetration from the O/W-like microstructure were higher than that measured from the W/O-like droplets, esp. when the micellar system contg. the nonionic surfactant, sugar ester L-1695, and hexaglycerol laurate. PC embedded within the micelle interface significantly increased the penetration flux across the skin compared to micellar systems without the embedded PC at their interface. Moreover, the combination of PC with HECO40 improved the permeation rate (P) and shortened the lag-time (TL). [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. doi:10.1533/9781845694210.4.429.
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)]
Idit Amar-Yuli, Aserin, Abraham , and Garti, Nissim. . 2008. Solubilization Of Nutraceuticals Into Reverse Hexagonal Mesophases.. Journal Of Physical Chemistry B, 112, 33, Pp. 10171–10180. doi:10.1021/jp802737k.
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)]
R Efrat, Aserin, A, and Garti, N. 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. doi:10.1016/j.jcis.2008.01.013.
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)]
E Acosta. 2008. Testing The Effectiveness Of Nutrient Delivery Systems.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 53–106. Woodhead Publishing Ltd. doi:10.1533/9781845694210.1.53.
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)]
Nissim Garti. 2008. Delivery And Controlled Release Of Bioactives In Foods And Nutraceuticals Preface. In , Pp. 478pp. UK: Woodhead Publishing Ltd.
Idit Amar-Yuli, Wachtel, Ellen , Shalev, Deborah E, Aserin, Abraham , and Garti, Nissim. . 2008. Low Viscosity Reversed Hexagonal Mesophases Induced By Hydrophilic Additives.. Journal Of Physical Chemistry B, 112, 13, Pp. 3971–3982. doi:10.1021/jp711421k.
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)]
G Lafitte. 2008. Structure Of The Gastrointestinal Mucus Layer And Implications For Controlled Release And Delivery Of Functional Food Ingredients.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 26–52. Woodhead Publishing Ltd. doi:10.1533/9781845694210.1.26.
A review discusses the compn. and the properties of the mucin mols. and the mechanism of adhesion of delivery vehicles to the mucus layer. The efficiency of a controlled-release formulation is subjected to the balance between the kinetics of its adhesion and the rate of erosion of the mucus. The influence of some of the mucin mols. and lipids is discussed. [on SciFinder(R)]
Nissim Garti, Aserin, Abraham , and Hoffman, Roy. . 2008. System And Methods For Diffusion Ordered Spectroscopy..
The invention relates to a method for generating liq.-state diffusion order NMR spectroscopy (DOSY), method for minimizing the peak width in liq.-state DOSY, method of enhancing the sepn. between diffusion coeff. of compds. in liq.-state DOSY, a method for prepg. a system for generating liq.-state diffusion ordered DOSY of a sample, a method for prepg. a system for generating a liq.-state DOSY of a sample and kits for carrying liq.-state DOSY. [on SciFinder(R)]
Anna Kogan, Kesselman, Ellina , Danino, Dganit , Aserin, Abraham , and Garti, Nissim. . 2008. Viability And Permeability Across Caco-2 Cells Of Cbz Solubilized In Fully Dilutable Microemulsions.. Colloids And Surfaces, B: Biointerfaces, 66, 1, Pp. 1–12. doi:10.1016/j.colsurfb.2008.05.006.
The viability and permeability of carbamazepine (CBZ) solubilized in fully dilutable non-ionic microemulsions across Caco-2 cells used as a model for intestinal epithelium. Maximum solubilization capacity (SC) of CBZ was detd. within water-in-oil (W/O), bicontinuous and oil-in-water (O/W) structures formed upon diln. The effect of the nature of the oil phase, surfactant type, and the ratio between the oil phase and surfactant on the quantity of solubilized CBZ, droplets size, the viability of the cells and drug permeability was elucidated. Several fully dilutable microemulsions based on pharma-grade ingredients can be loaded with very significant amts. of CBZ, and W/O microemulsions (10 wt% water) exhibit up to 3-fold higher solubilization capacity over the drug's soly. in oil (triacetin). CBZ in the O/W microemulsions (80 wt% water) exhibit up to 29-fold higher solubilization than in water, and the O/W droplets of the examd. systems are 9-11 nm in size, and the highest permeability was obtained in systems contg. triacetin/$\alpha$-tocopherol acetate/ethanol in 3/1/4 wt% ratio as oil phase and Tween 60 as surfactant. The replacement of $\alpha$-tocopherol acetate by $\alpha$-tocopherol inhibits CBZ release and replacement of a satd. chain of Tween 60 by an unsatd. (Tween 80) or shorter chain (Tween 40) inhibited drug release. The decrease in the oil phase to surfactant ratio leads to enhancement of drug release (diln. line 64 \textgreater diln. line 73). [on SciFinder(R)]
2007
Dima Libster, Aserin, Abraham , and Garti, Nissim. . 2007. Advanced Nucleating Agents For Polypropylene.. Polymers For Advanced Technologies, 18, 9, Pp. 685–695. doi:10.1002/pat.970.
The present short review aims to summarize advanced nucleating agents for polypropylene (PP). Reviewing the relevant literature, we focused on powerful nucleators that are capable of significantly increasing the crystn. temp. of the polymer at very low working concns. and also serving as clarifying agents. The nucleation mechanism and efficiency of these compds. are discussed in detail. The nucleating agents were divided into groups according to their tendency to induce monoclinic ($\alpha$), hexagonal ($\beta$), or orthorhombic ($\gamma$) PP cell geometries. The major $\alpha$-nucleators and clarifiers are sorbitol-based compds. that speed-up the polymer crystn. due to gelation phenomena and induction of epitaxial crystn. by the metal salts of substituted arom. heterocyclic phosphate. Among $\beta$-nucleators, N,N'-dicyclohexyl-2,6-naphthalene dicarboxamide was found to be very efficient and its nucleation ability was highly concn. dependent. In addn., it was shown that nucleation efficiency of a nucleator can be significantly increased by a new dispersion method comprising its solubilization in a microemulsion. Moreover, the nucleator (HPN-68) increased the $\gamma$-modification present in the polymer. [on SciFinder(R)]

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