# Peer Review Publications

Dima Libster, Paul Ben Ishai, Abraham Aserin, Gil Shoham, and Nissim. Garti. 2008. “From the Microscopic to the Mesoscopic Properties of Lyotropic Reverse Hexagonal Liquid Crystals.” Langmuir, 24, 5, Pp. 2118–2127. Abstract
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)]
A Millqvist-Fureby. 2008. “Encapsulation approaches for proteins.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 404–425. Woodhead Publishing Ltd. Abstract
A review discusses solid formulations for proteins, and in particular how spray drying can be used to encapsulate bioactive materials in solid formulations, and the application of polyelectrolyte multilayer microcapsules to protein encapsulation in liq. formulations. [on SciFinder(R)]
Rachel Lutz, Hagit Pikarek, Abraham Aserin, and Nissim. Garti. 2008. “Hydrocolloids in relation to their emulsification activity - WPI/hydrocolloid complexes.” Foods & Food Ingredients Journal of Japan, 213, 3, Pp. 216–228. Abstract
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)]
Shoshana Rozner, Abraham Aserin, and Nissim. Garti. 2008. “Competitive solubilization of cholesterol and phytosterols in nonionic microemulsions studied by pulse gradient spin-echo NMR.” Journal of Colloid and Interface Science, 321, 2, Pp. 418–425. Abstract
The actual mechanism of cholesterol redn. by phytosterols is yet to be explored. One hypothesis states that cholesterol and phytosterols compete on the solubilization locus within gastric bile salt micelles. In this study competitive solubilization within microemulsions as vehicles for dietary intake of cholesterol and phytosterols was studied by pulse gradient spin-echo NMR. The loaded microemulsions undergo phase transitions as a function of diln., the type of solubilized sterol, and the wt. ratio of the cosolubilized sterols. Microemulsions contg. 10-20 wt% of aq. phase, show similar diffusivity of the oil and aq. phases in all examd. systems (excluding PS-loaded one) reflecting the minor influence of these solubilizates on the structure of the inner and the outer phases. The closeness of these structures enables the mobility of water mols. between them. Upon further diln. (\textgreater20 wt% aq. phase), significant differences in decrease rate of the oil and increase of the water phases mobilities (occurring upon inversion), were detected within the studied systems. It was concluded that the solubilized sterols influence the structural transitions based on their location within the structures and their competitive solubilization. The phytosterols solubilized mostly in the continuous oil phase and between the surfactant tails. Cholesterol is solubilized in the vicinity of the surfactant headgroups and affects the surface curvature. In mixts. of cholesterol and phytosterols, structural changes are dictated mostly by the presence of the cholesterol. [on SciFinder(R)]
CM Sabliov and CE Astete. 2008. “Encapsulation and controlled release of antioxidants and vitamins.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 297–330. Woodhead Publishing Ltd. Abstract
A review discusses the importance of antioxidants to human health, advantages of nanoencapsulation of these components over traditional delivery methods. Top-down techniques available to entrap antioxidants and vitamins in biodegradable and biocompatible polymeric nanoparticles are discussed, methods available for polymeric nanoparticle characterization are briefly mentioned, and some insights on the release profile of antioxidants and vitamins from polymeric nanoparticles are presented. [on SciFinder(R)]
O Ramon and D Danino. 2008. “Lipid self-assembled particles for the delivery of nutraceuticals.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 207–233. Woodhead Publishing Ltd. Abstract
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)]
S Rozner, L Verkhovski, Y Nissimov, A Aserin, R Vilensky, D Danino, CC Zouboulis, Y Milner, and N Garti. 2008. “Inhibition of cholesterol transport into skin cells in cultures by phytosterol-loaded microemulsion.” Chemistry and Physics of Lipids, 153, 2, Pp. 109–118. Abstract
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)]
Aviram Spernath, Abraham Aserin, Amnon C Sintov, Nissim. Garti, Aviram Spemath, Abraham Aserin, Amnon C Sintov, and Nissim. Garti. 2008. “Phosphatidylcholine embedded micellar systems: Enhanced permeability through rat skin.” JOURNAL OF COLLOID AND INTERFACE SCIENCE, 318, 2, Pp. 421–429. Abstract
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)]
Marina Shevachman, Nissim Garti, Arnon Shani, and Amnon C Sintov. 2008. “Enhanced Percutaneous Permeability of Diclofenac Using a New U-Type Dilutable Microemulsion.” Drug Development and Industrial Pharmacy, 34, 4, Pp. 403–412. Abstract
Enhanced systemic absorption in vivo and percutaneous penetration in vitro was demonstrated after transdermal administration of diclofenac sodium formulated in U-type microemulsion. Diclofenac sodium was solubilized in a typical four-component system consisting of an oil, polyoxyethylene-10EO-oleyl alc. (Brij 96V) as the surfactant, and 1-hexanol along water diln. line W46 (40 wt. % surfactant and 60 wt. % oil phase before water titrn.). Viscosity and small angle x-ray scattering measurements have evidenced bicontinuous structures within water fractions of 0.25 and 0.5 along the diln. line. Self-diffusion NMR studies showed that drug mols. accumulated in the interfacial film and, to some extent, dissolved in the oil. Relative to a com. macro-emulsion cream (Voltaren Emulgel), microemulsions contg. paraffin oil or iso-Pr myristate increased the in vivo transdermal penetration rate of diclofenac by two order of magnitude, whereas the rat plasma levels were increased by one order of magnitude. The in vitro data obtained from excised rat skin were comparable to the in vivo results, but suffered from discrepancies from the ideal in vivo-in vitro correlation, which might be explained by optimal in vitro conditions of perfusion and hydration. It has also been found that when jojoba oil is formulated as the oil phase in the microemulsion, the penetration rate of the drug decreases significantly. Based on the three-dimensional structure of jojoba oil, the wax is presumed to prevent the drug from being freely diffused into the skin while migrating from the interfacial film into the continuous oil phase. [on SciFinder(R)]
LA Shaw, H Faraji, T Aoki, D Djordjevic, DJ McClements, and EA Decker. 2008. “Emulsion droplet interfacial engineering to deliver bioactive lipids into functional foods.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 184–206. Woodhead Publishing Ltd. Abstract
A review. When bulk $ømega$-3 oils are added to foods, the oil will no longer be in a bulk form but will instead exist as an oil-in-water or water-in-oil dispersion. Most omega-3 oil processors add polar antioxidants to protect their bulk oil against oxidn. during storage. However, when the oil is then dispersed into foods, these antioxidants can partition into the aq. phase where they are ineffective and can be potentially prooxidative due to their ability to make transition metals more prooxidative. Use of oil-in-water emulsions to deliver $ømega$-3 fatty acids into functional foods may provide an alternative to bulk oils. [on SciFinder(R)]
M Subirade and L Chen. 2008. “Food-protein-derived materials and their use as carriers and delivery systems for active food components.” In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 251–278. Woodhead Publishing Ltd. Abstract
A review illustrates the potential of food protein-based matrixes to serve as carriers for the controlled release of functional food components. It focuses on recent progress in the design, prepn. and evaluation of food-protein-based delivery systems based on hydrogel or micro- and nanoparticles and their potential for the development of innovative functional foods. [on SciFinder(R)]
Idit Amar-Yuli, Ellen Wachtel, Einav Ben hoshan, Dganit Danino, Abraham Aserin, and Nissim. Garti. 2007. “Hexosome and Hexagonal Phases Mediated by Hydration and Polymeric Stabilizer.” Langmuir, 23, 7, Pp. 3637–3645. Abstract
In this research, we studied the factors that control formation of GMO/tricaprylin/water hexosomes and affect their inner structure. As a stabilizer of the soft particles dispersed in the aq. phase, we used the hydrophilic nonionic triblock polymer Pluronic 127. We demonstrate how properties of the hexosomes, such as size, structure, and stability, can be tuned by their internal compn., polymer concn., and processing conditions. The morphol. and inner structure of the hexosomes were characterized by small-angle x-ray scattering, cryo-transmission electron microscope, and dynamic light scattering. The phys. stability (to creaming, aggregation, and coalescence) of the hexosomes was further examd. by the LUMiFuge technique. Two competing processes are presumed to take place during the formation of hexosomes: penetration of water from the continuous phase during dispersion, resulting in enhanced hydration of the head groups, and incorporation of the polymer chains into the hexosome structure while providing a stabilizing surface coating for the dispersed particles. Hydration is an essential stage in lyotropic liq. crystal (LLC) formation. The polymer, on the other hand, dehydrates the lipid heads, thereby introducing disorder into the LLC and reducing the domain size. Yet, a crit. min. polymer concn. is necessary in order to form stable nanosized hexosomes. These competing effects require the attention of those prepg. hexosomes. The competition between these two processes can be controlled. At relatively high polymer concns. (1-1.6 wt % of the total formulation of the soft particles), the hydration process seems to occur more rapidly than polymer adsorption. As a result, smaller and more stable soft particles with high symmetry were formed. On the other hand, when the polymer concn. is fixed at lower levels (\textless1.0 wt %), the homogenization process encourages only partial polymer adsorption during the dispersion process. This adsorption is insufficient; hence, max. hydration of the surfactant head group is reached prior to obtaining full adsorption, resulting in the formation of less ordered hexosomes of larger size and lower stability. [on SciFinder(R)]
Idit Amar-Yuli and Nissim. Garti. 2007. “Progress in structural transformation in lyotropic liquid crystals.” Colloids and Interface Science Series, 2, Colloid Stability, Part 2, Pp. 203–245. Abstract
A review. Polar lipids and certain surfactants are known to form thermodynamically stable lyotropic liq. crystals (LLC) when mixed with water. The major phases are lamellar (La), normal and reverse hexagonal (HI and HII) and cubic bicontinuous and discontinuous structures (VI VII and II, III, resp.). Theor., the transformation sequence of the phases with increasing water content is III → HII → VII → La → VI → HI → II. Lyotropic liq. crystal transformation was extensively studied and was found to take place also upon surfactant modifications (head or tail), addn. of a guest mol. (hydrophilic or hydrophobic), co-surfactant or electrolyte and varying the temp. The phases are of growing scientific and industrial interest because of their structural resemblance to human membranes through which drug passage of lipophilic compds. (vitamins, fats, oil and cholesterol) occurs and because of their high surface area and solubilization capacities. The variations in the phase formations, the phase behavior and phase transitions are of significant importance when designing a potential application for these systems. This chapter presents studies related to phase behavior and phase transitions as a function of different phys. and chem. conditions. The relationship between surfactant geometry that includes tail vol., tail length and area per head group and the corresponding phase formation is stressed. Research demonstrating dependence of the phase behavior on the addn. of a third component such as hydrophobic, hydrophilic guest mol. or co-surfactant is summarized. A brief overview of the instruments used in the above is also presented, illustrating their functionality in detecting the phase transitions and the unique information potentially extd. from each instrument. The main findings show successful control of lyotropic liq. crystal structure by altering the surfactant geometry in various respects: unsatn. site or degree, head or tail chain length and by an addnl. component such as linear or branched oils or alcs. [on SciFinder(R)]
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)]