Publications

2009
Shoshana Rozner, Popov, Inna , Uvarov, Vladimir , Aserin, Abraham , and Garti, Nissim. . 2009. Templated Cocrystallization Of Cholesterol And Phytosterols From Microemulsions.. Journal Of Crystal Growth, 311, 16, Pp. 4022–4033. doi:10.1016/j.jcrysgro.2009.06.027.
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)]
Nissim Garti, Amar-Yuli, Idit , Libster, Dima , and Aserin, Abraham. . 2009. Cubosomes As Delivery Vehicles.. In Highlights Colloid Sci., Pp. 279–290. New-York: Wiley-VCH Verlag GmbH & Co. KGaA. doi:10.1002/9783527623884.ch15.
A review on cubosomes, nanosoft particles that are formed when the liq. cryst. cubic phases are dispersed in aq. phase contg. a stabilizer (usually amphiphilic polymer), and their potential use as drug delivery vehicles. In the dispersed soft matter particles, the nanostructure of the original cubic inner structure remains intact despite the dispersion process. The three-dimensional symmetry of the cubic phases, combined with their large interfacial area and balanced content of hydrophobic and hydrophiic domains, make them very promising universal drug carriers, with numerous advantages over most other systems used at present. These exceptional phys. and chem. properties stimulated the study of the liq. crystal dispersions. Thus, one can take advantage of the complex phases for controlled delivery, while simultaneously having the benefit of the low viscosity of a system of soft nanoparticles dispersed in a continuous aq. phase. [on SciFinder(R)]
Rivka Efrat, Kesselman, Ellina , Aserin, Abraham , Garti, Nissim , and Danino, Dganit. . 2009. Solubilization Of Hydrophobic Guest Molecules In The Monoolein Discontinuous Ql Cubic Mesophase And Its Soft Nanoparticles.. Langmuir, 25, 3, Pp. 1316–1326. doi:10.1021/la8016084.
Hydrophobic bioactive guest mols. were solubilized in the discontinuous cubic mesophase (QL) of monoolein. Their effects on the mesophase structure and thermal behavior, and on the formation of soft nanoparticles upon dispersion of the bulk mesophase were studied. Four additives were analyzed. They were classified into two types based on their presumed location within the lipid bilayer and their influence on the phase behavior and structure. Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), polarized light microscopy, cryogenic-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS) were used for the anal. We found that carbamazepine and cholesterol (type I mols.) likely localize in the hydrophobic domains, but close to the hydrophobic-hydrophilic region. They induce strong perturbation to the mesophase packing by influencing both the order of the lipid acyl chains and interactions between lipid headgroups. This results in significant redn. of the phase transition enthalpy, and phase sepn. into lamellar and cubic mesophases above the max. loading capacity. The inclusion of type I mols. in the mesophase also prevents the formation of soft nanoparticles with long-range internal order upon dispersion. In their presence, only vesicles or sponge-like nanoparticles form. Phytosterols and coenzyme Q10 (type II mols.) present only moderate effects. These mols. reside in the hydrophobic domains, where they cannot alter the lipid curvature or transform the QL mesophase into another phase. Therefore, above max. loading, excess solubilizate ppts. in crystal forms. Moreover, when type II-loaded QL is dispersed, nanoparticles with long-range order and cubic symmetry (i.e., cubosomes) do form. A model for the growth of the ordered nanoparticles was developed from a series of intermediate structures identified by cryo-TEM. It proposes the development of the internal structure by fusion events between bilayer segments. [on SciFinder(R)]
Liron Bitan-Cherbakovsky, Yuli-Amar, Idit , Aserin, Abraham , and Garti, Nissim. . 2009. Structural Rearrangements And Interaction Within Hii Mesophase Induced By Cosolubilization Of Vitamin E And Ascorbic Acid.. Langmuir, 25, 22, Pp. 13106–13113. doi:10.1021/la901195t.
We investigated the effect of ascorbic acid (AA) cosolubilized with vitamin E (VE) on reverse hexagonal (HII) mesophase. The HII phase comprises monoolein (GMO)/D-$\alpha$-tocopherol (VE) in a ratio of 90/10 by wt. and 12.5 wt% water. The macrostructural characteristics of this system were detd. by polarized light microscopy and small-angle X-ray scattering measurements. We used differential scanning calorimetry and attenuated total reflectance Fourier transform IR to characterize the microstructure, the vibration of the functional groups, and the location of the AA guest mol. AA was incorporated to the system in two steps: 1-4 wt% AA and 5-6 wt% AA. We compared this system to one contg. tricaprylin as the oil phase, as previously reported. These measurements revealed that AA is localized first in the water rich-core and in the interface, and acts as a chaotropic mol. that decreases the water m.p. When a larger quantity of AA (5-6 wt%) is added, the system is satd., and the AA is located in the inner cylinder and manifested by more moderate distortion. The addn. of AA also causes alteration in the behavior of the GMO hydrocarbon chains and makes them more flexible. Further addn. of AA caused the GMO hydrocarbon chain to be more solvated by the VE hydrocarbon chain and enabled addnl. migration of VE; hence a decrease in the hydrophobic melting temp. occurred (similar to tricaprylin). Increasing the amt. of AA weakened the bonding between the GMO and water and created new bonds between AA and GMO and AA with water. [on SciFinder(R)]
R Lutz, Aserin, A, Wicker, L, and Garti, N. 2009. Structure And Physical Properties Of Pectins With Block-Wise Distribution Of Carboxylic Acid Groups.. Food Hydrocolloids, 23, 3, Pp. 786–794. doi:10.1016/j.foodhyd.2008.04.009.
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.
Y Kim, Lee, H, Jung, J, Rivner, J, Lutz, R, Arnold, R, Garti, N, and Wicker, L. 2009. Valencia Orange Pectinmethylesterases, Charge Modification Of Pectins, And Applications To Food Technology And Drug Delivery.. In Pectins Pectinases, Pp. 231–243. Wageningen Academic Publishers.
Fractionation of Valencia orange pulp prepns. resulted in PME active fractions contg. putative PMEs of 13, 27, and 36 kDa. NMR anal. indicated that pectin de-esterification by PMEs in these fractions resulted in block wise de-esterification of the substrate. Within the narrow frequency range of 0.57 to 0.76 for the dyad or 0.22-0.55 for the triad, little effect on G' value near 560 Pa is obsd. The relative contribution of total charge or distribution of charge cannot be clearly elucidated as the contribution of either depends on achieving a crit. limit of de-esterification. The position and shape of this crit. limit is influenced by the compn. of the dyads and triads of carboxylic acid groups. Applications of charge modified pectins include the ability to interact with proteins, stabilize emulsions for entrapment of addenda and for drug release. Under low pH, cationic milk proteins interact readily with pectins, esp. charge modified pectins. At pH 3.8, non fat dry milk, caseinates, $\alpha$S1,2, $\beta$- but not $ąppa$-casein pptd., esp. with modified pectin. Modified pectin apparently increased the soly. of sodium caseinate, suggesting a competition between protein-protein and protein-pectin interactions. Further, charge modified pectins reduced the surface tension and interfacial activity of dispersions and reduced the droplet size of emulsions. Finally, modified pectins showed superior entrapment and less release of indomethacin compared to com. low methoxyl pectins. [on SciFinder(R)]
2008
Shoshana Rozner, Aserin, Abraham , and Garti, Nissim. . 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. doi:10.1016/j.jcis.2008.01.055.
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)]
YD Livney. 2008. Complexes And Conjugates Of Biopolymers For Delivery Of Bioactive Ingredients Via Food.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 234–250. Woodhead Publishing Ltd. doi:10.1533/9781845694210.2.234.
A review discusses the aspects of complexes and conjugates of biopolymers related to the delivery of functional components via foods. The advantages of complexes and conjugates of proteins and polysaccharides used as building blocks for delivery systems are many. [on SciFinder(R)]
Anna Kogan, Popov, Inna , Uvarov, Vladimir , Cohen, Shmuel , Aserin, Abraham , and Garti, Nissim. . 2008. Crystallization Of Carbamazepine Pseudopolymorphs From Nonionic Microemulsions.. Langmuir, 24, 3, Pp. 722–733. doi:10.1021/la702763e.
Crystn. of carbamazepine (CBZ), an antiepileptic drug, pptd. from confined spaces of nonionic microemulsions was investigated. The study was aimed to correlate the structure of the microemulsion [water-in-oil (W/O), bicontinuous, and oil-in-water (O/W)] with the cryst. structure and morphol. of solid CBZ. The pptd. CBZ was studied by DSC, TGA, powder x-ray diffraction, single-crystal x-ray diffraction, SEM, and optical microscopy. The results suggest that the microstructure of the microemulsions influences the crystn. process and allows crystg. polymorphs that exhibit different crystal structure and habits. W/O nanodroplets orient the crystg. CBZ mols. to form a prism-like anhyd. polymorphic form with monoclinic unit cell and P21/n space group. Bicontinuous structures lead to platelike dihydrate crystals with orthorhombic unit cell and Cmca space group. The O/W nanodroplets cause the formation of needlelike dihydrate crystals with monoclinic unit cell and P21/c space group. The morphol. features of solid CBZ remain predetd. by the basic symmetry and parameters of its unit cell. Pptn. of CBZ pseudopolymorphs from supersatd. microemulsion is discussed in terms of oriented attachment that provides perfect packing of numerous sep. nucleated ordered nuclei of CBZ into microscale platelets and then into macroscopic crystals. Crystn. from microemulsion media enabling one to obtain the drug (CBZ) with predicted structure and morphol. should be of great significance for pharmaceutical applications. [on SciFinder(R)]
Hyoungill Lee, Rivner, Josh , Urbauer, Jeffrey L, Garti, Nissim , and Wicker, Louise. . 2008. De-Esterification Pattern Of Valencia Orange Pectinmethylesterases And Characterization Of Modified Pectins.. Journal Of The Science Of Food And Agriculture, 88, 12, Pp. 2102–2110. doi:10.1002/jsfa.3320.
Pectinmethylesterase (PME, E.C.1.1.11) isoenzymes from Valencia orange prepns. with different specific activities were used to de-esterify citrus and sugar beet pectins. Enzymic modification offers the opportunity to create pectins of tailored functionality and gelling ability. Based on NMR spectra, catalysis by all PME exts. produced block-wise de-esterification patterns in both citrus and sugar beet pectins. PME activity resulted in increased nos. of contiguous de-esterified groups and decreased nos. of contiguous esterified groups. De-esterification by PMEs increased the elastic property (G') of citrus and sugar beet pectins in the presence of calcium from 10 to 571 and from 0.05 to 201 Pa, resp. The results demonstrate the predilection of citrus PMEs toward block wise de-esterification of pectins and the relationship between calcium binding ability and de-esterification degree and patterning. Within a narrow range of de-esterification (37-48%) and with a narrow distribution of contiguous groups, PME modification did not markedly change gelling ability. At lower or higher de-esterification values, a 2-fold increase or 50-fold decrease, resp. in G' values was obsd. [on SciFinder(R)]
Rivka Efrat, Shalev, Deborah E, Hoffman, Roy E, Aserin, Abraham , and Garti, Nissim. . 2008. Effect Of Sodium Diclofenac Loads On Mesophase Components And Structure.. Langmuir, 24, 14, Pp. 7590–7595. doi:10.1021/la800603f.
We studied the effect of a model electrolytic drug on intermol. interactions, conformational changes, and phase transitions in structured discontinuous cubic QL lyotropic liq. crystals. These changes were due to competition with hydration of the lipid headgroups. Structural changes of the phase induced by solubilization loads of sodium diclofenac (Na-DFC) were investigated by directly observing the water, ethanol, and Na-DFC components of the resulting phases using 2H and 23Na NMR. Na-DFC interacted with the surfactant glycerol monoolein (GMO) at the interface while interfering with the mesophase curvature and also competed with hydration of the surfactant headgroups. Increasing quantities of solubilized Na-DFC promoted phase transitions from cubic phase (discontinuous (QL) and bicontinuous (Q)) into lamellar structures and subsequently into a disordered lamellar phase. Quadrupolar coupling of deuterated ethanol by 2H NMR showed that it is located near the headgroups of the lipid and apparently is hydrogen bonded to the GMO headgroups. A phase transition between two lamellar phases (L$\alpha$ to L$\alpha$*) was seen by 23Na NMR of Na-DFC at a concn. where the characteristics of the drug change from kosmotropic to chaotropic. These findings show that loads of solubilized drug may affect the structure of its vehicle and, as a result, its transport across skin-blood barriers. The structural changes of the mesophase may also aid controlled drug delivery. [on SciFinder(R)]
LA Shaw, Faraji, H, Aoki, T, Djordjevic, D, McClements, DJ , and Decker, EA . 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. doi:10.1533/9781845694210.2.184.
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)]
CM Sabliov and Astete, CE. 2008. Encapsulation And Controlled Release Of Antioxidants And Vitamins.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 297–330. Woodhead Publishing Ltd. doi:10.1533/9781845694210.3.297.
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)]
K Kailasapathy. 2008. Encapsulation And Controlled Release Of Folic Acid.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 331–343. Woodhead Publishing Ltd. doi:10.1533/9781845694210.3.331.
A review discusses the delivery of microencapsulated folates through food such as cheese and its controlled release. [on SciFinder(R)]
A Millqvist-Fureby. 2008. Encapsulation Approaches For Proteins.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 404–425. Woodhead Publishing Ltd. doi:10.1533/9781845694210.3.404.
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)]
S.-J. Lee and Ying, DY. 2008. Encapsulation Of Fish Oils.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 370–403. Woodhead Publishing Ltd. doi:10.1533/9781845694210.3.370.
A review describes the microencapsulation technologies and encapsulant materials used to deliver fish oils and the application of encapsulated fish oils in food products. It also discusses the benefits of fish oil and challenges of adding fish oils to foods. [on SciFinder(R)]
CP Champagne and Kailasapathy, K. 2008. Encapsulation Of Probiotics.. In Delivery Controlled Release Bioact. Foods Nutraceuticals, Pp. 344–369. Woodhead Publishing Ltd. doi:10.1533/9781845694210.3.344.
A review discusses the encapsulation technologies for probiotics. However, technologies applied to probiotics are generally limited to gel particles, spray-coating, spray-drying, extrusion and emulsions. [on SciFinder(R)]
Marina Shevachman, Garti, Nissim , Shani, Arnon , and Sintov, Amnon C. 2008. Enhanced Percutaneous Permeability Of Diclofenac Using A New U-Type Dilutable Microemulsion.. Drug Development And Industrial Pharmacy, 34, 4, Pp. 403–412. doi:10.1080/03639040701662479.
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)]
M Subirade and Chen, L. 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. doi:10.1533/9781845694210.2.251.
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)]

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