Nissim Garti

Institute of Chemistry
Faculty of Science
The Hebrew University, Jerusalem 91904, Israel
Tel: +972-2-6586574; Fax: +972-2-6520262
E-mail:garti@vms.huji.ac.il
Website: http://nissim-garti.co.il/

Novel micellar cubic nanostructures and the corresponding micellosomes for improved solubilization and delivery of bioactives

We have recently developed a new set of novel nanostructures that are different from our first, second and third generation of "nano swollen micellar self-assembled liquid vehicles" (NSSL) that are already presently in the market place and used in the food and cosmetic industry (Figure 1).

Figure 1: Novel nanostructured self-assembled liquid vehicles (NSSL)

We have recently discovered novel self-assembled nano structures derived from lyotropic liquid crystals. The novel phases (compositions) are transparent 'crystal clear' slightly viscous (but pourable) liquids composed of "reverse micelles organized in a cubic symmetry". We termed the new structures "liquid cubic discontinuous structures" or "QL phases" (Figure 2). These structures can be further dispersed in aqueous phase and stabilizers to form what we called "micellosomes" or "dispersed soft-matter structures". These unique structures are novel delivery vehicles for bioactive ingredients for food, cosmetic and pharmaceutical applications. The novel structures advantages are in their low cost, easy to make and easy to use for various delivery applications such as oral intake, topical applications (dermal and transdermal), nasal, sprays, intravenous, etc. The mesostructures can be formulated into liquid preparations, beverages, softgels, capsules, topical gels, injectable fluids, spray fluids, etc. The nanostructures (domains of 10-30 nm) have very high solubilization (entrapment) capacities) of insoluble and soluble active matter including polymeric actives addenda. The QL and the corresponding micellosomes are stable thermodynamically and have very long shelf-life. The formulations are based on amphiphilic lipids, fats and other co-stabilizers carefully selected from a permitted list of ingredients for food, cosmetic or pharmaceutical applications. The bioavailability and transfer across membranes is significantly better (10 fold or more depending on the structure of the bioacative compound) than any other formulations that exist presently in the market place. We have solubilized, in a molecular form, active ingredients such as lycopene, lutein, phytosterols, CoQ10, tocopherols and drugs such as carbamazepine, diclofenac, celecoxib and others. Synergistic solubilization of blends of various bioactives was observed and studied. The novel structures have maximum skin penetration capabilities with minimum irritation effects. The project is a joint effort of physical and colloid chemists (Garti and Aserin), physicists and experts in structural analysis using advance analytical tools such as SAXS, SANS, Cryo-TEM, SD-NMR, ESR, TDS) (Danino, Regev, Kaler, Wachtel, Hoffman, Ottaviani) and medical experts on skin transport and properties (Milner, Sintov) and oral application (Rotshtein, Tel-Ashomer Hospital). The group collaborates with groups of Scientists in Columbia University, Stony Brook University (Rafailovich, Rigas) and Stony Brook Hospital in NY (Nachman, Rigas). The commercial value is very obvious since these new nanostructures can provide a solution to pharmaceutical, cosmetic and food companies that struggle with new non-soluble and poorly-bioavailability drugs and for those that are searching for more suitable delivery systems for existing bioactives. The novel technology is of special interest to those that would like to deliver active matter in a nano liquid form transversally. This is an excellent solution for local targeted delivery of active matter of anti-inflammatory, anticancer and other drugs that must be delivered in a liquid (spray form) to sensitive or specific areas of the treatments.

Figure 2: Schematic illustration of the cubic nano-sized discontinuous Q_L structure

Specific research topics related to Nanoscience and Nanotechnology:

• Liquid nano-vehicles based on microemulsions and emulsified microemulsions.
• Novel nanosized self-assembled liquid vehicles (NSSL technology).
• Lyotropic liquid crystals (QL and micellosomes) as solubilization vehicles for non-soluble bioactives.
• Transdermal and transmembrane competitive transport via nano-carriers.
• Nutraceuticals and food supplements- structure, mechanisms and improvement of the bioavailability.
• Regioselectivity and interfacial enzymatic reactions.
• Development of new and advanced analytical tools for studying structural aspects of nanosized systems such as SAXS, SD-NMR, Cryo-TEM, Dielectric Spectroscopy, DSC, rheology, EPR, NMR-chromatography.

List of publications in Nanoscience and Nanotechnology (2010-2011)

• Janna Gurfinkel, Abraham Aserin, Nissim Garti. "Interactions of surfactants in nonionic/anionic reverse hexagonal mesophases and solubilization of ?-chymotrypsinogen A". Colloids and Surfaces A: Physicochemical and Engineering Aspects, 392(1), 322-328, (2011).
• Amar-Yuli, Idit; Azulay, Doron; Mishraki, Tehila; Aserin, Abraham; Garti, Nissim. "The role of glycerol and phosphatidylcholine in solubilizing and enhancing insulin stability in reverse hexagonal mesophases". Journal of Colloid and Interface Science, 364(2), 379-387. (2011)
• Bitan-Cherbakovsky, Liron; Libster, Dima; Aserin, Abraham; Garti, Nissim. "Complex Dendrimer-Lyotropic Liquid Crystalline Systems: Structural Behavior and Interactions". Journal of Physical Chemistry B, 115(42), 11984-11992, (2011).
• Deutch-Kolevzon, Rivka; Aserin, Abraham; Garti, Nissim. "Synergistic cosolubilization of omega-3 fatty acid esters and CoQ10 in dilutable microemulsions". Chemistry and Physics of Lipids, 164(7), 654-663,(2011).
• Amar-Yuli, Idit; Adamcik, Jozef; Blau, Shoshana; Aserin, Abraham; Garti, Nissim; Mezzenga, Raffaele." Controlled embedment and release of DNA from lipidic reverse columnar hexagonal mesophases". Soft Matter, 7(18), 8162-8168, (2011).
• Cohen-Avrahami, Marganit; Libster, Dima; Aserin, Abraham; Garti, Nissim. "Sodium Diclofenac and Cell-Penetrating Peptides Embedded in HII Mesophases: Physical Characterization and Delivery". Journal of Physical Chemistry B, 115(34), 10189-10197, (2011).
• Mishraki, Tehila; Ottaviani, Maria Francesca; Shames, Alexander I.; Aserin, Abraham; Garti, Nissim. "Structural Effects of Insulin-Loading into HII Mesophases Monitored by Electron Paramagnetic Resonance (EPR), Small Angle X-ray Spectroscopy (SAXS), and Attenuated Total Reflection Fourier Transform Spectroscopy (ATR-FTIR)". Journal of Physical Chemistry B, 115(25), 8054-8062, (2011).
• Amar-Zrihen, Natali; Aserin, Abraham; Garti, Nissim. "Food volatile compounds facilitating HII mesophase formation: Solubilization and stability". Journal of Agricultural and Food Chemistry, 59(10), 5554-5564, (2011).
• Libster, Dima; Aserin, Abraham; Garti, Nissim. "Interactions of biomacromolecules with reverse hexagonal liquid crystals: Drug delivery and crystallization. Applications". Journal of Colloid and Interface Science, 356(2), 375-386, (2011).
• Pemberton, Chava; Hoffman, Roy E.; Aserin, Abraham; Garti, Nissim."NMR Chromatography Using Microemulsion Systems". Langmuir ,27(8), 4497-4504,(2011).
• Mourelatou, Elena A.; Libster, Dima; Nir, Ido; Hatziantoniou, Sophia; Aserin, Abraham; Garti, Nissim; Demetzos, Costas. "Type and Location of Interaction between Hyperbranched Polymers and Liposomes. Relevance to Design of a Potentially Advanced Drug Delivery Nanosystem (aDDnS)". Journal of Physical Chemistry B, 115(13), 3400-3408, (2011).
• Pemberton, Chava; Hoffman, Roy; Aserin, Abraham; Garti, Nissim. "New insights into silica-based NMR "chromatography"". Journal of Magnetic Resonance, 208(2), 262-269, (2011).
• Achrai, Ben; Libster, Dima; Aserin, Abraham; Garti, Nissim. "Solubilization of Gabapentin into HII Mesophases". Journal of Physical Chemistry B, 115(5), 825-835, (2011).
• Libster, Dima; Aserin, Abraham; Amar-Yuli, Idit; Mishraki, Tehila; Domovich-Eisenberg, Yael; Livnah, Oded; Garti, Nissim." Crystallization of cyclosporin A in lyotropic reverse hexagonal liquid crystals". CrystEngComm (2010), 12(7), 2034-2036.
• Nir, Ido; Aserin, Abraham; Libster, Dima; Garti, Nissim. Solubilization of a Dendrimer into a Microemulsion. Journal of Physical Chemistry B ,114(50), 16723-16730,(2010),
• Amsalem, Orit; Aserin, Abraham; Garti, Nissim. Phospholipids-embedded fully dilutable liquid nanostructures. Part 2: The role of sodium diclofenac. Colloids and Surfaces, B: Biointerfaces ,81(2), 422-429(2010),.
• Ishai, Paul Ben; Libster, Dima; Aserin, Abraham; Garti, Nissim; Feldman, Yuri. Influence of Cyclosporine A on Molecular Interactions in Lyotropic Reverse Hexagonal Liquid Crystals. Journal of Physical Chemistry B (2010), 114(40), 12785-12791.
• Efrat, Rivka; Abramov, Zoya; Aserin, Abraham; Garti, Nissim. Nonionic-Anionic Mixed Surfactants Cubic Mesophases. Part I: Structural Chaotropic and Kosmotropic Effect. Journal of Physical Chemistry B (2010), 114(33), 10709-10716.
• Klein, Miri; Aserin, Abraham; Ben Ishai, Paul; Garti, Nissim. Interactions between whey protein isolate and gum Arabic. Colloids and Surfaces, B: Biointerfaces (2010), 79(2), 377-383.
• Yariv, Doron; Efrat, Rivka; Libster, Dima; Aserin, Abraham; Garti, Nissim. In vitro permeation of diclofenac salts from lyotropic liquid crystalline systems. Colloids and Surfaces, B: Biointerfaces (2010), 78(2), 185-192.
• Cohen-Avrahami, Marganit; Aserin, Abraham; Garti, Nissim. HII mesophase and peptide cell-penetrating enhancers for improved transdermal delivery of sodium diclofenac. Colloids and Surfaces, B: Biointerfaces (2010), 77(2), 131-138.
• Klein, Miri; Aserin, Abraham; Svitov, Inna; Garti, Nissim. Enhanced stabilization of cloudy emulsions with gum Arabic and whey protein isolate. Colloids and Surfaces, B: Biointerfaces (2010), 77(1), 75-81.
• Rozner, Shoshana; Shalev, Deborah E.; Shames, Alexander I.; Ottaviani, Maria Francesca; Aserin, Abraham; Garti, Nissim. Do food microemulsions and dietary mixed micelles interact? Colloids and Surfaces, B: Biointerfaces (2010), 77(1), 22-30.
• Mishraki, Tehila; Libster, Dima; Aserin, Abraham; Garti, Nissim. Temperature-dependent behavior of lysozyme within the reverse hexagonal mesophases (HII). Colloids and Surfaces, B: Biointerfaces (2010), 75(2), 391-397.
• Mishraki, Tehila; Libster, Dima; Aserin, Abraham; Garti, Nissim. Lysozyme entrapped within reverse hexagonal mesophases: Physical properties and structural behavior. Colloids and Surfaces, B: Biointerfaces (2010), 75(1), 47-56.
• Bitan-Cherbakovsky, Liron; Yuli-Amar, Idit; Aserin, Abraham; Garti, Nissim. Solubilization of Vitamin E into HII LLC Mesophase in the Presence and in the Absence of Vitamin C. Langmuir (2010), 26(5), 3648-3653.
• Ben Ishai Paul; Libster Dima; Aserin Abraham; Garti Nissim; Feldman Yuri. Influence of cyclosporine A on molecular interactions in lyotropic reverse hexagonal liquid crystals. The Journal of Physical Chemistry B (2010), 114(40), 12785-12791.

Five most significant publications in the last five years:

• Kogan Anna; Garti Nissim. Microemulsions as transdermal drug delivery vehicles. Advances in Colloid and Interface Science, (2006), 123: 369-385. Times Cited: 121.
• Garti Nissim. Double emulsions - Scope, limitations and new achievements. Colloids and Surfaces A, (1997), 123, 233-246. Times Cited: 95.
• Garti N.; Yaghmur A.; Leser M.E.; Clement, V.; Watzke, H.J. Improved oil solubilization in oil/water food grade microemulsions in the presence of polyols and ethanol. Journal of Agricultural and Food Chemistry, (2001), 49(5), 2552-2562. Times Cited: 92.
• Feldman Y.; Kozlovich N.; Nir I.; Garti, N.; Archipov, V.; Idiyatullin, Z.; Zuev, Y.; Fedotov, V. Mechanism of transport of charge carriers in the sodium bis(2-ethylhexyl) sulfosuccinate-water-decane microemulsion near the percolation temperature threshold. Journal of Physical Chemistry B, (1996), 100(9), 3745-3748. Times Cited: 91.
• Regev O; Ezrahi S; Aserin A; Garti, N.; Wachtel, E.; Kaler, E.W.; Khan, A.; Talmon, Y. A study of the microstructure of a four-component nonionic microemulsion by cryo-TEM, NMR, SAXS, and SANS. Langmuir, (1996), 12(3), 668-674. Times Cited: 77.

New patents and patents utilization (2009-2011):

• Garti, Nissim; Aserin, Abraham; Libster, Dima; Mishraki, Tehila; Amar-Yuli, Idit; Bitan-Chervkovsky, Liron. Reverse hexagonal mesophase liquid crystals and uses thereof. PCT Int. Appl. (2010), WO 2010150262 A2 20101229.
• Hoffman, Roy; Garti, Nissim; Aserin, Abraham; Pemberton, Chava. Liquid compositions and uses thereof for generating diffusion ordered NMR spectra of mixtures. PCT Int. Appl. (2010), WO 2010023673 A1 20100304.

Cooperation with other universities in Israel:

• Prof. Y. Feldman, Department of Applied Physics.
• Dr. D. E. Shalev, Wolfson Centre for Applied Structural Biology.
• Dr. P. Ben Ishai Department of Applied Physics.
• Prof. O. Livnah, Department of Biological Chemistry.
• Prof. G. Shoham, Department of Inorganic Chemistry and the Laboratory for Structural Chemistry and Biology.
• Dr. Y. Domovich-Eisenberg, Department of Biological Chemistry.
• Dr. R. E. Hoffman, NMR Laboratory, The Institute of Chemistry.
• Dr. I. Popov, The Unit for Nanoscopic Characterization, The Center for Nanoscience and Nanotechnology.
• Dr. V. Uvarov, The Unit for Nanoscopic Characterization, The Center for Nanoscience and Nanotechnology.
• Dr. S. Cohen, Department of Inorganic and Analytical Chemistry, The Institute of Chemistry.

With other universities:

• Prof. A. I. Shames, - Department of Physics, Ben-Gurion University of the Negev.
• Prof. C. Demetzos, School of Pharmacy, Department of Pharmaceutical Technology, Panepistimioupolis, University of Athens, Zografou, Athens, Greece.
• Dr. E. A. Mourelatou, School of Pharmacy, Department of Pharmaceutical Technology, Panepistimioupolis, University of Athens, Zografou, Athens, Greece.
• Dr. S. Hatziantoniou, School of Pharmacy, Department of Pharmaceutical Technology, Panepistimioupolis, University of Athens, Zografou, Athens, Greece.
• Prof. A. C. Sintov, Department of Biomedical Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
• Prof. D. Danino, Department of Biotechnology and Food Engineering, and Russell Berrie Nanotechnology Institute, Technion ? Israel Institute of Technology, Haifa, Israel.
• Prof. R. Mezzenga, ETH Zurich, Food & Soft Materials Science, Institute of Food, Nutrition & Health, Zurich, Switzerland.
• Dr. J. Adamcik, ETH Zurich, Food & Soft Materials Science, Institute of Food, Nutrition & Health, Zurich, Switzerland.
• Prof. M. F. Ottaviani,- Department of Geological Sciences, Chemical and Environmental Technologies, University of Urbino, Loc. Crocicchia, Urbino 61029, Italy.
• Prof. O. Regev, Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.
• Prof. I. Nir, Department of Physical Chemistry, Israel Institute for Biological Research, Ness Ziona, Israel.
• Dr. E. Wachtel, Weizmann Institute of Sciences, Department of Materials & Interfaces, Rehovot, Israel.

Distinctions and awards:

• 2011, Recipient of the AOCS Corporate Achievement Award for NutraLease Ltd.
• 2010, Nominated as the Ratner Family Chair of Chemistry.
• 2009, French Government Special Award for Foreign Scientist on Unique Achievements.
• 2009, The Israel Food Industry Society Award- Lifetime Achievement Award for Outstanding Contribution to the Food in Israel. Awarded during the "Food in the New Era" conference. June 28, Airport City, Israel.
• 2009, The Chung Award of the American Oil Chemist's Society for the Lifetime Achievement in Lipid Research. The only Israeli scientist to receive the award during the 100 years of the Society. May, Orlando, FL, USA.
• 2008, The Israeli President Award - One of the 60 Most Innovative Future Technologies of Israel (NutraLease Ltd.), "Facing Tomorrow" - The Israeli Presidential Conference, Jerusalem, May 13-15, (awarded in the presence of the American President - George W. Bush).
• 2007, International Food Technology (IFT) Annual Award for the Food Expo Innovation Award granted to Prof. Garti from NutraLease Ltd./Adumim Food Ingredients/P.L. Thomas for their NutraLease Nanoencapsulation Technology, Chicago, IL, USA.
• 2007, The Tnuva Institute Award granted to Prof. Garti for its outstanding research activities on lyotropic liquid crystals as delivery vehicles, Tel Aviv, January.

Students, postdocs and researchers (include those graduated in 2010-2011):

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