All Publications

Dima Libster, Aserin, Abraham , and Garti, Nissim. . 2012. Topical Delivery Of Pharmaceuticals Using Liquid Crystalline Structures.. In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 151–186. USA: DEStech Publications, Inc.
A review. Transdermal delivery has lately emerged as a valuable alternative method to improve bioavailability and increase pharmaceutical efficacy of various drugs. Transdermal administration can potentially minimize side effects as well as first-pass metab. It has been used successfully for hormone replacement therapy, smoking cessation, and pain management. However, there have been challenges in the expanding use of the technol. to numerous types of pharmaceuticals, including extremely hydrophilic or lipophilic drugs, peptides, proteins, and other macromols. In this context, colloidal drug carriers, and in particular lyotropic liq. crystals (LLCs), seem to be promising candidates as the vehicles of unconventional delivery for various drugs. Such vehicles can provide enhanced drug soly., relative protection of the solubilized drugs, and controlled release of drugs, while avoiding substantial side effects. Exhibiting interesting properties for a topical delivery system, LLCs were considered and have been studied as delivery vehicles of pharmaceuticals via the skin and mucosa. This review focuses on lyotropic non-lamellar lyotropic mesophases (hexagonal and cubic) and their nano-dispersions as topical delivery vehicles. Recent advances in transdermal and mucosal drug delivery via LLC carriers are demonstrated and discussed. [on SciFinder(R)]
Vesselin Kolev, Ivanova, Anela , Madjarova, Galia , Aserin, Abraham , and Garti, Nissim. . 2012. Molecular Dynamics Approach To Water Structure Of Hii Mesophase Of Monoolein.. Journal Of Chemical Physics, 136, 7, Pp. 074509/1–074509/11. doi:10.1063/1.3685509.
The goal of the present work is to study theor. the structure of water inside the water cylinder of the inverse hexagonal mesophase (HII) of glyceryl monooleate (monoolein, GMO), using the method of mol. dynamics. To simplify the computational model, a fixed structure of the GMO tube is maintained. The nonstd. cylindrical geometry of the system required the development and application of a novel method for obtaining the starting distribution of water mols. A predictor-corrector schema is employed for generation of the initial d. of water. Mol. dynamics calcns. are performed at const. vol. and temp. (NVT ensemble) with 1-dimensional periodic boundary conditions applied. During the simulations the lipid structure is kept fixed, while the dynamics of water is unrestrained. Distribution of hydrogen bonds and d. as well as radial distribution of water mols. across the water cylinder show water structure deep in the cylinder (∼6 \AA below the GMO heads). The obtained results may help understanding the role of water structure in the processes of insertion of external mols. inside the GMO/water system. The present work has a semi-quant. character and it should be considered as the initial stage of more comprehensive future theor. studies. (c) 2012 American Institute of Physics. [on SciFinder(R)]
Vesselin Kolev, Aserin, Abraham , and Garti, Nissim. . 2012. Dividing Planes Of Hexagonal Hii Mesophase.. In Self-Assem. Supramol. Archit., Pp. 79–96. John Wiley & Sons, Inc. doi:10.1002/9781118336632.ch3.
A review. Presented is a brief review of the cylindrical dividing surfaces (planes) of the hexagonal inverse HII phase-Luzzati, pivotal, and neutral. They are presented as interrelated surfaces through the general expression of elastic energy per mol. valid for the corresponding surface. For each of the planes, the routine for deriving the plane parameters-radius, area, and vol. per mol., as well as their role in terms of mech. description the of HII phase-is described in detail. Special attention is paid to the numerical routines for parameter calcns. from exptl. data, using least-squares routines and the related methods of merit function optimization (minimization). In addn., cases of error estn. are presented along with discussions about the accuracy of used numerical routines. [on SciFinder(R)]
Chandrashekhar V Kulkarni and Glatter, Otto. . 2012. Hierarchically Organized Systems Based On Liquid Crystalline Phases.. In Self-Assem. Supramol. Archit., Pp. 157–191. John Wiley & Sons, Inc. doi:10.1002/9781118336632.ch6.
A review. Presented are hierarchically organized nanostructures formed from lyotropic liq. cryst. (LC) phases. The nano-, micro-, and macroscopic structural hierarchy arises from the kinetic stability of various lyotropic phases dispersed in oil-in-water (O/W) or water-in-oil (W/O) emulsions. When an O/W emulsion consists of a dispersion of LC nanoparticles stabilized by certain stabilizers, it is called an ISAsome, i.e., an internally self-assembled particle. In contrast, when the water droplets are dispersed in a continuous film of LC nanostructures, they are called W/O-nanostructured emulsions, which do not require a stabilizing agent. Both emulsions exhibit fascinating properties that can be tuned to a great extent. Such tunability proliferates their performance in various applications. Herein, the formation, multiscale structure, properties, and their modulation for the aforementioned superstructures formed from LC phases are discussed. Focusing further on ISAsomes Pickering emulsions stabilized by various nanoparticles are presented, including synthetic clay laponite and silica nanoparticles. The transfer of hydrophobic components among several differently nanostructured ISAsomes was studied by time-resolved x-ray scattering; the effects of Isasome-forming components are also illustrated. The continuous aq. region of ISAsome dispersions can be loaded with water-sol. polymers that form thermo-reversible hydrogels. This enables the entrapment of ISAsome systems into such hydrogel networks. Subsequent drying of these loaded systems facilitates immobilization of ISAsomes, which can be easily restored by rehydration of the loaded dry films. The formation of hydrogels in the aq. reservoirs of W/O-nanostructured emulsions also proved advantageous in terms of tuning their viscosity and, in some cases, enhancing their stability. The current contribution covers systems with diverse structural hierarchy, ranging from equil. liq. cryst. nanostructures to the systems with multiple orders of length scales in their structure. [on SciFinder(R)]
Dima Libster, Aserin, Abraham , and Garti, Nissim. . 2012. Recent Developments In Lyotropic Liquid Crystals As Drug Delivery Vehicles.. In Self-Assem. Supramol. Archit., Pp. 219–256. John Wiley & Sons, Inc. doi:10.1002/9781118336632.ch8.
A review. Recently, self-assembled lyotropic liq. crystals (LLCs) of lipids and water have attracted the attention of both the scientific and the applied research communities due to the remarkable structural complexity and practical potential of these nanostructures in diverse applications. The phase behavior of mixts. of glycerol monooleate (monoolein, GMO) was particularly well studied due to the potential utilization of these systems in drug delivery systems, food products, and encapsulation and crystn. of proteins. The present chapter summarizes structural features of LLCs and recent systematic efforts to utilize these for solubilization and the potential release of drugs and biomacromols. One of the most interesting applications is the implementation of cell-penetrating peptides in the reversed hexagonal mesophase to enhance the skin-penetrating pattern of a model drug (sodium diclofenac). Liq. crystal vehicles were shown to allow "on demand" targeted release, based on controlling the polymorphism of lyotropic liq. cryst. mesophases. Novel liq. cryst. matrix-gold nanorod hybrid materials were reported to induce light-triggered phase transition of liq. cryst. phases. Hydrophobized gold nanorods (GNRs) have been incorporated within the LLCs, composed of phytantriol and water, to provide remote heating, and trigger the phase transitions on irradn. at close to their resonant wavelength. A new pathway to pH-responsive LLCs, enabling the controlled release of hydrophilic drugs diffusing through the water channels of the mesophases, was also investigated. The system is capable of self-assembling into a reverse bicontinuous cubic phase of Im3m symmetry at pH 7 and transforming into a reverse columnar hexagonal phase at pH 2. Lyotropic liq. crystals were shown to entrap several nucleotides into cubic and lamellar monoolein-based mesophases in order to protect them and enable their release. DNA (DNA) within two types of reverse columnar hexagonal mesophases was studied, one based on pure nonionic lipids and the other decorated by cationic lipids to induce opposite charges at the surfaces of the water channels of the mesophases. This provided new opportunities in the design technologies for DNA transfection and for gene delivery. The main outcomes of the described research demonstrated that control of the phys. properties of hexagonal LLC on different length scales is key for rational design of these systems as delivery vehicles for both low-mol.-wt. therapeutics and biomacromols. [on SciFinder(R)]
Raffaele. Mezzenga. 2012. Physics Of Self-Assembly Of Lyotropic Liquid Crystals.. In Self-Assem. Supramol. Archit., Pp. 1–20. John Wiley & Sons, Inc. doi:10.1002/9781118336632.ch1.
A review. Reviewed are recent advances in the understanding of self-assembly principles in lipid-based lyotropic lipid crystals, from the original rationalization achieved using the crit. packing parameter up to recent, more sophisticated thermodn. approaches, such as the SCF theory, which can be efficiently used to minimize the total free energy of a lipid-water system and identify stable mesophases. Highlighted is the importance of reversible hydrogen bonding as one of the key parameters ruling the self-assembly in these systems and examine the implications this may have also in real applications. The current understanding on the dynamics of phase transitions are finally discussed and the status of the art on current atomistic approaches to investigate the relaxation dynamics in these systems is reviewed. [on SciFinder(R)]
N Perkas, Gedanken, A, Perelshtein, I, and Shimanovich, U. 2012. Embedding Antibacterial Inorganic Nanoparticles And Proteinaceous Microspheres In Textiles By A Sonochemical Method.. In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 341–366. DEStech Publications, Inc.
A review. A review on the works that have been done on the antibacterial functionalization of textiles using a sonochem. method. It covers the works published until Dec. 2009 by different authors using ultrasound irradn. [on SciFinder(R)]
Shifra Rokach, Ottaviani, Maria Francesca , Shames, Alexander I, Nir, Ido , Aserin, Abraham , and Garti, Nissim. . 2012. W/O Microemulsions As Dendrimer Nanocarriers: An Epr Study.. Journal Of Physical Chemistry B, 116, 41, Pp. 12633–12640. doi:10.1021/jp307616b.
A complex system, based on a dendrimer solubilized in the aq. core of water-in-oil microemulsion, may combine the advantages of both dendrimers and microemulsions to provide better control of drug release. We report for the first time the use of EPR technique to det. the effect of solubilized dendrimer on the structure of the microemulsion. The solubilized poly(propyleneimine) (PPI-G2) interacts with sodium bis(2-ethylhexyl) sulfosuccinate (AOT). EPR anal. provided information on polarity, microviscosity, and mol. order of the systems. Polarity and microviscosity increased from unloaded water-in-oil microemulsion to the system loaded with 0.2 wt. % PPI-G2, but remained unchanged with higher PPI-G2 loads. The degree of order also increased with 0.2 wt. % PPI-G2 with only minor addnl. increase with larger quantities (25 wt. %) of PPI-G2. Variations in pH only slightly affected the structure of microemulsion in the absence and presence of the loaded dendrimers. Aliph. oils with longer lipophilic chains enhanced the structural order of the microemulsion. On increasing water content, polarity and degree of order increased. PPI-G2 dendrimer in small loads is attracted by the neg. charged AOT and thus intercalates in the interface of the droplets. Yet, at higher PPI-G2 loads, the excess mols. are solubilized in the water core. [on SciFinder(R)]
Alejandro D Rey and Herrera-Valencia, EE. 2012. Rheological Theory And Simulation Of Surfactant Nematic Liquid Crystals.. In Self-Assem. Supramol. Archit., Pp. 21–77. John Wiley & Sons, Inc. doi:10.1002/9781118336632.ch2.
Presented a comprehensive review of rheol. theory, modeling, and simulation of surfactant nematic liq. cryst. phases, including calamitic and discotic micellar solns. and wormlike micelles. A review of verifiable rheol. liq. crystal models for lyotropic nematics highlighting the mechanisms that control orientation behavior under shear, anisotropic viscoelasticity, and non-Newtonian behavior. Since defects and textures are essential characteristics of these materials that affect the flow properties, an in-depth review of phys. and rheophys. defects is presented, including defect nucleation and coarsening processes. The theory for micellar nematics is applied to textures, flow birefringence, phase transition under shear, orientation fluctuations, and flow alignment, and the predictions are compared with exptl. data. The theory is finally applied to transient shear flows of wormlike micellar nematic solns., and the predicted banded textures and transient stress responses are compared to rheol. expts. The predictions provide a new way to ext. addnl. information from exptl. rheol. data and allow to distinguish the role of liq. cryst. properties such as viscoelastic anisotropy, flow alignment, coupling between orientation kinematics, and flow kinematics. The rheol. predictions show a strong similarity with other nematic materials, including low-molar-mass thermotropes and lyotropic nematic polymers. [on SciFinder(R)]
Perla Relkin and Anton, Marc. . 2012. Protein- And Lipid-Based Nano- And Mirco-Capsules, As Food Micronutrient Carriers.. In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 125–149. DEStech Publications, Inc.
A review. Com. available food ingredients, such as proteins, satd. or polyunsatd. lipids and polysaccharides have nutritional and structure-forming properties at different scale levels. They belong to classes of biodegradable and biocompatible biomaterials which are the focus of intensive research studies thanks to their potentiality to be used as bioactive matrix carriers. This chapter will be concerned with physicochem. and structural properties of protein and lipoprotein assemblies naturally present in food or induced by thermomech. treatments; and with the description of exptl. design and formulation of nutrient-rich products. In the first part, we will focus on the structural properties, from nano- to microsize level, of casein micelle heat-induced proteins aggregates, and of natural egg lipoproteins in relation to their property of protecting nutrients or bioactive compds. (vitamins, unsatd. fatty acids, antioxidants, aroma compds.) and stabilizing emulsions. In the second part we will draw attention to the relation between their protective and carrying properties with the structure and dynamics, at different scales, of such complex food matrixes. In conclusion, the trends in research concerning the delivery of nutrients in complex food will be debated. [on SciFinder(R)]
Anan Yaghmur and Rappolt, Michael. . 2012. Recent Advances In The Characterization Of Lipid-Based Nanocarriers.. In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 187–208. DEStech Publications, Inc.
A review. Soft self-assembled lipidic systems with well-defined nanostructures have become increasingly important in the development of pharmaceutical, food, and cosmetic delivery systems. They have key roles in overcoming the insufficiency of bioavailability and other obstacles in drug delivery systems, such as severe side effects and the toxicity of poorly water-sol. bioactive mols. In particular, self-assembled nanostructures of naturally occurring surfactant-like lipids represent an interesting family of nanocarriers. This family of biodegradable and biocompatible materials displays structures closely related to those obsd. in biol. membranes and enables the formation of efficient delivery systems. The optimal utilization of these nanostructured objects requires a full understanding of their physicochem. properties and detailed characterization of their structures. Their stability after administration is a key issue in the development of excipients with a good performance and a significant redn. of unwanted side effects. This chapter summarizes recent studies of the possibility of utilizing soft lipidic self-assembled systems as drug and food nanocarriers. The scope covers recent investigations that have attempted to shed light on the formation of delivery systems based on microemulsions, and different nanostructured aq. dispersions. It highlights also some recent advances in the characterization of these complex soft nanoobjects. The main focus is placed on the recent developments in the field of small-angle scattering methods, dynamic light scattering (DLS), electron microscopy (tilt-angle cryo-TEM, and cryo-FESEM), and NMR (NMR) techniques. [on SciFinder(R)]
Anan Yaghmur and Glatter, Otto. . 2012. Self-Assembly In Lipidic Particles.. In Self-Assem. Supramol. Archit., Pp. 129–155. John Wiley & Sons, Inc. doi:10.1002/9781118336632.ch5.
A review. The present contribution summarizes our previous investigations on the formation of emulsions, whose particles consist of a self-assembled inverted-type liq. cryst. phase or an inverted-type microemulsion. In this context, the main focus was on replacing either the dispersed oil droplets in normal O/W emulsions, or the kinetically stabilized internal W/O emulsion in double W/O/W emulsions, by an inverted-type liq. cryst. phase or an inverted-type microemulsion system. Owing to the physico-chem. properties of their internal nanostructures, these unique aq. dispersions are superior to conventional emulsions and double emulsions. They are attractive as nanonreactors and as host systems for solubilizing active mols. (drugs, flavors, and vitamins) in the cosmetics, pharmaceutical, and food industries. This chapter describes the effect of varying temp. and solubilizing oil on the reversible structural transitions of the internal nanostructures of these lipidic dispersions. [on SciFinder(R)]
Ben Achrai, Libster, Dima , Aserin, Abraham , and Garti, Nissim. . 2011. Solubilization Of Gabapentin Into Hii Mesophases.. Journal Of Physical Chemistry B, 115, 5, Pp. 825–835. doi:10.1021/jp108801d.
In the present work, we report on the solubilization of gabapentin (GBP) into lyotropic hexagonal mesophases composed of monoolein, tricaprylin, and water. It was demonstrated that the hexagonal structure remained intact up to 2 wt. % gabapentin, whereas the lamellar phase coexisted with the hexagonal one in the concn. range of 3-4 wt. % of the drug. At gabapentin content of 5-6 wt. %, only lamellar phases contg. defects such as dislocations and multilamellar vesicles were detected. Incorporation of GBP decreased the lattice parameter of the HII mesophase from 56.6 to 50.6 \AA, while the structural dimensions of the lamellar phase were not affected. ATR-FTIR anal. suggested enhanced hydrogen bonding between the protonated amine of GBP and the O-H groups of the GMO and the water surrounding in the inner hydrophilic interface region. This led to intercalation of the drug into the water-lipid interface. At higher GBP loads of 4-6 wt. %, thermal anal. revealed disordering within the lipid packing, apparently induced by the spatially altered interface area. Rheol. measurements correlated the macroscopic features of the systems with alterations on the mol. level and allowed distinguishing between closely related mesophases due to their different rheol. characteristics. In vitro transdermal delivery studies showed that the examd. mesophases enabled a sustained release of GBP compared to its aq. soln. Sustained release was more pronounced in the case of the hexagonal mesophase, compared to the lamellar one. [on SciFinder(R)]

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