# Peer Review Publications

Liron Bitan-Cherbakovsky, Dima Libster, Maria Francesca Ottaviani, Abraham Aserin, and Nissim. Garti. 2012. “Structural Behavior and Interactions of Dendrimer within Lyotropic Liquid Crystals, Monitored by EPR Spectroscopy and Rheology.” Journal of Physical Chemistry B, 116, 8, Pp. 2420–2429. Abstract
Micro- and macrostructural behaviors of three different lyotropic liq. crystals (LLCs) loaded with a dendrimer, namely second generation poly(propylene imine) (PPI-G2), were studied by rheol. and ESR (EPR). The three mesophases were L$\alpha$, Q224, and HII composed of glycerol monooleate (GMO) and water-PPI-G2 soln. (and d-$\alpha$-tocopherol (vitamin E) in the case of HII). We characterized the impact of PPI-G2 interactions with the components of the host mesophases on their structural characteristics on different length scales. The incorporation of PPI-G2 within the L$\alpha$ and HII systems induced the formation of more elastic hexagonal systems with a solid-like behavior, while in the Q224 system a different trend with a liq.-like behavior was obsd. As a result, the dendrimer induced a remarkable change in both the structural and viscoelastic properties of the systems. Hence, the microenvironment in the interface region within the systems was monitored by computer-aided EPR using 5-doxylstearic acid (5-DSA) as a pH-dependent probe. The microviscosity ($\tau$) and order (S) of systems were sensitive to the PPI-G2 presence: when PPI-G2 concn. increased, $\tau$ and S increased in both the L$\alpha$ and Q224 systems. In the HII systems two trends were obsd., reflecting a decrease in $\tau$ and S up to 10 wt.% PPI-G2 and subsequently their increase at higher dendrimer concns. PPI-G2 interacted strongly with the GMO hydroxyl groups in the L$\alpha$ phase, with the water mols. in the Q224 systems. In the HII mesophase strong interactions with both the water and GMO hydroxyl mols. were detected. [on SciFinder(R)]
Debby P Chang and Tommy. Nylander. 2012. “Nonlamellar lipid liquid crystalline structures at interfaces.” In Self-Assem. Supramol. Archit., Pp. 289–318. John Wiley & Sons, Inc. Abstract
A review. Nonlamellar lipid-based liq. cryst. structures, such as cubic, hexagonal, and sponge phases, have potential as delivery systems in pharmaceutical, food, and cosmetic applications. This is due to the space-dividing nature of these phases, which features mono- or bicontinuous networks of both hydrophilic and hydrophobic domains. To utilize these nonlamellar liq. cryst. structures as delivery vehicles, it is crucial to understand how they interact with and respond to different types of interfaces. The progress in the area of liq. cryst. lipid-based nanoparticles opens up new possibilities for prepn. of well-defined surface films with well-defined nanostructure. Apart from the relevance to drug delivery, such studies create opportunities for new applications for functionalized and tunable surface coatings as well. This review will focus on recent progress in the formation of nonlamellar dispersion and its interfacial properties at the solid-liq. and biol. relevant interfaces. Various exptl. techniques on the study of interfacial interactions of these cryst. structures will be discussed. [on SciFinder(R)]
Marganit Cohen-Avrahami, Dima Libster, Abraham Aserin, and Nissim. Garti. 2012. “Penetratin-induced transdermal delivery from HII mesophases of sodium diclofenac.” Journal of Controlled Release, 159, 3, Pp. 419–428. Abstract
Penetratin, a cell penetrating peptide is embedded within a reversed hexagonal (HII) mesophase for improved transdermal delivery of sodium diclofenac (Na-DFC). The HII mesophase serves as the solubilization reservoir and gel matrix whereas penetratin is the transdermal penetration enhancer for the drug. The systems were characterized and the interactions between the components were detd. by SAXS, ATR-FTIR and SD-NMR. High affinity of Na-DFC to glycerol monooleate (GMO) was revealed, assocd. with increasing the order within the water channels. This affinity is enhanced upon heating and seems to be assocd. with GMO dehydration. Penetratin (PEN) is entrapped at the hydrophilic region of the HII mesophase, between the GMO headgroups, reducing the order of the system and decreasing the size of the hexagonal domains. The transdermal delivery rate of Na-DFC through porcine skin, from the HII mesophases, was enhanced by PEN and so also the cumulative transport crossing the skin. PEN induced accelerated drug diffusion through the stratum corneum, towards the different skin layers. The transdermal delivery enhancement is explained from the results of the ATR-FTIR anal. It seems that PEN accelerates the structural transition of skin lipids from hexagonal to liq. The disordering results in enhanced diffusion of Na-DFC through the stratum corneum, followed by enhanced overall penetration of the drug. [on SciFinder(R)]
Massimo Bonini and Pierandrea. Lo Nostro. 2012. “Micelle formation: thermodynamic aspects and characterization.” In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 31–49. DEStech Publications, Inc. Abstract
A review. The most prominent feature of surfactants is their ability to self-assoc. and form discrete aggregates in aq. dispersions. Among the various self-assembled structures that are produced (vesicles, membranes, liq. crystals, etc.), micelles represent the simplest class of assocn. colloids, and are widely used as nano-architectures for different applications. In spite of the vast literature, a complete understanding of all the exptl. evidences related to the micellization process is still a work in progress. In particular, the thermodn. and kinetics of micellization provide the crucial concepts for the control of dissocn. and reconstruction of micelles, such as in the solubilization, stabilization and delivery of active ingredients, and in cosmetics, detergents, food technol., and in pharmaceutical formulations. In this contribution, we offer an overview of the various structures formed by self-assembling amphiphilic mols. in water. The basic thermodn. involved in self-assembly is described, and an overview of the exptl. techniques used in the characterization of the structure and properties of these nanostructures is given. [on SciFinder(R)]
Nir Debotton and Simon. Benita. 2012. “Characterization and therapeutic applications of immunonanoparticles as targeted drug delivery systems: a focus on cancer therapy.” In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 303–339. DEStech Publications, Inc. Abstract
A review on immunonanoparticles (immunoNPs) as promising drug-targeting, colloidal carriers, that can ensure the specific recognition of the antigen site and, using the colloidal delivery system, release cytotoxic agents close to the inaccessible pathol. target tissues-over-expressing tumor antigen. The main approaches used for the coupling of monoclonal antibodies (MAbs) to NPs are reviewed. In addn., the preclin. achievements of NP formulations conjugated to various MAbs are described and updated. Also addressed is the synergistic importance of the MAbs as targeting moieties on immunoNP formulations as compds. that not only target specific pathol. organs, but also ensure increased therapeutic activity of the drug-loaded NPs by actually internalizing them within the desired cells. [on SciFinder(R)]
N Garti and A Aserin. 2012. “Micelles and microemulsions as food ingredient and nutraceutical delivery systems.” Woodhead Publishing Series in Food Science, Technology and Nutrition, 239, Encapsulation Technologies and Delivery Systems for Food Ingredients and Nutraceuticals, Pp. 211–251. Abstract
A review. Microemulsions are considered excellent delivery vehicles for bioactives, food additives and food supplements. They offer the advantages of spontaneous formation, ease of manuf., thermodn. stability, very low viscosity and Newtonian properties, full transparency (clear solns.) and improved solubilization capacities of bioactive materials. This chapter explores some of the new trends in microemulsion research, including many carried out in our lab, through anal. of some representative studies. The solubilization of different food additives such as flavoring agents, aromas, antioxidants, and colorants, as well as peptides and nutraceuticals, in various microemulsion compns. and microstructures are reviewed. [on SciFinder(R)]
Nissim Garti and Rachel. Lutz. 2012. “Double emulsions.” In Encycl. Surf. Colloid Sci. (2nd Ed.), Pp. 1816–1845, 30 pp. Taylor & Francis. Abstract
A review provides better understanding of the stabilizing mechanisms and pathways and a better control of the release patterns from double emulsions. It discusses the different approaches such as stability considerations, instability pathways, release and transport phenomenon. [on SciFinder(R)]
Nissim Garti, Dima Libster, and Abraham. Aserin. 2012. “Lipid polymorphism in lyotropic liquid crystals for triggered release of bioactives.” Food & Function, 3, 7, Pp. 700–713. Abstract
In this review the authors present recent progress on lyotropic liq. crystals (LLC) as delivery vehicles for cosmetoceuticals, nutraceuticals, and drugs. LLC were known for decades and their potential as delivery vehicles is well recognized. Yet, the 2 major mesophases, reverse hexagonal (HII) and bicontinuous cubic (primitive, gyroid, and diamond), are relatively hard gels with very slow release kinetics of the bioactives. In recent years a discontinuous cubic micellar mesophase (QL) was characterized and studied, showing significant potential as a delivery vehicle. In addn., the HII mesophase formed could be much more fluid and produced at room temp. Recent studies concd. on establishing methods to evaluate solubilization capacity and relationship between the diam. and length of the cylinders and the nature of the solubilizates. Special attention was given to finding methods to target the vehicles to the lumen and to trigger the release of the bioactives. This review summarizes the efforts of the authors' group along with work by numerous other scientists in this area. All these efforts suggest that the lyotropic mesophases and the corresponding dispersed soft particles (cubosomes, hexosomes, micellosomes) are now more than ever ready to become drug delivery vehicles for transport across the skin and the gut. [on SciFinder(R)]
Nissim Garti, Geut Hoshen, and Abraham. Aserin. 2012. “Lipolysis and structure controlled drug release from reversed hexagonal mesophase.” Colloids and Surfaces, B: Biointerfaces, 94, Pp. 36–43. Abstract
The present work investigates a system composed of a ternary reversed hexagonal mesophase (HII) loaded with a lipase for modulating drug delivery capabilities of the system. Thermomyces lanuginosa lipase was solubilized into HII mesophase for the benefits of continuing lipolysis of the lipids, consequently disordering and decompg. the hexagonal mesophase and thereby enhancing the diffusion of the encapsulated drug. A single transition from the HII structure to a random micellar phase was detected during the lipolysis. In the first lipolysis stage the hexagonal system (glycerol monooleate, tricaprylin, and water) preserved its symmetry within ca. 200 min. During this step about 40-60% molar of the lipids were hydrolyzed, and a gradual shrinking of the HII cylinders (decrease of 8 \AA in lattice parameter) was detected. In the second lipolysis stage, the HII mesophase gradually disintegrated (faster rate) and the release of a model drug (sodium diclofenac) was significantly enhanced, which was assumed to be lipolysis rate-controlled. After about 15 h the HII mesophase was disintegrated into two dispersed immiscible phases. The release obeyed two-step Higuchi kinetics with two consecutive linear correlations of the drug release. [on SciFinder(R)]
Claire Geral, Angelina Angelova, Sylviane Lesieur, Borislav Angelov, and Valerie. Nicolas. 2012. “Multicompartment lipid nanocarriers for targeting of cells expressing brain receptors.” In Self-Assem. Supramol. Archit., Pp. 319–355. John Wiley & Sons, Inc. Abstract
A review. Neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), are essential for the development and survival of human neurons. Their encapsulation in carrier lipid systems is anticipated to overcome the problems resulting from the pharmacokinetics of peptides in the cerebral circulation. Lipid nanocarriers contg. an omega-3 polyunsatd. fatty acid [eicosapentaenoic acid] (EPA), showing neuroprotective effects, should trigger the BDNF activity. The purpose of this study is to design and characterize self-assembled lipid systems suitable for encapsulation and potentiation of neurotrophic peptide activity and study of multicompartment liq. cryst. formulations in vitro on a human neuronal cell line expressing BDNF receptors. Sterically stabilized nanodispersed lipid systems are prepd. from a PEGylated (polyethylene glycol) liq. cryst. phase in excess water. Such lipid nanovectors, derived by self-assembly, are of ongoing interest thanks to their biocompatible compns. and the relatively low energy input required for their manuf. The latter is an essential factor for the encapsulation of fragile and temp.-sensitive peptide mols. Having induced the differentiation of a human neuroblastoma cell line SH-SY5Y, as a model of neurodegeneration, we examine in vitro the expression of the TrkB brain receptor of neurotrophins and the cytotoxicity of the designed multicompartment lipid nanocarriers to neuronal cells. [on SciFinder(R)]
Patrick G Hartley and Hsin-Hui. Shen. 2012. “Nanocharacterization of lyotropic liquid crystalline systems.” In Self-Assem. Supramol. Archit., Pp. 97–127. John Wiley & Sons, Inc. Abstract
A review. The development of techniques for the characterization of the nanostructure of lyotropic liq. cryst. systems were crucial in enabling increased understanding of fundamental properties and efficacy in technol. applications. Provided is a review of a no. of commonly used and emerging nanocharacterization techniques, with a view to providing a resource for academic and industrial researchers joining the field. [on SciFinder(R)]
Roy E Hoffman, Abraham Aserin, and Nissim. Garti. 2012. “New insights into the microemulsion-based chromatographic NMR resolution mechanism and its application to fragrance/flavor molecules.” Journal of Magnetic Resonance, 220, Pp. 18–25. Abstract
The NMR chromatog. method is applied to a class of mols. with similar phys. properties. We correlate the sepn. ability of microemulsions to the phys. properties of the analyzed mols. Flavor and aroma compds. are very widespread. Compositional anal. is in many cases tedious. Any new method of anal. is always useful and challenging. Here we show a new application to a class of fragrance mols., with only a moderate variation in their chem. and phys. characteristics. Up to 11 selected compds. in one mixt. are resolved in one spectrum by NMR chromatog., despite the similarity of the compds. The differences between O/W and W/O microemulsions and their resoln. mechanism as applied to fragrance mols. are explained in terms of hydrophilicity and lipophilicity and effective crit. packing parameters of the microemulsions. The obsd. diffusion rates are shown to correlate with solvation parameters. These results can be used to est. the diffusion rates of mols. to be sepd., allowing selection of the microemulsion or NMR chromatog. solvent appropriate for each specific application. [on SciFinder(R)]
Owen Griffith Jones and Julian. D McClements. 2012. “Development of colloidal delivery systems for food and pharmaceutical applications based on proteins and polysaccharides.” In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 81–123. DEStech Publications, Inc. Abstract
A review. There is an increasing tendency towards the development of food, cosmetic and pharmaceutical products contg. only natural ingredients. Many proteins and polysaccharides extd. from nature can be used as functional ingredients to form colloidal systems suitable for use in industrial products. These colloidal systems can be fabricated using a variety of physicochem. and processing approaches. This chapter focuses on the fabrication and properties of sub-micron to micron-sized colloidal particles, formed by controlled aggregation/complexation of mixed biopolymer systems. The processes used to fabricate these particles include treatments of globular protein and/or polysaccharide solns. at select temps., pH, ionic strengths, and/or solvent qualities. Potential applications of the biopolymer colloidal particles are discussed. [on SciFinder(R)]
Barbara Klajnert and Maria. Bryszewska. 2012. “Dendrimeric polymers for pharma applications - anti-cancer therapies.” In Nanotechnol. Solubilization Delivery Foods, Cosmet. Pharm., Pp. 367–381. DEStech Publications, Inc. Abstract
A review. During the last twenty years dendrimers have attracted wide interest as potential therapeutics. These novel macromols. differ in many ways from traditional polymers. Dendrimers are globular, possessing a core mol. to which layers of branched monomers are attached. The no. of layers is described by so-called generations. The structure of dendrimers results in plenty of terminal surface groups and empty internal cavities. Both these features are important when considering dendrimers for biomedical applications. Moreover, precise methods of synthesis enable the tailoring of dendrimers to specific purposes. In this concise review, a few examples of the part dendrimers play in anti-cancer therapies will be presented. It is worth stressing that these examples of pharma applications of dendrimers do not include all areas of study that are presently being conducted, and that each year produce new ways to use dendrimers in medicine. [on SciFinder(R)]