Publications by Year: 2005

Nizri G, Magdassi S. Solubilization of hydrophobic molecules in nanoparticles formed by polymer-surfactant interactions. J. Colloid Interface Sci.Journal of Colloid and Interface Science. 2005;291 (1) :169 - 174.Abstract
The interaction between the anionic surfactant, Na dodecyl sulfate, and the polyelectrolyte, poly(diallyldimethylammonium chloride), may give nanoparticles dispersed in H2O. The morphol. of the resulting nanoparticles and their ability to solubilize hydrophobic mols. were evaluated. As shown by SEM and AFM imaging, the particles are spherical, having a diam. of ∼20 nm. The solubilization within the nanoparticles was tested with pyrene, a fluorescence probe, and Nile Red, a solvatochromic probe. For Nile Red the solubilization within the nanoparticles is at lower polarity than for SDS micelles, and from pyrene solubilization apparently the hydrophobicity of the nanoparticles depends on the ratio between the SDS mols. and the charge unit of the polymer. [on SciFinder(R)]
Magdassi S, Kahana F.; 2005. Biocompatible polymeric beads and use thereof.Abstract
The present invention relates to biocompatible polymeric beads and to biocompatible delivery systems comprising same for controlled or sustained release of bioactive mols. In particular, the invention relates to polymeric beads having a two-phase core and shell structure and to polymeric delivery systems comprising same that provide sustained release of the bioactive compd. A method of prepg. the biocompatible polymeric beads, comprises: (1) mixing an aq. soln. or suspension of the bioactive compd. in an oily phase to form a water-in-oil emulsion, in the presence of at least one surface active agent; (2) homogenizing the mixt.; (3) applying a polymeric shell around small droplets of the emulsion by means of core/shell extrusion; and (4) solidifying the shell to form two phase core-and-shell-structured polymeric beads. For example, both emulsion and suspension bead expts. were conducted with micronized halofuginone·HBr (I). A water-in-oil emulsion was prepd., in which the internal phase contained I and the oil was sunflower oil. Beads were formed by a core-shell double nozzle using a shell soln. contg. Na alginate and a crosslinking agent contg. CaCl2. [on SciFinder(R)]
Magdassi S, Cohn D.; 2005. Biocompatible polymeric delivery systems for sustained release of quinazolinones.Abstract
The present invention relates to biocompatible polymeric delivery systems for controlled or sustained release of quinazolinone derivs.(I; n = 1-2; R1 = H, halo, NO2, benzo, alkyl, Ph, alkoxy; R2 = OH, acetoxy, alkoxy; R3 = H, alkenoxy carbonyl), including the compd. halofuginone. In particular the invention relates to a polymeric delivery system comprising biocompatible polymeric beads having a two-phase core and shell structure, or polymeric films, beads or complexes that provide local sustained release of the pharmacol. agent. For example, polymeric emulsion beads with core/shell structure were prepd. for controlled release of halofuginone. A water-in-oil emulsion was prepd., in which the 20% wt. internal phase contained 50 mg halofuginone HBr/mL and the oil was sunflower oil. The emulsion was prepd. by adding the aq. halofuginone soln. in to the oil which contains 2.7% wt. span 80, and homogenized. Beads were formed by a core-shell double nozzle Innotek. The shell soln. was 2.5% sodium alginate and 2.5% silica in aq. soln. [on SciFinder(R)]
Bernath K, Magdassi S, Tawfik DS. Directed Evolution of Protein Inhibitors of DNA-nucleases by in Vitro Compartmentalization (IVC) and Nano-droplet Delivery. J. Mol. Biol.Journal of Molecular Biology. 2005;345 (5) :1015 - 1026.Abstract
In vitro compartmentalization (IVC) uses water-in-oil emulsions to create artificial cell-like compartments in which genes can be individually transcribed and translated. Here, we present a new application of IVC for the selection of DNA-nuclease inhibitors. We developed a nano-droplets delivery system that allows the transport of various solutes, including metal ions, into the emulsion droplets. This transport mechanism was used to regulate the activity of colicin nucleases that were co-compartmentalized with the genes, so that the nucleases were activated by nickel or cobalt ions only after the potential inhibitor genes have been translated. Thus, genes encoding nuclease inhibitors survived the digestion and were subsequently amplified and isolated. Selection is therefore directly for inhibition, and not for binding of the nuclease. The stringency of selection can be easily modulated to give high enrichments (100-500-fold) and recoveries. We demonstrated its utility by selecting libraries of the gene encoding the cognate inhibitor of colicin E9 (immunity protein 9, or Im9) for inhibition of another colicin (ColE7). The in vitro evolved inhibitors show significant inhibition of ColE7 both in vitro and in vivo. These Im9 variants carry mutations into residues that det. the selectivity of the natural counterpart (Im7) while completely retaining the residues that are conserved throughout the family of immunity protein inhibitors. The in vitro evolution process confirms earlier hypotheses regarding the "dual recognition" binding mechanism and the way in which new colicin-immunity pairs diverged from existing ones. [on SciFinder(R)]
Magdassi S, Sela Y, Cohen K.; 2005. Formulations for poorly soluble drugs comprising hydrophilic polymers.Abstract
The present invention provides a drug delivery system comprising nanoparticles or microparticles of a water poorly sol. drug dispersed in a polymeric bead contg. essentially only of hydrophilic polymers (i.e., without hydrophobic polymers). The present invention further provides a method of producing the drug delivery system of the invention. Thus, a 4% sodium alginate soln. was prepd. by mixing 16 g of sodium alginate and 400 g water together with 0.4 g of Bronopol (preservative) at about 37° until complete dissoln. A crosslinking agent was prepd. by dissolving 14.8 g of calcium chloride dihydrate in 1000 g water. An oil-in-water emulsion (20% oil phase, 80% aq. phase) was prepd. contg. 3% surfactant (mixt. of Tween 20 and Span 20, HLB = 10) and 3.3584 g of simvastatine powder (a poorly sol. drug) in 80.0 g toluene. To a mixt. of 95.1 g of 4% sodium alginate soln. and 3.8 g of silica used to prevent shrinking upon drying, was added 95.1 g of the o/w emulsion and stirred together until homogeneous mixt. was achieved. The alginate-emulsion mixt. was introduced into encapsulator and jetted into 100 mM CaCl2 crosslinking soln. to obtain simvastatine beads. [on SciFinder(R)]
Aharoni A, Amitai G, Bernath K, Magdassi S, Tawfik DS. High-Throughput Screening of Enzyme Libraries: Thiolactonases Evolved by Fluorescence-Activated Sorting of Single Cells in Emulsion Compartments. Chem. Biol. (Cambridge, MA, U. S.)Chemistry & Biology (Cambridge, MA, United States). 2005;12 (12) :1281 - 1289.Abstract
Single bacterial cells, each expressing a different library variant, were compartmentalized in aq. droplets of water-in-oil (w/o) emulsions, thus maintaining a linkage between a plasmid-borne gene, the encoded enzyme variant, and the fluorescent product this enzyme may generate. Conversion into a double, water-in-oil-in-water (w/o/w) emulsion enabled the sorting of these compartments by FACS, as well as the isolation of living bacteria cells and their enzyme-coding genes. We demonstrate the directed evolution of new enzyme variants by screening >107 serum paraoxonase (PON1) mutants, to yield 100-fold improvements in thiolactonase activity. In vitro compartmentalization (IVC) of single cells, each carrying >104 enzyme mols., in a vol. of <10 fL (fl), enabled detection and selection despite the fast, spontaneous hydrolysis of the substrate, the very low initial thiolactonase activity of PON1, and the use of difusable fluorescent products. [on SciFinder(R)]
Magdassi S, Eron G, Vinetsky Y.; 2005. Ink for ceramic surfaces.Abstract
The present invention concerns ink for printing on ceramic surfaces such as glass, which contains glass frits for silica nanoparticles and optionally a pigment beside ordinary components such as binders, pigments, additives and solvents, and is suitable for ink jet printing. A such ink will fuse to the substrate upon firing, and is characterized by: (a) having viscosity bellow 20 cPs at jetting temp. and (b) becoming an integral part of the substrate upon exposure to temps. above 500°. [on SciFinder(R)]
Kamyshny A, Ben-Moshe M, Aviezer S, Magdassi S. Ink-jet printing of metallic nanoparticles and microemulsions. Macromol. Rapid Commun.Macromolecular Rapid Communications. 2005;26 (4) :281 - 288.Abstract
Two types of ink-jet inks are presented: ink contg. an aq. dispersion of silver nanoparticles and an oil-in-water microemulsion-based ink. The metallic ink contains nanoparticles of silver, which are formed in the presence of an ionic polymeric stabilizer. Sintering of the printed image obtained with the use of such silver-based inks at temps. as low as 300° C results in formation of patterns possessing noticeable cond. The microemulsion inks are based on a thermodynamically stable microemulsion, in which the dispersed oil phase is a volatile solvent contg. a water-insol. colorant. After contact of the jetted ink droplets with a substrate, nanodroplets of the microemulsion are converted into nanoparticles of the solubilized colorant. In some cases, it was found that the evapn. of microemulsion ink droplets leads to formation of rings composed of ordered nanoparticles. [on SciFinder(R)]
Tawfik D, Bernath K, Aharoni A, Peisajovich S, Griffiths AD, Mastrobattista E, Magdassi S.; 2005. Methods for in vitro sorting of molecular and cellular libraries, such as a gene library, that are microencapsulated using water-in-oil-in-water emulsions.Abstract
The present invention provides an in vitro system for compartmentalization of mol. or cellular libraries and provides methods for selection and isolation of desired mols. or cells from the libraries. The library includes a plurality of distinct mols. or cells encapsulated within a water-in-oil-in-water (w/o/w) emulsion. The emulation includes a continuous external aq. phase and a discontinuous dispersion of water-in-oil droplets. The internal aq. phase of a plurality of such droplets comprises a specific mol. or cell that is within the plurality of distinct mols. or cells of the library. According to a first aspect the present invention provides a gene library comprising a plurality of re-emulsified water-in-oil droplets, each droplet comprises an external water phase surrounding a central water-in-oil droplet, the internal water phase within each droplet comprises a genetic element, in vitro transcription-translation reaction system. To ensure that the genetic elements and gene products may not diffuse between primary water-in-oil droplets or between re-emulsified water-in-oil droplets, the-contents of each droplet must be isolated from the contents of the surrounding droplets, so that there is no or little exchange of gene products between the droplets over the timescale of the expt. The method of the present invention requires that there are only a limited no. of genetic elements per droplet. This ensures that the gene product of an individual genetic element will be isolated from other genetic elements. Finally, the formation and the compn. of the droplets must not interrupt with the function of the expression machinery of the genetic elements and the activity of the gene products. Prepn. and sorting of w/o/w emulsions by FACS (fluorescence-activated cell sorting) were demonstrated using lacZ reporter selection from a pool of lacZ gene mutants. Compartmentalization and detection of PON1 (serum paraoxonase) gene variants in single Escherichia coli cells were also demonstrated. [on SciFinder(R)]
Magdassi S, Spernath L.; 2005. Preparation of nanoparticles from nanoemulsions and nanoparticles of an active agent.Abstract
The prodn. of nanoparticles from oil-in-water nanoemulsions, occurs by phase inversion techniques. The phase inversion may be achieved by using a const. temp., where the inversion occurs by continuous addn. of H2O or by varying the temp. involving heating and rapid cooling. More specifically, the process comprises (a) mixing the active agent (e.g. monomer) with a volatile solvent and ≥1 nonionic surfactant, (b) adding to the mixt. of (a) an aq. phase to form a water-in-oil emulsion, (c) continuously adding to the emulsion of (b) water at a rate enabling phase inversion and formation of oil-in-water nanoemulsion, (d) evapg. the volatile solvent from the oil-in-water nanoemulsion of (c) to obtain nanoparticles. The formation of lauryl acrylate polymer nanoparticles was demonstrated in the presence of Brij 96v. [on SciFinder(R)]
Magdassi S, Grouchko M, Toker D, Kamyshny A, Balberg I, Millo O. Ring Stain Effect at Room Temperature in Silver Nanoparticles Yields High Electrical Conductivity. LangmuirLangmuir. 2005;21 (23) :10264 - 10267.Abstract
We demonstrate that metallic rings formed spontaneously at room temp. via evapn. of aq. drops contg. silver nanoparticles (20-30 nm in diam.) exhibit high elec. cond. (up to 15% of that for bulk silver). The mechanism underlying this self-assembly phenomena is the "ring stain effect", where self-pinning is combined with capillary flow to form a ring consisting of close-packed metallic nanoparticles along the perimeter of a drying droplet. Our macroscopic and microscopic (applying conductive at. force microscopy) transport measurements show that the cond. of the ring, which has a metallic brightness, is orders of magnitude larger than that of corresponding aggregates developed without the ring formation, where high cond. is known to appear only after annealing at high temp. [on SciFinder(R)]