Publications by Year: 1998

Magdassi S, Yang A, Tao C, Desai NP, Yao Z, Soon-Shiong P.; 1998. Total nutrient admixtures as stable multicomponent liquids or dry powders and methods for the preparation thereof.Abstract
Disclosed are stabilized total nutrient admixt. (TNA) compns. useful for parenteral delivery of pharmacol. acceptable lipids or fats as well as methods for the prepn. thereof. In particular, the pharmacol. acceptable lipid or fat is contained within a protein-walled shell. In a particular embodiment of the invention, a TNA compn. using human serum albumin (HSA) as a stabilizer has been prepd. as a convenient three-in-one formulation (i.e., contg. a fat emulsion, dextrose, and amino acids plus electrolytes). This "three-in-one" formulation can be prepd. in liq. form or in dry form (comprising submicron-sized nanoparticles). The dried material is stable, even under long-term storage, and is easily reconstituted immediately before use by simply adding sterile water (with or without vitamin supplementation). This serves to rehydrate the powder into a TNA suitable for injection. The long-shelf life, ease of reconstitution, and single-component injectability of invention compns. provide significant cost savings, as such compns. can be reconstituted and administered safely, even in the home. In addn., HSA, the stabilizing agent of choice for use in the practice of the present invention, has been shown to improve survival and wellness when given as a supplement to patients receiving conventional forms of total nutrient admixts. Thus, 15 mL of 10 % amino acid soln. (FreAmine III), 4.3 mL of 70 % dextrose soln., 0.5 mL phosphate buffer, 0.4 mL KCl (2 M), NaCl (4 M), 0.5 mL MgSO4 (0.406 M), 0.5 mL Na citrate (10 %), 0.5 mL Ca gluconate (0.46 M) were mixed with 0.25 g of HSA until a clear soln. was obtained. The soln. was filtered and 2.5 mL soybean oil was added to the aq. soln. and the mixt. was homogenized (condition was detailed). The emulsion was stored under N in a polypropylene test tube for 1 wk at 4°, followed by one day at room temp.; the droplet size was not changed and there were no signs of oil sepn. or creaming. [on SciFinder(R)]
Kamyshny A, Magdassi S. Chemiluminescence immunoassay in microemulsions. Colloids Surf., BColloids and Surfaces, B: Biointerfaces. 1998;11 (5) :249 - 254.Abstract
A novel chemiluminescence immunoassay which combines microparticles and microemulsion is described. The method is based on a specific interaction of an antibody with an antigen preadsorbed onto fluorescer (perylene) microparticles (mean diam. 0.8-1.6 μm). Dissolving the particles in a microemulsion-forming mixt. contg. bis(2,4,6-trichlorophenyl) oxalate in toluene (oil phase) and H2O2 in Triton X-100 (surfactant)/2-butanol (cosurfactant)/water leads to chemiluminescence. The dependence of the chemiluminescence intensity on the concns. of antigen, antibody and fluorescer, as well as the kinetics of the chemiluminescence decay, were studied. [on SciFinder(R)]
Toledano O, Magdassi S. Emulsification and foaming properties of hydrophobically modified gelatin. J. Colloid Interface Sci.Journal of Colloid and Interface Science. 1998;200 (2) :235 - 240.Abstract
Surface active gelatins were formed by covalent attachment of hydrophobic groups to gelatin mols. by reacting N-hydroxysuccinimide esters of various fatty acids (C4-C16) with the lysine groups. The surface activity was evaluated by emulsification and foaming properties, and by adsorption at the oil-H2O interface. In general, the modified gelatins are more surface active than the native gelatin. The increase in hydrophobic chain length and the no. of attached alkyl chains per gelatin mol. decreases the emulsion droplet's size and to more stable emulsions. Adsorption isotherms, at the o/w interface, show much higher surface concn., at satn., of the modified gelatin than the native gelatin. The modified gelatins also have high foaming ability and a high foam stability, while the maximal foam activity was obtained by the C8 modified gelatin. The foaming properties of the surface-active gelatins were also compared to that of Na dodecyl sulfate (SDS) and below the CMC of SDS, both foam activity and stability were higher for the modified gelatins. However, above the CMC the foam activity of SDS was higher, but the foam stability was lower than for C8-C16-modified gelatins. [on SciFinder(R)]
Magdassi S, Mumcuoglu K, Bach U, Rosen Y.; 1998. Method of making positively charged microcapsules of emulsions of oils and its uses.Abstract
The invention relates to a process for prepg. a chitosan-contg. microcapsules and emulsions of an oil including the steps of (a) forming an oil-in-water emulsion by homogenizing the oil into an aq. soln. contg. an anionic emulsifier; and (b) adding to the emulsion obtained in (a) an aq. chitosan soln. while continuously homogenizing the mixt. to give a stable emulsion, which is converted into microcapsules by using the proper electrolyte and pH changes. Also encompassed are prepns. including as active ingredient a lice repelling agent, vitamin E or a UV radiation photoprotectant. The prepns. may be sustained-release or long-acting prepns. Rosemary oils were dropwise added into a lecithin soln. in water in a homogenizer to obtain a white emulsion, to which a chitosan soln. (prepd. by dissolving chitosan into a citric acid soln.) was added. The final compn. (pH 3.5) contained rosemary oil 15, chitosan 0.5, citric acid 5, lecithin 0.35, and water 79.15 %. An excellent lice repellency of the emulsion was demonstrated. [on SciFinder(R)]
Magdassi S, Desai N, Ferreri K, Soon-Shiong P.; 1998. Methods for the production of protein particles useful for delivery of pharmacological agents.Abstract
A method has been developed for the formation of submicron particles (nanoparticles) by heat-denaturation of proteins (such as human serum albumin) in the presence of multivalent ions (such as calcium). Also provided are novel products produced by the invention method. An appropriate concn. of multivalent ions, within a relatively narrow range of concns., induces the pptn. of protein in the form of colloidal particles, at a temp. which is well below the heat denaturation temp. of the protein (as low as 60 °C for serum albumin). Temps. at which invention method operates are sufficiently low to permit incorporation of other mols. (e.g., by co-pptn.), into submicron particles according to the invention, including compds. which cannot withstand high temps. Invention methods facilitate the prodn. of protein nanoparticles and microparticles contg. various mols. (such as nucleic acids, oligonucleotides, polynucleotides, DNA, RNA, polysaccharides, ribozymes, pharmacol. active compds., and the like) useful for therapeutic, diagnostic and other purposes. The addn. of multivalent cations serves both to induce pptn., and to allow linking of neg. charged mols., such as DNA, to the neg. charged protein. Microparticles and nanoparticles were formed from albumin in the presence of CaCL2. [on SciFinder(R)]
Vinetsky Y, Magdassi S. Properties of complexes and particles of gelatin with ionic surfactants. Colloid Polym. Sci.Colloid and Polymer Science. 1998;276 (5) :395 - 401.Abstract
The properties of sol. gelatin-ionic surfactant complexes and insol. particles were evaluated. Colloidal particles of gelatin A-cationic surfactant (dodecyltrimethylammonium bromide, DTAB, and cetyltrimethylammonium bromide, CTAB) were formed. Binding isotherms showed that these particles are obtained above the CMC of each surfactant, while cooperative binding takes place. Surface tension measurements conducted for both gelatin/DTAB and gelatin/anionic surfactant, SDS, a break in the curve describing surface tension vs. no. of bound surfactant mols., (ν) at concns. below the CMC of each surfactant alone. This break, which is attributed to CMC 1, is obsd. at the same no. of bound surfactant mols. (ν = ≈2) for both gelatin/surfactant couples. Contact angle measurements showed that the max. hydrophobicity of the gelatin-surfactant particles is obtained at the same concn. range in which the pptn. occurs. Also the hydrophobicity of gelatin-SDS particles is higher than that of the gelatin-cationic surfactants, due to a different compn. of the resulting particles. The zeta potential of the particles indicated charge neutralization and even charge reversal for gelatin-CTAB at high surfactant concn. [on SciFinder(R)]
Desai NP, Tao C, Yang A, Louie L, Zheng T, Yao Z, Soon-Shiong P, Magdassi S.; 1998. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof.Abstract
Compns. are provided for the in vivo delivery of substantially water-insol. pharmacol. active agents (such as the anticancer drug paclitaxel) in which the pharmacol. active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacol. active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diam. of less than about 1 μ. The use of specific compn. and prepn. conditions (e.g., addn. of a polar solvent to the org. phase), and careful selection of the proper org. phase and phase fraction, enables the reproducible prodn. of unusually small nanoparticles of less than 200 nm diam., which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry power comprising nanoparticles of water-insol. drug coated with a protein, and free protein to which mols. of the pharmacol. agent are bound. This results in a unique delivery system, in which part of the pharmacol. active agent is readily bioavailable (in the form of mols. bound to the protein), and part of the agent is present within particles without any polymeric matrix therein. Albumin nanoparticles contg. paclitaxel were prepd. by high pressure homogenization. [on SciFinder(R)]