New approaches for creation of novel protein-based colloidal and micellar systems are presented. These systems consist of colloidal clusters of chem. modified (hydrophobized) proteins or surfactant aggregates (micelles) contg. incorporated biol. catalysts - enzymes, or mols. capable of specific recognition - antibodies. The principles of formation, functional properties as well as practical applications of the protein-based colloidal and micellar systems in the fields of chem. synthesis, chem. anal., immunodiagnostics, drug targeting and biosensors are discussed. [on SciFinder(R)]

The penetrant ability of the native glucose oxidase, GOx, and of the hydrophobically modified enzyme GO(mod) realized by grafting to its lysine residues alkyl C16 chains, into phosphatidylcholine dibehenoyl (DBPC), phosphatidylcholine dipalmitoyl (DPPC), phosphatidyl-ethanolamine dipalmitoyl (DPPE), phosphatidylserine dipalmitoyl (DPPS), and cholesterol (CHOL) monolayers was assessed by surface pressure measurements at const. area by enzyme injection to the aq. phase beneath spread monolayers. As revealed by the magnitude of surface pressure increments (ΔΠ), both the quantities and the rates of penetration of the enzymes into these monolayers were lipid chem. nature and enzyme concn. dependent. When compared with GOx, GO(mod) displayed an enhanced penetrant ability into all the studied monolayers that resulted in rapidly attained ΔΠ plateau values, characteristic of stable systems. The influence of lipid hydrocarbon chain length and of the polar headgroup charge on the efficiency and effectiveness of GOx and GO(mod) penetration into these monolayers is discussed. (c) 1999 Academic Press. [on SciFinder(R)]

In accordance with the present invention, there are provided compns. and methods useful 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 μm. 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 powder 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. [on SciFinder(R)]

Stabilized total nutrient admixt. (TNA) compns. are useful for the in vivo parenteral delivery of pharmacol. acceptable lipids or fats. The lipid or fat is contained within a protein walled shell. Thus, a TNA compn. using human serum albumin (HSA) as a stabilizer is 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 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, is known to improve survival and wellness when given as a supplement to patients receiving conventional forms of total nutrient admixts. [on SciFinder(R)]

Covalent modification of human IgG and gelatin (type A) by fatty acid esters (C8, C12 and C16) of N-hydroxysuccinimide was carried out. Prepns. of hydrophobized IgG contg. 9 and 25 attached caprylic and 25 palmitic chains and prepns. of gelatin with low and high degree of modification were obtained. The adsorption of unmodified and modified proteins at a hydrophobic surface obtained by coating silica with a phosphatidyl choline monolayer was studied. It was found that an increase in the proteins' hydrophobicity leads to an increase in their adsorption detg. by hydrophobic binding which overcomes the electrostatic repulsion between the neg. charged surface and the neg. charged protein mols. An increase in the IgG hydrophobicity also resulted in the formation of a more compact monolayer. An increase in gelatin adsorption after its hydrophobization led to either the formation of a more compact monolayer or the formation of a more condensed mol. configuration after attachment of alkyl chains. For both proteins the adsorption can be accompanied by penetration of these chains into the phospholipid monolayer. [on SciFinder(R)]

Covalent modification of glucose oxidase from Aspergillus niger by the palmitic acid ester of N-hydroxysuccinimide at a molar ratio ester:protein of 56:1 results in the formation of the enzyme deriv. with 11 attached palmitic chains. Surface hydrophobicity measurements by a fluorescent probe, 8-anilino-1-naphthalenesulfonate, indicate a drastic increase in the hydrophobicity index of glucose oxidase after such a modification. The modified glucose oxidase displays a much higher adsorption affinity for hydrophilic (silica) as well as for hydrophobic (silica coated by phosphatidyl choline and cholesterol monolayers and polystyrene latex beads) surfaces, and forms more compact surface layers compared to the native glucose oxidase. Such a difference results from a spontaneous formation of micelle-like aggregates (clusters) of the hydrophobized enzyme mols. (av. size 500 nm), which come into contact with a surface. A possible structure of the glucose oxidase surface layers and the nature of the forces detg. the adsorption of the enzyme on various adsorbents are discussed. (c) 1999 Academic Press. [on SciFinder(R)]

Covalent modification of human IgG by fatty acid esters (C8 and C16) of N-hydroxysuccinimide was carried out. Surface hydrophobicity measurements, using the fluorescent probe 8-anilino-1-naphthalenesulfonate, indicate an increase in the surface protein hydrophobicity with an increase in the no. and in the length of the attached alkyl chains. The modified IgGs decrease surface tension at the air/soln. interface more effectively than the native protein. The values of the mol. cross-sectional areas (ΔA) estd. from the kinetic data are at 100-300 Å2 and reflect the size of protein segments at the interface during the adsorption process. About 40-50% increase in the ΔA was obsd. upon attachment of the C8 groups to the native IgG. The lengthening of the bound alkyl chain from C8 to C16 results in a further increase in this value. The influence of the overall IgG hydrophobicity and the length of the attached alkyl chain on the dimensions of the mobile protein segment at the surface are discussed. (c) 1999 Academic Press. [on SciFinder(R)]

The present invention relates to a gel compn. useful for skin care and protection comprising up to 80 % wt./wt. Dead Sea water, hydrophobic and/or hydrophilic active agents, solubilizers, gelling agents or viscosity modifiers and water to complete up to 100 %. Preferably, the compn. is a clear liq. gel. In the compn. of the present invention the hydrophobic active agents may be vegetable oils, free fatty acids or vitamins, or any combination thereof and the hydrophilic active agent may be humectants, α-hydroxy acids, anti irritant agents, plant exts., moisturizing agents or hydrolyzed plant proteins or any combination thereof. The gel may further comprise antioxidants and fragrances. A compn. contained Dead Sea water 75.0, oleth 20 3.0, glycereth 26 2.0, hydroxyethyl cellulose 0.8, tocopheryl acetate 0.3, lavender oil 0.3, BHA 0.1 and deionized water to 100%. [on SciFinder(R)]

In accordance with the present invention, there are provided compns. and methods useful 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 <1 μm. 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 <200 nm diam., which can be sterile-filtered. The particulate system produced can be converted into a redispersible dry powder 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. [on SciFinder(R)]