Nanocapsules having a polyelectrolyte envelope
AssigneeNovosom AG
InventorsSteffen Panzner, Gerold Endert, Frank Essler, Anja Behrens, Silke Lutz, Cornelia Panzner
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Abstract
A method for the production of nano- or microcapsules having a diameter of from 20 nm to 40 μm is suggested, wherein template particles are supplied in an aqueous medium, electrically recharged with a polyelectrolyte, re-recharged without separation or washing steps using a second polyelectrolyte having a complementary charge with respect to the first polyelectrolyte, and said process is optionally continued with alternately charged polyelectrolytes.
Claims31
A method for the production of nano- or microcapsules having a diameter of from 20 nm to 40 μm, characterized in that
- template particles are supplied in an aqueous medium,
- electrically recharged with a polyelectrolyte,
- re-recharged without separation or washing steps using a second polyelectrolyte having a complementary charge with respect to the first polyelectrolyte,
- said process optionally being continued with alternately charged polyelectrolytes.
The method according to any of the preceding claims, characterized in that the template particles have a size of between 20 nm and 1000 nm, preferably between 50 nm and 500 nm, and more preferably between 70 nm and 300 nm.
The method according to any of the preceding claims, characterized in that two or more dissimilar polyelectrolytes are coated simultaneously or successively in one layer.
The method according to any of the preceding claims, characterized in that a salt concentration of more than 50 mM in an aqueous solution is used.
The method according to any of the preceding claims, characterized in that the template particles are liposomes.
The method according to any of the preceding claims, characterized in that the liposomes are dissolved subsequent to coating, preferably using a detergent.
The method according to any of the preceding claims, characterized in that the liposomes have active substances entrapped therein.
The method according to any of the preceding claims, characterized in that phosphatidyl serine, phosphatidyl glycerol, phosphatidyl inositol, phosphatidic acid, sphingolipids, ceramides, tetraether lipids, cholesterol sulfate, cholesterol hemisuccinate, dimethylaminoethylcarbamoylcholesterol, alkylcarboxylic acids, alkylsulfonic acids, alkylamines, alkylammonium salts, dialkylamines, N-[1-(2,3-dioleoyloxypropyl ]-N,N,N-trimethylammonium chloride, phosphoric esters with long-chain alcohols, phosphatidyl choline, phosphatidyl ethanolamine, and/or α-tocopherol are used in the production of the liposomes.
The method according to any of the preceding claims, characterized in that coating with polymers is performed at a lipid concentration lower than 2 mM, preferably lower than 1 mM, more preferably lower than 0.5 mM, and most preferably lower than 0.2 mM.
The method according to any of the preceding claims, characterized in that liposomes including 10 to 50 mole-%, preferably 30 to 50 mole-%, more preferably 35 to 45 mole-% of charged sterols are used.
The method according to any of the preceding claims, characterized in that more than 10 mole-%, preferably more than 40 mole-%, and more preferably more than 60 mole-% of phospholipids are used.
The method according to any of the preceding claims, characterized in that the lipid membrane is present above its respective phase transition temperature.
The method according to any of the preceding claims, characterized in that the template particles are present in the form of an oil-in-water emulsion.
The method according to any of the preceding claims, characterized in that the emulsions include active substances in their oil phase.
The method according to any of the preceding claims, characterized in that natural, synthetic polymers, copolymers or block polymers comprised of at least two different monomers and/or mixed forms of these compounds are used as polyelectrolytes.
The method according to any of the preceding claims, characterized in that polysaccharides, natural or synthetic proteins, peptides, homo- or heteropolymers of amino acids, copolymers, block polymers and/or those monomers forming the basis of the synthetic polymers are used as polyelectrolytes.
The method according to any of the preceding claims, characterized in that alginic acid, chitosan, pectin, hyaluronic acid, polymannuronic acid, polygalacturonic acid, heparin, gum arabic, Indian traganth, xanthan gum, Carragheen, locust bean gum, and the salts of these compounds, as well as carboxylated, aminated, hydrazylated dextrans, starches, levans, inulins, agaroses, polyacrylic acids, polyacrylamides, polyacrylic esters, and other polymers of derivatives of acrylic acid, polyvinylpyrrolidones, polyethyleneimines, polystyrenesulfonic acids, polyallylamines, and/or polyphosphazenes are used as polyelectrolytes.
The method according to any of the preceding claims, characterized in that albumin, hemoglobin, myoglobin, antibodies, enzymes, protease, peptidase, oxidoreductase, lipase, esterase, mutase, isomerase, phospholipase, aminotransferase, acylase, lyase, hydrolase, α2-macroglobulin, fibrinogen, fibronectin, collagen, vitronectin, protein A, protein G, avidin, streptavidin, concanavalin A, and/or wheat germ agglutinin are used as polyelectrolytes.
The structures according to any of the preceding claims, characterized in that active substances are situated in the interior of said structure.
The structures according to any of the preceding claims, characterized in that the active substances are part of a coat layer.
The structures according to any of the preceding claims, characterized in that the active substances are catalysts, biocatalysts, pharmaceutical agents, proteins, oligonucleotides, nucleic acids, crystals, and/or sensor molecules.
A device for the continuous coating of liposomes with multiple polyelectrolyte layers, characterized in that a mixer (30-3X) is provided in the main flow of the liposomes effected by a pump (10), downstream of an at tenuator (20) for each separately supplied inflow of required polyelectrolyte (A-X) effected by a pump (11-1X), one timing element (41-4X) at a time being arranged between the mixers (30-3X), and one attenuator (21-2X) at a time being arranged between the pumps (11-1X) for feeding polyelectrolyte (A-X) and the mixers (30-3X).
Dependencies are inferred from the claim text.