US20040013738A1

US20040013738A1 - Encapsulation of liquid template particles

Info

Publication number: US20040013738A1
Application number: US10/343,583
Authority: US
Inventors: Andreas Voigt; Sukhorukov Gleb; Alexei Antipov; Edwin Donath; Horst Seibt
Original assignee: Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Current assignee: Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Priority date: 2000-08-02
Filing date: 2001-08-01
Publication date: 2004-01-22
Also published as: US20030175517A1; ATE273067T1; JP2004504931A; PT1305109E; CA2417792A1; ES2223914T3; EP1305109B1; EP1307282A1; US7056554B2; CA2417792C; EP1305109A1; WO2002009865A1; WO2002009864A1; DK1305109T3; DE50103245D1; WO2002009864A9

Abstract

The invention relates to a method for applying a shell to liquid template particles, comprising the following steps: (a) preparation of an emulsion of liquid template particles in a continuous liquid or gel phase, whereby at least one amphiphilic polyelectrolyte or polyelectrolyte complex, or a copolymer of charged hydrophilic monomers and oil soluble monomers is dissolved in the fluid template particles and/or the continuous phase and a film is formed at the phase boundary between the liquid template particle and the continuous phase and (b) application of a shell to the film formed at the phase boundary.

Description

DESCRIPTION

The invention concerns a method for applying a shell to liquid template particles.

DE 198 12 083.4, DE 199 07 552.2, EP 98 113 181.6 and WO 99/47252 disclose a method for producing capsules coated with a polyelectrolyte shell by applying polyelectrolytes in layers on template particles. An advantage of this method over earlier methods for producing microcapsules is that it enables the production of monodisperse capsules having a defined wall thickness. Liquid template particles can also be coated. However, since liquid template particles have a relatively low stability, the object of the invention was to provide an improved process for coating liquid template particles which at least partially eliminates the disadvantages of the prior art.

This object is achieved by a method for applying a shell to liquid template particles comprising the steps (a) providing an emulsion of liquid template particles in a continuous liquid or gel phase whereby at least one amphiphilic polyelectrolyte or polyelectrolyte complex or/and at least one copolymer of charged hydrophilic monomers and oil-soluble monomers is dissolved in the liquid template particles or/and the continuous phase thus forming a film at the phase boundary between the liquid template particle and the continuous phase and (b) applying a shell to the film formed at the phase boundary.

It was surprisingly found that the formation of a film at the phase boundary between the liquid template particle and the continuous liquid or gel phase results in a stabilization of the liquid template particle which considerably facilitates the subsequent application of a shell.

The encapsulation process according to the invention enables the encapsulation of any colloidal liquid particles e.g. emulsified oil droplets in a continuous aqueous or non-aqueous liquid phase. An oil phase is particularly preferably used as the liquid template particles and an aqueous phase e.g. a salt-containing aqueous solution in which the salt concentration is preferably between 0.001 mM and 1 M or more is particularly preferably used as the continuous liquid phase. Furthermore the process also allows the use of continuous gel phases and in particular aqueous gel phases.

An essential feature of the present invention is that a film is formed at the boundary between the template particle and continuous liquid phase. If oil droplets are used as template particles, a polyelectrolyte or polyelectrolyte complex can be used for this purpose which is soluble in the oil phase. Alternatively or in addition the polyelectrolyte or polyelectrolyte complex can also be dissolved in the continuous liquid phase e.g. an aqueous phase. Furthermore it is also possible to use surface-active copolymers which contain monomers of different polarity.

For example simplex compounds can be used as amphiphilic polyelectrolytes which contain (a) polycationic polymers and anions, for example monomeric anions such as salts of organic acids e.g. carboxylic acids or even polymeric anions such as polyacrylates or (b) polyanionic polymers and cations e.g. cationic monomers or polymers. The oleophilic behaviour of these types of compound can be influenced by the selection of the corresponding counterion for the polymer. Moreover it is also possible to use polyfunctional zwitterionic surfactants which are also amphiphilic compounds. In special cases it is possible to use combinations of polyfunctional surfactants and polyelectrolyte/counterion pairs. The concentration of the polyelectrolyte is preferably up to a maximum of 2% by weight, particularly preferably 0.01 to 1% by weight based on the total weight of the liquid template particle. Experience has shown that liquid template particles and in particular oil droplets which contain a combination of a simplex compound and a polyfunctional surfactant can be dispersed particularly well and droplets are obtained having a uniform size distribution. Furthermore the dispersions formed during the processing are more stable.

Examples of amphiphilic polyelectrolytes are simplex compounds of polycations containing ammonium ions and hydrophobic organic anions such as the salts of organic acids e.g. carboxylic acids having 10 or more carbon atoms or polyanions such as polyacrylate or polymethacrylate. Specific examples are poly(diallyl-dimethyl)ammonium stearate, palmitate, oleate or ricinolate, poly[alkyl-methyl-bis(polyoxyethylene)-ammonium]-polyacrylate or poly[alkyl-dihydroxyethyl-ethyl-ammonium]-polyacrylate where the molecular weight of the polycation is preferably ≧150,000 D and particularly preferably ≧200,000 D. Examples of suitable polyfunctional surfactants are amphiphilic polymers with cationic ammonium groups and anionic sulfinate, sulfonate, sulfate, phosphonate, phosphate or/and carboxylate groups. Specific examples of suitable surfactants are alkyl-bis(polyoxyethylene)-ammonium-sulfobetaine-sulfinate, alkyl-bis(polyoxyethylene)-ammonium-sulfobetaine-sulfonate, ethylated alkyl- or dialkyl-ammonium betaine or alkyldimethyl-ammonium-propyl-modified polysiloxanes or siloxane-sulfobetaine-sulfones.

The emulsion drops to be coated can have a size of up to 50 μm. However, the size of the drops is preferably up to 10 μm, particularly preferably 5 nm to 10 μm and most preferably 5 nm to 5 μm. The size of the drops can be adjusted by suitable treatment methods e.g. ultrasound, emulsification with a dispersing agent, extrusion or/and by adding surface-active substances to the continuous liquid phase.

The liquid template particles may be a homogeneous liquid. They can, however, also comprise a solution, an emulsion or a suspension. Furthermore the liquid template particles can consist of a liquid-crystalline substance or contain such a substance. In a preferred embodiment template particles are encapsulated which contain an active substance e.g. they themselves represent an active substance. In general active substances can be encapsulated which are dissolved or dispersed in the liquid template particle. The active substance can for example be selected from catalysts, polymers, dyes, sensor molecules, flavourings, pharmaceutical agents, herbicides, insecticides, fungicides, oils in particular pharmaceutical or cosmetic oils e.g. perfume oils or solids that are soluble in oil or can be dispersed in oil, in particular pharmaceutical active substances.

Organic liquids such as alcohols or hydrocarbons e.g. hexanol, octanol, octane or decane can also for example be encapsulated. Such capsules filled with an organic liquid that is not miscible with water can also be used for chemical reactions e.g. polymerization reactions. Hence the monomer can be concentrated specifically in the inner space of the capsules as a result of its distribution equilibrium. Optionally it is also possible to already enclose the monomer solution in the interior before the start of the synthesis.

The method according to the invention enables the production of capsules for enclosing active substances. The inner space can be loaded with molecules by varying the permeability of the shell as a function of the external physical and chemical parameters. A state of high permeability is adjusted for loading purposes. The enclosed material is subsequently retained by changing the external parameters or/and closing the pores for example by condensing the shell or by chemical or/and thermal modification of the pores or channels.

The method according to the invention allows charged or/and uncharged components to be deposited on the template particles. In a preferred embodiment of the invention the components required to form the shell contain at least one polyelectrolyte for example two oppositely charged polyelectrolytes or/and a polyvalent metal cation and a negatively charged polyelectrolyte.

Polyelectrolytes are generally understood to mean polymers having ionically dissociable groups which may be a component or substituent of the polymer chain. The number of these ionically dissociable groups in the polyelectrolytes is usually large enough to ensure the water-solubility of the polymers in a dissociated form (also referred to as polyions). The term polyelectrolyte as used herein also refers to ionomers in which the concentration of the ionic groups is not sufficient to make them water soluble, but which have sufficient charges for a self-assembly. The shell preferably contains “true” polyelectrolytes. Polyelectrolytes are divided into polyacids and polybases depending on the type of the dissociable groups. Polyanions which can be inorganic as well as organic polymers are formed from polyacids when they dissociate with cleavage of protons.

Polybases contain groups which are able to accept protons e.g. by reaction with acids to form salts. Polybases can have groups in the chains or side groups that are dissociable and form polycations by accepting protons.

Polyelectrolytes that are suitable according to the invention are biopolymers such as alginic acid, gum arabic, nucleic acids, pectins, proteins and other biopolymers that may be chemically modified such as ionic or ionizable polysaccharides e.g. carboxymethyl cellulose, chitosan and chitosan sulfate, lignin sulfonates and synthetic polymers such as polymethacrylic acid, polyvinylsulfonic acid, polyvinylphosphonic acid and polyethyleneimine.

Suitable polyanions comprise naturally occurring polyanions and synthetic polyanions. Examples of naturally occurring polyanions are alginate, carboxymethylamylose, carboxymethylcellulose, carboxymethyldextran, carageenan, cellulose sulfate, chrondroitin sulfate, chitosan sulfate, dextran sulfate, gum arabic, guar gum, gellan gum, heparin, hyaluronic acid, pectin, xanthan and proteins at an appropriate pH. Examples of synthetic polyanions are polyacrylates (salts of polyacrylic acid), anions of polyamino acids and copolymers thereof, polymaleinate, polymethacrylate, polystyrene sulfate, polystyrene sulfonate, polyvinyl phosphate, polyvinyl phosphonate, polyvinyl sulfate, polyacrylamidemethylpropane sulfonate, polylactate, poly(butanediene/maleinate), poly(ethylene/maleinate), poly(ethacrylate/acrylate) and poly(glycerylmethacrylate).

Suitable polybases comprise naturally occurring polycations and synthetic polycations. Examples of suitable naturally occurring polycations are chitosan, modified dextrans, e.g. diethylaminoethyl-modified dextrans, hydroxymethylcellulose trimethylamine, lysozyme, polylysine, protamine sulfate, hydroxyethylcellulose trimethylamine and proteins at appropriate pH values. Examples of synthetic polycations are polyallyl-amine, polyallylamine hydrochloride, polyamines, polyvinylbenzyl-trimethyl-ammonium chloride, polybrene, polydiallyldimethylammonium chloride, poly-ethyleneimine, polyimidazoline, polyvinylamine, polyvinylpyridine, poly(acryl-amide/methacryloxypropyltrimethylammonium bromide), poly(diallyldimethyl-ammonium chloride/N-isopropylacrylamide), poly(dimethylaminoethylacrylate/acrylamide), polydimethylaminoethylmethacrylate, polydimethylaminoepichlorohydrin, polyethyleneiminoepichlorohydrin, polymethacryloxyethyltrimethylammonium bromide, hydroxypropylmethacryloxyethyldimethylammonium chloride, poly(methyldiethylaminoethylmethacrylate/acrylamide), poly(methyl/guanidine), polymethylvinylpyridinium bromide, poly(vinylpyrrolidone/dimethyl-aminoethylmethacrylate) and polyvinylmethylpyridinium bromide.

Linear or branched polyelectrolytes can be used. The use of branched polyelectrolytes leads to less compact polyelectrolyte multifilms having a high degree of wall porosity. The capsule stability can be increased by cross-linking polyelectrolyte molecules within or/and between the individual layers e.g. by cross-linking amino groups with aldehydes.

It is also possible to use amphiphilic polyelectrolytes, e.g. amphiphilic block or random copolymers having a partial polyelectrolyte character. Such amphiphilic copolymers consist of units of different functionality e.g. acidic or basic units on the one hand and hydrophobic units on the other hand such as styrenes, dienes or siloxanes etc. which can be arranged as blocks or randomly distributed over the polymer. The permeability or other properties of the capsule walls can be adjusted in a defined manner by using copolymers which change their structure as a function of the external conditions. These may for example be weak polyelectrolytes, polyampholytes or copolymers having a poly(N-isopropylacrylamide) component e.g. poly(N-isopropylacrylamide acrylic acid) which due to the equilibrium of hydrogen bridges, change their water solubility as a function of the temperature which is associated with swelling.

The release of enclosed active substances can be regulated via the disintegration of the capsule walls by using polyelectrolytes that can be degraded under certain conditions e.g. photolabile, acid-labile, base-labile, salt-labile or thermolabile polyelectrolytes. Furthermore conductive polyelectrolytes or polyelectrolytes having optically active groups can be used as capsule components for special applications.

The properties and composition of the polyelectrolyte shell of the capsules according to the invention can be adjusted in a defined manner by suitable selection of the polyelectrolytes. The composition of the shells can be varied over a wide range by selection of substances for the layer structure. There are basically no limitations with regard to the polyelectrolytes or ionomers that are used provided the molecules have a sufficient charge or/and the ability to bind to the underlying layer by other types of interaction such as hydrogen bonds and/or hydrophobic interactions.

Hence suitable polyelectrolytes are low molecular polyelectrolytes or polyions and also macromolecular polyelectrolytes such as polyelectrolytes of biological origin.

The permeability of the shell wall is of particular importance for the use of the capsules. As already stated above, the large number of polyelectrolytes that are available enables the production of numerous shell compositions having different properties. In particular the electric charge of the outer shell can be adapted to the intended use. Moreover the inner shell can be adapted to the respective encapsulated active substances which can for example lead to a stabilization of the active substance. Furthermore the permeability of the shell wall can be influenced by the selection of the polyelectrolytes in the shell and by the wall thickness as well as ambient conditions. This enables a selective design of the permeability properties and a defined change in these properties.

The permeability properties of the shell can be further modified by pores in at least one of the polyelectrolyte layers. Such pores can be formed by the polyelectrolytes themselves if a suitable choice is made. In addition to the polyelectrolytes, the shell can also contain other substances in order to achieve a desired permeability. Thus the permeability to polar components can be lowered by incorporating nanoparticles having anionic or/and cationic groups or surface-active substances such as surfactants or/and lipids. The incorporation of selective transport systems such as carriers or channels in the polyelectrolyte shell and in particular in lipid layers enables an exact adaptation of the transversal transport properties of the shell to the respective intended use. The pores or channels of the shell wall can be opened or closed in a specific manner by chemical modification or/and change of the ambient conditions. Thus for example a high salt concentration of the surrounding medium leads to a high permeability of the shell wall.

A first embodiment of the method according to the invention comprises the application of polyelectrolytes in layers on the liquid template particles that have been pretreated by adding amphiphilic polyelectrolytes. The application of polyelectrolytes in layers preferably comprises several and in particular more than four process steps in which oppositely charged polyelectrolytes are successively deposited from the continuous liquid phase onto the template particle.

A second embodiment of the method according to the invention comprises a complex precipitation of multilayers or coacervation of several e.g. two oppositely charged polyelectrolytes. In this process the coating components in a complexed form are added first to the coating emulsion e.g. as complexes of two oppositely charged polyelectrolytes, and the components are transferred (redistributed) onto the boundary layer between the template particle and continuous phase by changing the media conditions. In order to carry out this process the film-forming components are for example kept in a solution e.g. in an alkaline solution in which the two are present simultaneously but without reacting with one another. The template particles to be coated are added to this solution. Subsequently it is titrated with acid, e.g. HCl, into the neutral range which results in an encapsulation of the template particles. After separation of the encapsulated particles from the complexes in the free solution e.g. by filtration, centrifugation, sedimentation (creaming) or phase separation, the template particles can be dissolved if necessary.

In a further preferred embodiment the surface precipitation can occur from a solution containing a complex consisting of a low-molecular ion and an oppositely charged polyelectrolyte. Examples of suitable low-molecular ions are metal cations, inorganic anions such as sulfate, carbonate, phosphate, nitrate etc., charged surfactants, charged lipids and charged oligomers in combination with an appropriate oppositely charged polyelectrolyte. A dispersed source for the one polyelectrolyte is generated in this process while the other polyelectrolyte is present at the same time. The polyelectrolyte of the complex can be the polycation as well as the polyanion. The choice depends on the template particles used and other conditions. In this embodiment for example a positively charged polyelectrolyte with a multiply negatively charged low-molecular anion e.g. sulfate is added to a solution of the negatively charged polyelectrolyte and a suspension of the template particles which results in a coating of the template particles. The coated template particles can for example be separated from the free complexes by centrifugation, filtration and subsequent washing and—provided they are soluble particles—be dissolved to produce microcapsules.

Another preferred embodiment comprises surface precipitation from a solution containing partially destabilized polyelectrolyte complexes (polycation/polyanion) by adding salt or/and pH variation. In this process there is a gradual transfer of polyelectrolytes from the complexes onto the template surface. This can be accomplished by introducing and stirring the negatively and positively charged polyelectrolyte in an aqueous solution having a high salt content preferably a salt content of ≧0.5 mol/l, e.g. 1 M NaCl. The template particles are coated after addition to the solution. The coated template particles can for example be isolated by centrifugation, filtration, sedimentation or other known phase separation methods and, subsequent washing and optionally dissolved to generate microcapsules.

In yet another preferred embodiment the shell comprises low-molecular cations e.g. metal cations and at least one negatively charged polyelectrolyte. Divalent cations and in particular trivalent cations are for example used as cations. Examples of suitable cations are alkaline earth metal cations, transition metal cations and rare earth element cations such as Ca ²⁺, Mg²⁺, Y³⁺, Tb³⁺ and Fe³⁺. On the other hand it is also possible to use monovalent cations such as Ag⁺. Template particles coated with a metal layer can be produced by reducing the metal cations.

In yet another preferred embodiment the components that are necessary to form the shell comprise at least one macromolecule e.g. an abiogenic macromolecule such as an organic polymer or a biomolecule such as a nucleic acid e.g. DNA, RNA or a nucleic acid analogue, a polypeptide, a glycoprotein or a polysaccharide having a molecular weight of preferably ≧5 kD, and particularly preferably of ≧10 kD. The macromolecules can carry charges such as nucleic acids or be uncharged such as polysaccharides e.g. dextran. The macromolecules can optionally be combined with polyelectrolytes or/and polyvalent metal cations in which case combinations of macromolecular and low-molecular biological cell substances, macromolecular and low-molecular abiogenic substances and macromolecular and biogenic and abiogenic substances can for example be used.

In yet a further preferred embodiment the components that are added to form the shell comprise a mixture of several polyelectrolytes or/and lipids or/and proteins or/and peptides or/and nucleic acids or/and other organic and inorganic compounds of biogenic or abiogenic origin. A suitable composition of the liquid continuous phase with regard to salt content, pH value, cosolvents, surfactants and a suitable selection of the coating conditions e.g. temperature, rheological conditions, presence of electrical or/and magnetic fields, presence of light etc. results in a self-assembly of the diverse shell components on the templates to form complex structures having a wide variety of biomimetic properties.

The application according to step (b) of the method according to the invention occurs under conditions such that a shell of a defined thickness is formed around the template which is in the range of 1 to 100 nm, preferably 1 to 50 nm, particularly preferably 5 to 30 nm and most preferably 10 to 20 nm. When applied in layers, the wall thickness and the homogeneity of the capsule shell are determined by the number and composition of the layers and by the precipitation process, which essentially depends on the concentration of the template particles, the concentration of the coating components and the rate of the solubility change in the liquid phase which causes the precipitation.

An application by means of precipitation can for example be carried out by firstly adding a part of the components forming the shell to the liquid phase and subsequently adding one or more additional shell components. Such a precipitation step can for example be used for a combination of metal cations and oppositely charged polyelectrolytes. Another method of precipitation is that the components required to form the shell are already completely present in the liquid phase and a change in the liquid phase occurs which results in the precipitation. This change in the liquid phase can for example comprise a change of the pH value and/or a change in the composition of the liquid phase e.g. by adding a solvent component or/and removing a solvent component. Thus for example hydrophilic biopolymers such as DNA or polysaccharides can be precipitated by adding ethanol to an aqueous liquid phase, whereas polyelectrolyte combinations can be precipitated by evaporating off an organic solvent such as acetone from the liquid phase.

The components used to form the shell can alternatively or in addition also comprise nanoparticles e.g. organic or inorganic nanoparticles, in particular nanoparticles having electrical, magnetic or optical properties e.g. magnetite or CdTe.

The coating method according to the invention can additionally comprise at least one additional coating step before or/and after the precipitation step. Such an additional coating step can for example comprise the application of one or more lipid layers or/and the application of layers of polyelectrolytes.

The permeability of a shell can be modified by depositing lipid layers or/and amphiphilic polyelectrolytes on the polyelectrolyte shell. This can result in a very substantial reduction of the permeability of the shells to small and polar molecules. Examples of lipids that can be deposited on the shells are lipids which carry at least one ionic or ionogenic group e.g. phospholipids such as dipalmitoylphosphatidic acid or zwitterionic phospholipids such as dipalmitoylphosphatidyl choline or fatty acids or corresponding long chain alkylsulfonic acids. The use of zwitterionic lipids enables the deposition of lipid multilayers on the shell.

The application of polyelectrolytes in layers can for example be carried out as described in WO 99/47252. The layered assembly of the shells can for example be combined with the precipitation step according to the invention in such a manner that firstly a small number e.g. 1 to 4 layers of polyelectrolytes are layered onto the template particles which is followed by a precipitation step. Alternatively or additionally it is also possible to deposit layers of polyelectrolytes on the shell after the precipitation steps. A chemical reaction can also occur in or/and on the shells.

The method according to the invention allows the production of capsules whose size distribution corresponds to that of emulsions and which in contrast to surfactant-stabilized systems, exhibit no change in their size distribution in the sense of an Ostwald maturation. The capsules are very stable towards chemical, biological, mechanical and thermal stress. If they have a suitable composition they can be dried and resuspended. They can be stored as a concentrate in aqueous or aqueous-gel like phases.

The invention is further elucidated by the following figures and examples. [0040]
FIG. 1 shows an embodiment of the method according to the invention comprising a one step formation of a polyelectrolyte/ion shell on colloidal liquid template particles. [0041]
FIG. 2 shows another embodiment of the method according to the invention comprising a self-assembly of polymer films on the surface of colloidal liquid particles.[0042]
FIGS. 1 and 2 show a schematic representation of two embodiments of the method according to the invention. In FIG. 1 a suspension of liquid template particles with added amphiphilic polyelectrolytes ([0043] 2) is produced which contains metal ions e.g. ions of a polyvalent metal or ions of a noble metal such as Ag⁺ (4). An ion/polyelectrolyte shell is precipitated on the template particles by dropwise addition of a solution containing negatively charged polyelectrolyte molecules (6). The coated template particles (8) can be further processed in various ways. Thus empty capsules (10) can be produced by dissolution of the template particles. Metal-coated capsules (12) are obtained by reducing the metal ions. By applying layers of oppositely charged polyelectrolytes (14 a, 14 b) it is possible to produce capsules with an anisotropic shell in which case the inner part is an ion/polyclectrolyte shell and the outer part is a polyelectrolyte/polyelectrolyte shell assembled in layers. Empty capsules (18) can be subsequently produced by dissolving the template particles. The inner ion/polyelectrolyte part of the shell can be dissolved by removing the metal ions (4) such that the polymer (6) is encapsulated in the interior of the shell formed (20) by the oppositely charged polyelectrolytes (14 a, 14 b).
Another embodiment of the method according to the invention is shown in FIG. 2. A suspension of colloidal liquid template particles with added amphiphilic polyelectrolytes ([0044] 32) is placed in a liquid phase which contains a polymer e.g. a nucleic acid, a protein, a polysaccharide or a synthetic polymer in a dissolved form. The polymer is precipitated to form template particles (36) coated with the polymer by changing the solvent composition e.g. by the dropwise addition of ethanol or another solvent in which the polymer is insoluble or only poorly soluble. Deposition of layers of oppositely charged polyelectrolytes (38 a, 38 b) allows the production of coated template particles with an anisotropic shell (40) where the inner section of the shell is formed by the precipitated polymer and the outer section is formed by layers of oppositely charged polyelectrolytes. If soluble template particles are used it is possible to dissolve them to form a polymer (42) encapsulated in the polyelectrolyte/polyelectrolyte shell.

EXAMPLES

Example 1

Preparation of Droplet Emulsions Stabilized by Amphiphilic Polyelectrolytes [0045]
1.1 [0046]
0.1 g of a mixture of hexadecyl/octadecyl-bis(polyoxyethylene)-3-sulfopropyl-ammonium-betaine and sodium hexadecyl/octadecyl-bis(polyoxyethylene)-2-sulfinato-3-sulfopropyl-ammonium-betaine and poly(diallyldimethyl)ammonium-stearate (weight ratio of simplex compound to polyfunctional surfactant 2:1) is dissolved in 10 g oil. [0047]
1.2 [0048]
0.05 g of a mixture composed of hexadecyl/octadecyl-bis(polyoxyethylene)-3-sulfopropyl-ammonium-betaine and sodium hexadecyl/octadecyl-bis(polyoxyethylene)-2-sulfinato-3-sulfopropyl-ammonium-betaine and poly[alkylmethyl-bis(polyoxyethylene)-ammonium]-polyacrylate (weight ratio of simplex compound to polyfunctional surfactant 2:1) is dissolved in 10 g oil. [0049]
1.3 [0050]
0.05 g poly(diallyldimethyl)ammonium-poly(stearate) or poly(diallyldimethyl)-ammonium-poly(erucic acid) is dissolved in 10 g oil. [0051]
1.4 [0052]
0.05 g alkyl-dimethyl-ammonium-propyl-modified polycationic polysiloxane is dissolved in 10 g oil. [0053]
1.5 [0054]
0.02 g of a mixture of hexadecyl/octadecyl-bis(polyoxyethylene)-3-sulfopropyl-ammonium-betaine and sodium-hexadecyl/octadecyl-bis(polyoxyethylene)-2-sulfinato-3-sulfopropyl-ammonium-betaine is dissolved in 10 g oil. [0055]

Example 2

Layered Assembly of Polyelectrolyte Multilayers on Oil Droplets [0056]
The modified oil phase according to the instructions 1.1 to 1.5 is emulsified in aqueous solutions of suitable polyelectrolytes. The process is preferably continued using a polyanion in the aqueous phase in the case of 1.1, 1.3 and 1.4 and a polycation in the aqueous phase in the case of 1.2. 1.5 can be processed further in polycationic as well as in polyanionic systems. The resulting polyelectrolyte complexes in the oil/water phase boundary give the emulsion the necessary temporary stability towards coalescence and also stabilize the phase boundary itself so that it is possible to continue using known stepwise or one-step processes for the generation of polyelectrolyte multilayers. [0057]
1 ml oil (unmodified or modified with an amphiphilic polyelectrolyte as described in example 1.1 or 1.3) is emulsified with 5 ml poly(styrenesulfonate sodium salt) (PSS) having a molecular weight of 70,000 D from Aldrich (1 mg/ml in 0.5 M NaCl) by means of ultrasound e.g. with an Ultraturrax. This results in the formation of a first polyelectrolyte double layer at the phase boundary between the emulsion droplets and the continuous aqueous phase. [0058]
Subsequently 10 ml poly(allylamine hydrochloride) (PAH) having a molecular weight of 50 to 65,000 D from Aldrich (1 mg/ml in 0.5 M NaCl) is admixed while shaking to generate a second layer. The third layer is formed by adding 15 ml PSS and the fourth layer is formed by adding 20 ml PAH. A total of up to 10 layers (tenth layer 50 ml PAH) are formed in this manner. [0059]
Multiple washing in a separating funnel results in stable emulsions. This can be optionally followed by cross-linking steps e.g. by glutardialdehyde. [0060]

Example 3

Complex Precipitation or Coacervation from Alkaline PSS/PAH Solution using Emulsion Droplets as the Template [0061]
An initial solution of the two polyelectrolytes is prepared in which they are both present simultaneously in solution without reacting with one another. This is achieved by firstly adding 100 ml 0.1% (w/w) NaOH solution containing 0.1 M NaCl. 300 mg PSS (MW 70,000) and 200 mg PAH (MW 50-65,000) are successively dissolved in this solution. It is shaken until complete dissolution. This solution is stable for several hours. 20 ml oil (unmodified or modified according to formulations 1.1 to 1.5) is added. It is subsequently emulsified with an Ultraturrax and then rapidly titrated into the neutral range with 10% (w/w) HCl. The emulsion is subsequently purified e.g. washed several times in a separation funnel. This results in an emulsion which is stable for months. [0062]

Example 4

One-Step Precipitation from a Solution Containing a Complex of a Polyelectrolyte and a Multivalent Ion [0063]
Solution I: 1 ml PSS solution (2 mg/ml) is mixed with 200 μl of a Y(NO[0064] ₃)₃solution (2×10⁻²M). The resulting charge ratio between sulfate and yttrium is 5:3.
Solution II: 400 μl oil is mixed with 1 ml water. The mixture is emulsified for 3 to 4 minutes with ultrasound in an Ultraturrax. [0065]
Solution I is then rapidly added to solution II and the resulting emulsion is shaken in a vortex for 2 minutes. The emulsion is stable for more than 20 hours and can optionally be used as a starting system for further coatings. [0066]

Claims

1. Method for applying a shell to liquid template particles comprising the steps:

(a) providing an emulsion of liquid template particles in a continuous liquid or gel phase whereby at least one amphiphilic polyelectrolyte or polyelectrolyte complex or a copolymer of charged hydrophilic monomers and oil-soluble monomers is dissolved in the liquid template particles or/and the continuous phase thus forming a film at the phase boundary between the liquid template particle and the continuous phase and

(b) applying a shell to the film formed at the phase boundary.

2. Method as claimed in claim 1,

characterized in that,

an oil phase is used as the liquid template particle and an aqueous or an aqueous-gel-like phase is used as the continuous phase.

3. Method as claimed in claim 1 or 2,

characterized in that,

the liquid template particles are selected from particles having a diameter of up to 50 μm, in particular up to 10 μm.

4. Method as claimed in one of the claims 1 to 3,

characterized in that,

the liquid template particles comprise a solution, an emulsion or a suspension.

5. Method as claimed in one of the claims 1 to 4,

characterized in that,

the liquid template particles are composed of a liquid-crystalline substance or contain such a substance.

6. Method as claimed in one of the claims 1 to 5,

characterized in that,

the template particles contain an active substance.

7. Method as claimed in claim 6,

characterized in that,

the active substance is selected from catalysts, polymers, dyes, sensor molecules, flavourings, drugs, herbicides, insecticides, fungicides.

8. Method as claimed in claim 6 or 7,

characterized in that,

the active substance is selected from oils, in particular perfume oils, pharmaceutical oils and active pharmaceutical substances dissolved or dispersed in oil.

9. Method as claimed in one of the claims 1 to 8,

characterized in that,

the amphiphilic polyelectrolyte contains simplex compounds of polycationic polymers and anions.

10. Method as claimed in one of the claims 1 to 8,

characterized in that,

the amphiphilic polyelectrolyte contains simplex compounds of polyanionic polymers and cations.

11. Method as claimed in one of the claims 1 to 8,

characterized in that,

the amphiphilic polyelectrolyte contains polyfunctional zwitterionic surfactants.

12. Method as claimed in one of the previous claims,

characterized in that,

the amphiphilic polyelectrolyte is used in an amount of up to 2% by weight based on the weight of the template particles.

13. Method as claimed in one of the previous claims,

characterized in that,

the application of the shell comprises a layered assembly or/and a precipitation of multilayers or/and a coacervation from the continuous liquid phase.

14. Method as claimed in one of the previous claims,

characterized in that,

the components used to form the shell comprise at least one polyelectrolyte.

15. Method as claimed in claim 14,

characterized in that,

the components used to form the shell comprise two oppositely charged polyelectrolytes.

16. Method as claimed in claim 15,

characterized in that,

the components used to form the shell comprise a polyvalent low-molecular cation and a negatively charged polyelectrolyte or a polyvalent low-molecular anion and a positively charged polyelectrolyte.

17. Method as claimed in one of the previous claims,

characterized in that,

the film-forming components are placed first in a complexed form in the coating emulsion and the components are transferred onto the boundary layer between the template particle and the continuous phase by changing the media conditions.

18. Method as claimed in one of the previous claims,

characterized in that,

the components required to form the shell comprise at least one macromolecule.

19. Method as claimed in claim 18,

characterized in that,

a biopolymer, an abiogenic polymer or a mixture thereof optionally in combination with low-molecular biogenic or/and abiogenic substances is used.

20. Method as claimed in one of the previous claims,

characterized in that,

nanoparticles having electrical, magnetic or optical properties are used to form the shell.

21. Method as claimed in one of the previous claims further comprising the disintegration of the liquid template particles.

22. Method as claimed in one of the previous claims further comprising on at least partial disintegration of the shell.

23. Method as claimed in one of the previous claims,

characterized in that,

a shell having a thickness of 1 to 100 nm is formed around the template particles.

24. Method as claimed in one of the previous claims,

characterized in that,

a shell having a thickness of 1 to 50 nm is formed around the template particles.

25. Method as claimed in one of the previous claims,

characterized in that,

a chemical reaction is carried out in or/and on the shells.