WO2009091255A1

WO2009091255A1 - Hollow structures with a shell of colloidal particles

Info

Publication number: WO2009091255A1
Application number: PCT/NL2009/050019
Authority: WO
Inventors: Albert Thijs Poortinga
Original assignee: Friesland Brands B.V.
Priority date: 2008-01-18
Filing date: 2009-01-16
Publication date: 2009-07-23
Also published as: NL2001199C2; EP2244587A1

Abstract

The invention relates to a method of preparing a hollow body, comprising preparing a suspension comprising an aqueous discontinuous phase, an aqueous continuous phase and colloidal particles, and aggregating colloidal particles at an interface between continuous and discontinuous phase, thereby forming the hollow body. The invention further relates to a hollow body obtainable by means of the method.

Description

Title: Hollow structures with a shell of colloidal particles

The invention relates to a method of preparing a hollow body, for instance a microcapsule or a tubular structure. The invention also relates to a hollow body.

Hollow bodies, such as microcapsules, are used in many fields. Thus, for instance, particles of an active substance, such as a medicine or a nutrient, may be surrounded by a protective layer (as by means of encapsulation) to protect the active substance from undesired effects of the environment and/or to protect the environment from the active substance.

A special form of hollow bodies are so-called colloidosomes, bodies which contain a shell which is built up from colloidal particles, which shell encloses an internal phase, for instance a liquid phase containing an active substance.

In WO 02/47665, the preparation of colloidosomes is described with the aid of an emulsion of the water-in-oil type or the oil-in -water type. To obtain water-filled colloidosomes, colloidal particles are dissolved in a hydrophobic continuous phase (such as toluene), after which water is added as a discontinuous phase. The examples all use a synthetic polymer, such as polystyrene or polymethyl methacrylate. After allowing aggregation of the particles, if desired, the hydrophobic continuous phase may be replaced by water after the colloidosomes have been formed. Here, the colloidosomes need to be prevented from breaking as a result of the great forces exerted on the colloidosomes, for instance as a result of the surface tension. To this end, the colloidosomes are washed first with octanol and then added to an aqueous solution of a surface-active substance. To keep the colloidosomes intact, the particles are usually strongly bonded to one another, for instance by sintering.

It is an object of the invention to provide a new method of preparing a hollow body, such as a capsule or a tubular body. It is particularly an object of the invention to provide a new method of preparing hollow bodies, which comprise an aqueous phase at least substantially surrounded by a shell, which bodies are suspended in an aqueous phase, which method is less laborious than the above-mentioned method.

It is further an object to provide new hollow bodies, in particular hollow bodies also suitable for use in a foodstuff and/or for a medical use.

One or more other objects which can be realized by means of the invention follow from the description hereinafter. It has now been found that one or more objects can be realized by preparing hollow bodies in a specific manner.

Therefore, the present invention relates to a method of preparing a hollow body, comprising preparing a suspension comprising an aqueous discontinuous phase, an aqueous continuous phase and colloidal particles, and aggregating colloidal particles at an interface between continuous and discontinuous phase, thereby forming the hollow body.

A hollow body (formed by means of a method) according to the invention is hence a body comprising a cavity, which cavity is at least partly filled with an aqueous phase. The aggregated particles form a surrounding phase. Typically, a hollow body according to the invention has one space (cavity), in which aqueous phase is present which is surrounded by a surrounding phase. Such bodies are also referred to as bodies with a liquid core-shell morphology. In a preferred embodiment, the space is at least substantially spherical or at least substantially tubular. Typically, the thickness of the surrounding phase is smaller than the diameter of the space in which the aqueous phase is present.

A method according to the invention is particularly suitable for manufacturing a hollow body with a particular shape, with a particular composition of the surrounding phase (shell) of the body which surrounds a space (cavity) which contains an aqueous phase, and/or particular properties, such as permeability, mechanical strength and/or elasticity of the shell.

In one embodiment, the invention relates to a hollow body, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid, while the surrounding phase comprises at least one component chosen from the group of triglycerides, proteins, prokaryotic cells, eukaryotic cells, monoglycerides and diglycerides. In one embodiment, the invention relates to a hollow body, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, while the structure is at least substantially tubular.

In one embodiment, the invention relates to a hollow body, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid, while the surrounding phase is at least substantially free of macropores (pores with a diameter larger than 50 nm), preferably at least substantially free of macropores and of mesopores (pores with a diameter in the range of 2-50 nm). In one embodiment, the invention relates to a hollow body suitable for use in a foodstuff, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid.

Surprisingly, it has been found possible, without needing to use a multiphase liquid system of a hydrophilic phase and a hydrophobic phase, to make hollow bodies with a shell which is at least substantially formed from colloidal particles, which particles may optionally be merged wholly or partly. This is advantageous with respect to the simplicity with which the particles can be prepared, i.e. if desired without using an organic liquid to be removed later. Because, during a method according to the invention, use can exclusively be made of aqueous liquid phases, generally, smaller forces are exerted on the hollow bodies than in a method where a multiphase system is used which comprises an aqueous phase (or at least a hydrophilic phase) and an organic phase (hydrophobic phase). As a result, the chance of the bodies breaking during preparation is lower (under otherwise equal conditions) and/or the shell of colloidal particles needs to have only a relatively small strength. This means that use can be made of a wider range of particles, including, for instance, fat particles (hollow particles in which the surrounding phase consists at least substantially of fat), particles in which the surrounding phase comprises aggregated cells of a microorganism, and a wider range of manners to aggregate the particles, for instance using rather weak forces.

"At least substantially" is generally understood to mean for more than 50% up to maximally 100%, in particular for at least 75%, more in particular for at least 90%. "At least substantially surrounded" is in particular understood to mean: for 90%- 100% of the surface, more in particular for at least 95%, as at least 99% of the surface.

Herein, "an aqueous phase" is understood to mean water or a liquid which consists at least substantially of water, i.e. for more than 50 to 100 wt.%, in particular for at least 75 wt.%, more in particular for at least 95 wt.%, such as for at least 99 wt.%. The remainder of the liquid typically comprises one or more water-miscible solvents such as one or more solvents chosen from the group of water-miscible ketones (for instance acetone) and water-miscible alcohols, in particular methanol, ethanol, propanol, glycerol, including mixtures thereof.

As a method according to the invention can be carried out under mild conditions, for instance without using a (hydrophobic) organic solvent and/or without needing to heat or cool, the invention also offers the possibility to prepare bodies with a surrounding phase of a material which is sensitive to extreme conditions, for instance in that it is not resistant to or at least is adversely affected by a (hydrophobic) organic solvent or an extreme temperature. Mild conditions also offer the possibility to encapsulate one or more active components (which may be present in the discontinuous phase), which are, for instance, heat-sensitive or which are adversely affected by a (hydrophobic) organic solvent.

The invention is particularly suitable for preparing bodies with a core-shell morphology, with the discontinuous phase as a core and the surrounding phase as a shell. The shell comprises preferably maximally 50% of the volume of the body, more preferably maximally 10% of the volume of the body, for instance at least 0.1%, at least 0.5% or at least 1.0% of the volume of the body.

The inventors have also found that a method according to the invention is eminently suitable for preparing bodies with a non-spherical shape. It has been found that, for instance, tubular structures can be made in the continuous phase which are sufficiently stable to bring about aggregation of colloidal particles at the interface (while the structure is fixed), before the structures have sufficient time to relax into a spherical structure or to break down into smaller spherical drops. If desired, after manufacture of the tubular structure, liquid phase can be removed from the structure.

The particle size of the colloidal particles may be chosen within wide limits, depending on factors such as a desired layer thickness, porosity, and the like. Typically, the surface-average particle size, determinable by means of light scattering, is at least 0.05 μm, in particular at least 0.1 μm. The upper limit depends on the desired shell thickness and is typically maximally some tens of μm, for instance maximally 50 μm, in particular maximally 10 μm, more in particular maximally 5 μm.

The colloidal particles may particularly contain one or more of the following components: triglycerides, in particular triglycerides which are at least substantially solid at 20⁰C (fats), diglycerides, monoglyce rides; prokaryotic cells, in particular probiotic bacteria, such as Lactobacilli or Bifidobacteria; eukaryotic cells, for instance endothelial cells; proteins, such as milk proteins, in particular whey protein or casein; carbohydrates, and inorganic oxide particles, in particular (poorly water-soluble) calcium salts or quartz. If desired, the particles may be provided with an agent which affects the hydrophilicity or hydrophobicity of the particles or with an agent which facilitates aggregation of the particles. The colloidal particles are typically form-retaining at 20⁰C (i.e. not liquid), for instance in a solid state or gelled. If the particles electrostatically repel one another, a suitable counterion may be added to bring about or facilitate aggregation. For instance in the case of particles which contain a casemate (for instance caseinate-stabilized fat-containing particles), calcium may be added to allow the particles to aggregate. Preferably, the colloidal particles are suitable for use in a foodstuff or a medical use.

The preparation of the suspension is based on the principle that aqueous solutions of two or more types of polymers or of a polymer and a particular other additive (polymer/additive A and polymer/additive B, respectively) can separate when the above-mentioned additives are present in a particular concentration. This creates at least two phases, polymer/additive A mainly ending up in one phase and polymer/additive B in the other. In this manner, an emulsion can be created in which one phase is dispersed as small drops in the other phase. The continuous and the dispersed phase then contain at least substantially the same liquid; the driving force behind the maintenance of the emulsion are the polymers or the polymer and the other separating additive. In the case where water is the solvent, this is referred to as a water-in-water emulsion.

Suitable combinations of additives A and B which can separate are known per se, see for instance Y. Guan et al. in Pure & Appli. Chem., vol. 67, No 6, pp. 955-962 (1995), in which use of various combinations of separating polymers and combinations of a polymer and salt is described to obtain a two-phase aqueous system.

Through the invention, it has surprisingly been found possible to choose conditions such that colloidal particles, which at least substantially do not dissolve in the continuous phase and do not dissolve in the discontinuous phase, aggregate preferentially at or near the interface between the continuous and the discontinuous phase. This can be determined empirically on the basis of general knowledge in the art and what is described herein.

The suspension is typically prepared at or around ambient temperature, as at a temperature in the range of 10-35°C, more particularly in the range of 15-30⁰C, although the preparation of the suspension may in principle take place at a temperature outside this range. Additive A and additive B are different from each other. In particular, additive A and/or B may be chosen from biopolymers, in particular from the group of polypeptides, including proteins, and polysaccharides, including derivatives thereof. More in particular, additive A and/or B may be chosen from the group of whey proteins (such as beta- lactoglobulins, alpha-lactalbumin, immunoglobulins), casein, chicken protein, soy protein, lupine bean protein, coconut protein, dextran (in particular underivatized dextran), caseinate, alginate, maltodextrin, starch, pectin, cellulose, gum arabic, carob flour, carrageenan, fenugreek gum, guar gum, tara gum, cassia gum. Suitable derivatives comprise in particular alkyl cellulose, more in particular methylcellulose, and alkoxy pectins, for instance methoxy pectin.

The additives A and B may be of a different or the same class. Examples of different classes are in particular the class of polypeptides, including proteins, and the class of polysaccharides. Good results have been obtained with a method where additives A and B are of the same class, for instance both of the class of polysaccharides. Particularly suitable is a combination of a dextran and an alkyl cellulose, such as methylcellulose; a combination of a maltodextrin and an alkyl cellulose, such as methylcellulose; a combination of a dextran and a maltodextrin; or a combination of a maltodextrin and an alkyl cellulose. Of such a combination, it has been found that, for instance, fat particles, monoglyceride particles, silica particles (quartz particles), protein particles (whey protein), or probiotics concentrate at the interface between the two aqueous phases. Depending on the amounts of the two additives, the additive may end up at least substantially in the continuous phase or at least substantially in the discontinuous phase.

At least if it is desired to fix the additive for the discontinuous phase, at least the polymer for the first phase (polymer A) is preferably cross-linkable. Particular polymers, such as sulfur-containing proteins, can be cross-linked by means of heating (with sulfur bridges providing cross- linkage), such as, for instance, whey proteins such as beta-lactoglobulin and alpha-lactalbumin, soy protein and chicken protein.

Particular carbohydrates, such as alginates, pectins, and the like, can be cross-linked by addition of cations such as calcium. A number of polymers can be cross-linked by acidification or under the influence of an enzyme. An enzyme such as a transglutaminase, for instance, is very suitable to cross-link a protein under mild conditions. Chemical cross- linking reactions (by reaction with a cross-linking agent) are also possible. In an embodiment in which additive A is fixed, the additive which is at least substantially intended for the continuous phase (additive B) is preferably chosen such that, at least under the conditions in which the additive A for the discontinuous phase is fixed if desired, it is at least substantially not fixed.

The volume ratio of the continuous phase to the discontinuous phase may be chosen within wide limits; typically the volume of the continuous phase is at least approximately as large as that of the discontinuous phase, although it may be lower in at least a number of embodiments. The ratio of continuous phase to discontinuous phase may, for instance, be at least 40:60, in particular at least 50:50, at least 70:30 or at least 80:20. The ratio of continuous phase to discontinuous phase is typically maximally 99:1, in particular maximally 95:5, more in particular maximally 90:10 or maximally 80:20.

Suitable concentrations for additive A and additive B can be determined empirically depending on the chosen polymers. Very suitable for the preparation of the emulsion is a method in which a solution is prepared which contains polymer A and a solution which contains polymer B or other separating additive B. Then both solutions are combined, after which separation occurs, thereby forming the emulsion. A particularly suitable manner of combining the solutions is injecting one solution into the other solution.

Preferably, a solution is prepared of additive A and a solution of additive B, while the solvents in the above-mentioned solutions are the same or are, at least in absence of the polymers A and B, soluble into each other or completely miscible at the temperature at which the suspension is prepared.

The concentrations of the additives A and B are preferably chosen such that, upon aggregation of the colloidal particles, the solvents remain separated, while the weight concentration of the additive A (CA) is higher and the weight concentration of the additive B (CB) is lower than the respective concentrations in the continuous phase.

As a rule, a concentration, based on weight, is suitable which is such that CA in the first phase is 2-50 times higher than in the continuous phase and/or CB in the first phase is 2-50 times lower than in the continuous phase. Thus, it is possible to prepare a multiphase system where there is no or hardly any exchange of additives A and B between the different phases. Optionally, the value of the pH may be set to facilitate the phase separation. It may particularly be advantageous when a polypeptide or another amphoteric polymer is used to set the pH at a value around the isoelectric point of the amphoteric polymer. At least in a number of embodiments, conditions may be chosen such that aggregation occurs spontaneously. For instance in a method in which a two-phase system is used with a phase of dextran dissolved in water and a phase of methylcellulose dissolved in water, particles consisting of fat (for instance milk fat particles) can aggregate at room temperature, without an aggregation-promoting agent needing to be added.

Aggregation of the colloidal particles, thereby forming an envelope around at least a part of the discontinuous phase, can be brought about with the aid of an aggregation-promoting agent. Suitable aggregation-promoting agents for a particular type of particle are known per se. In one embodiment, colloidal particles, for instance protein- containing particles, such as protein-containing fat particles, are aggregated with the aid of a calcium salt, such as calcium chloride. The protein may, for instance, be a casemate. Such a protein may, for instance, be present on the particle surface, while the protein serves to stabilize the dispersion of the particles (prior to aggregation).

In one embodiment, colloidal particles, for instance fat particles or protein-containing particles, are aggregated with the aid of a pH decrease by adding an acid, such as glucono-δ-lactate.

Other agents which are, at least in a number of embodiments, suitable to bring about or promote aggregation are, for instance, ethanol or polymers which lead to so-called depletion flocculation.

For particles with a surface charge, a method in which aggregation takes place with the aid of complex coacervation is very suitable. This may, for instance, be done by adding alginate or another charged polymer to the suspension under pH conditions in which the added polymer has a charge opposite to the charge of the colloidal particles. In the case of adding alginate to a neutral suspension which contains, for instance, fat particles or protein-containing particles, decrease of the pH, with the aid of an acid, such as glucono-δ-lactate, will lead to aggregation of the particles in that the oppositely charged alginate adsorbs on the particles adjoining one another so that they 'stick' together.

Typically, an aggregation-promoting agent is added such that the liquid phase does not gel. Usually, the aggregating agent is added slowly, or an agent is used which allows the aggregation to take place with some delay, so that aggregation and mixing do not take place at the same time because this can cause damaging of the hollow bodies. Glucono-δ-lactate is an example of such an aggregating agent. Gradually bringing the suspension under a CO2 pressure is also a possibility to make aggregation take place slowly in an embodiment in which aggregation is promoted by a pH decrease.

After aggregation, the bodies may be separated from the continuous phase if desired, without the colloidal particles needing to be bound chemically (for instance cross-linked) or coalesced by means of sintering, although, in principle, this is possible. Suitable separation methods are known per se. Possibilities are, for instance, filtering, decanting and spray-drying.

Surprisingly, after aggregation, it is possible to dilute the bodies with an aqueous liquid such that the phase-separating additives A and B would dissolve in a single phase again, while the bodies remain at least substantially intact, despite the development of interface tensions during such a dilution.

At least in a number of embodiments, the aggregation of the colloidal particles is reversible. For instance, in an embodiment in which use has been made of aggregation with the aid of a metal ion, such as calcium, the aggregation can be brought about by a chelating agent for the metal ion, for instance EDTA. In an embodiment in which aggregates have been formed under the influence of an acid, an increase of the pH, for instance to pH 10, may lead to destabilization of the aggregates. Such a property may be desired for bringing about a controlled release. The morphology of the bodies may be at least substantially ball-shaped (spherical or ellipsoidal) or at least substantially tubular. For the preparation of an essentially spherical body, it is suspected that it is desirable to use colloidal particles with a high degree of monodispersity, to stir or otherwise move the reaction mixture only carefully or not at all, and/or to use a discontinuous phase which is at least partly gelled or is at least more viscous than the continuous phase. By applying a particular shearing rate to the phase-separated suspension, the bodies can obtain a more elongated character, so that more ellipsoidal bodies or even at least substantially tubular bodies are formed. Obtaining tubular bodies can be facilitated by choosing a more viscous disperse phase (discontinuous phase).

The invention also relates to a hollow body, in particular a hollow body obtainable by means of a method according to the invention. A hollow body according to the invention comprises a surrounding phase (shell) which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid.

The dimension of the body may be chosen within wide limits. The body may in particular be a hollow microparticle. Typically, the number- average diameter of the bodies as determinable by means of microscopy is at least 1 μm, preferably at least 5 μm. The number-average diameter is preferably maximally 100 μm, in particular maximally 50 μm.

The layer thickness of the shell is partly determined by the size of the colloidal particles and the average number of layers in which the particles accumulate at the interface, during the preparation. Typically, the layer thickness of the shell is at least 0.1 μm, in particular at least 0.2 μm. Typically, the layer thickness of the shell is maximally 10 μm, preferably maximally 5 μm.

By means of the invention, it is possible to provide a body with a porous or a non-porous surrounding phase. A porous shell may comprise micropores, mesopores and/or macropores. A low porosity may, for instance, be brought about by allowing colloidal particles, for instance fat-containing particles, to merge (coalesce) after or during the aggregation, by using polydisperse colloidal particle compositions, where relatively small particles (partly) fill the interstitial space between relatively large particles or by the use of a sealing agent.

If desired, the body may contain an active substance, for instance a nutrient or a medicine. This substance can be dissolved in the liquid for the discontinuous phase, prior to the preparation of the particles, or the particles (if sufficiently permeable to the active substance) can have been loaded with the particles at a later stage, for instance with the aid of a diffusion process.

After consumption, the active substance can be released at a controlled rate, for instance in the gastrointestinal tract. The release rate can be set on the basis of porosity and degradation rate of the surrounding phase in the gastrointestinal tract. The degradation rate may be affected by, for instance, the nature of the colloidal particles.

In one embodiment, the surrounding phase of the hollow bodies consists at least substantially of one or more triglycerides, preferably substantially of fat. Such bodies, particularly hollow microparticles with a triglyceride -containing surrounding phase, are, for instance, suitable as a fat substitute in a foodstuff. These particles can provide the foodstuff with a full-cream impression in that they have an outer surface consisting at least substantially of triglyceride, while they only contribute to the actual fat content for a limited part in that the cores of the particles are substantially fat-free (i.e. contain an aqueous phase). Bodies by means of the invention may be essentially spherical or ellipsoidal.

In one embodiment, a body according to the invention has an elongated geometry, for instance an essentially tubular geometry. Such a body could, for instance, be used as a (thin) filter membrane or in the production of a blood vessel, for instance by using endothelial cells as colloidal particles. In a special embodiment, such a body has an internal diameter in the range of 1-100 μm, more in particular of 1-50 μm or of 1-10 μm. The invention will now be explained in and by a number of examples.

Example 1

10 vol.% of a 20 wt.% dextran solution (D5376, Sigma-Aldrich, MW about 2,000,000 g/mol) in water was added to 90 vol.% of a 4 wt.% methylcellulose solution (Methocel A15LV, AKZO-Nobel) in water. To this, 2 wt.% Grassa 78 (Kievit, The Netherlands) was added (Grassa 78 is a powder containing 78 wt.% fat, 6% casemate and 16% lactose, obtained by spray-drying a caseinate-stabilized high-fat emulsion). The mixture was vortexed. After this, the fat drops from the cream powder were found to have been adsorbed on the surface of the drops of dextran solution.

The fat drops were then aggregated by adding 1 wt.% CaCh. Then the solution was diluted 5x with a 1 wt.% CaCk solution in demineralized water, the dextran and methylcellulose concentrations becoming so low that the dextran and the methylcellulose proceed to mix again, whereby the dextran drops dissolve in the continuous phase while the shells of bonded fat drops were left intact. When 5 wt.% EDTA (a calcium binder) was added and the pH was increased to around 7 or higher (so that the EDTA becomes active), the particle shells fell apart again.

Example 2

A suspension was prepared as described in Example 1. Instead of CaCb, 1 wt.% glucono-δ-lactate (GDL) was added to bring about aggregation so that the pH slowly decreased to 3-4 in a number of minutes.

If desired, 10 vol.% of a 0.5 wt.% alginate solution was added to further reinforce the shell, prior to diluting the solution 10x with a 1% GDL solution after waiting for 10 minutes.

Examples 3-10

Two-phase systems (water/water) were made by contacting a first solution of a first polymer (phase 1) in water with a second solution of a second polymer in water (phase 2), with, in each of the systems, colloidal particles concentrating at the interface between the two water phases.

¹ as in Example 1

² methylcellulose, as in Example 1

³ Vana Grassa 78 (Friesland Foods Kievit, the Netherlands), containing 78% emulsified fat with a volume-based average particle size of 0.39 μm (d50), 6% casemate, and 16% lactose.

⁴maltodextrin (6DE, Avebe, the Netherlands)

⁵Hiprotal 835 MP, Friesland Foods DOMO, particle size 1 μm (particles at interface and in phase 2)

⁶ reference particles of European Community Bureau of Reference with a volume-average particle size of 1.1 μm (d50) ⁷ emulsion prepared with ultraturrax 10% of Dimodan U/ J (unsaturated distilled monoglycerides from Danisco) in a 1% sodium caseinate solution at 60⁰C; drop size 0.2 μm (d50)

⁸ Lactobacillus paracasei CRL 431 (Chr. Hanssen, at least 3xlO¹⁰ CFU/g dried bacteria embedded in maltodextrin matrix)

Example 11

A 35 wt.% dextran solution in water and a 10 wt.% methylcellulose solution in water (in a ratio of 1:10) were prepared. A higher polymer concentration was used than in the previous examples to further delay the relaxation and/or the falling apart of elongated structures. To the methylcellulose solution, 2 wt.% fat particles were added (Vana Grassa 78). The dextran solution was then injected with a syringe (needle having an internal diameter of 1 mm) into the methylcellulose phase, while the needle was slowly drawn through the methylcellulose phase. Thus, elongated structures were obtained which were covered with particles.

Claims

1. A method of preparing a hollow body, comprising preparing a suspension comprising an aqueous discontinuous phase, an aqueous continuous phase and colloidal particles, and aggregating colloidal particles at an interface between continuous and discontinuous phase, thereby forming the hollow body.

2. A method according to claim 1, wherein the colloidal particles comprise particles chosen from the group of fat particles, monoglyceride and diglyceride particles, prokaryotic cells (such as probiotic bacteria), eukaryotic cells (such as endothelial cells) and protein particles (such as milk protein particles).

3. A method according to claim 1 or 2, wherein the discontinuous phase contains a polymer A and the continuous phase comprises a polymer B, different from polymer A, wherein polymer A and polymer B are chosen from the group of biopolymers, in particular from the group of proteins and polysaccharides, more in particular from the group of whey proteins (such as beta-lactoglobulins, alpha-lactalbumin, immunoglobulins), casein, dextran, caseinate, alginate, maltodextrin, starch, pectin, cellulose, including derivatives thereof.

4. A method according to any one of the preceding claims, wherein aggregation takes place with the aid of an electrolyte (such as calcium chloride) or an acid.

5. A method according to any one of the preceding claims, wherein aggregation takes place with the aid of coacervation.

6. A method according to any one of the preceding claims, comprising isolating the formed bodies.

7. A hollow body, preferably obtainable by means of a method according to any one of the preceding claims, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid, wherein the surrounding phase comprises at least one component chosen from the group of triglycerides, proteins, prokaryotic cells, eukaryotic cells, monoglycerides and diglycerides.

8. A hollow body, preferably obtainable by means of a method according to any one of claims 1-6, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, wherein the structure is at least substantially tubular.

9. A hollow body, preferably obtainable by means of a method according to any one of claims 1-6, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid, wherein the surrounding phase is at least substantially free of macropores, preferably at least substantially free of macropores and of mesopores.

10. A hollow body suitable for use in a foodstuff, preferably obtainable by means of a method according to any one of claims 1-6, comprising a surrounding phase which comprises aggregated and optionally merged colloidal particles, which surrounding phase at least substantially surrounds an aqueous liquid

11. A hollow body according to any one of claims 7-10, wherein the surrounding phase has an average thickness in the range of 0.1-10 μm.

12. A hollow body according to any one of claims 7-11, with a number-average diameter in the range of 1-100 μm.

13. A suspension, comprising hollow bodies prepared according to any one of claims 1-6 or hollow bodies according to any one of claims 7-12, suspended in aqueous continuous phase.

14. A foodstuff comprising hollow bodies preparable according to any one of claims 1-6, hollow bodies according to any one of claims 7-11 or a suspension according to claim 13.

15. A foodstuff according to claim 14, wherein the foodstuff is chosen from the group of dairy products, beverages, pastry and desserts.

16. A foodstuff according to claim 15, chosen from the group of cheese, yogurt, whipped cream, mousses, desserts, dairy beverages, ice-cream, δ cappuccino foam, toppings and cream bases.

17. Use of a hollow body according to any one of claims 7-11, wherein the surrounding phase comprises fat, as a fat substitute in a foodstuff.

18. Use of a hollow body according to claim 8 as a filter or as a liquid channel.