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Current Opinion in Colloid & Interface Science 15 (2010) 6172

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Current Opinion in Colloid & Interface Science

j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c o c i s

Delivery systems for liquid food products

Laurent Sagalowicz , Martin E. Leser
Nestl Research Center, Vers-Chez-Les-Blanc, CH-1000 Lausanne 26, Switzerland

a r t i c l e

i n f o

a b s t r a c t
One of the present challenges of the food industry is to deliver nutrition and health benets to the consumer while keeping, or improving the taste and aroma impact. Adding active ingredients to liquid food products for fortication is in most cases not possible or not sufcient to achieve the desired goal, due to the fact that many interesting micronutrients are only hardly soluble in aqueous systems and show (i) a limited stability against chemical or physical degradation, (ii) an incompatibility between the active ingredient and the food matrix, or (iii) reveal an uncontrolled release or bioavailability. Therefore, encapsulation systems, also denoted as delivery systems, are typically used to solve these formulation problems. The task to nd the appropriate delivery system is especially challenging for the food industry compared to other elds such as pharmacy, medical products or cosmetics, since only a limited amount of ingredients can be used as encapsulation and stabilization material. In the present review we will discuss the delivery systems available for (semi)-liquid foods and comment on existing advantages and limitations. The remaining technical challenges to solve in the future concern mainly the facts that (i) most of the available delivery systems for aqueous products do not yet allow to signicantly stabilize degradation sensitive encapsulated active ingredients against e.g. oxidation, (ii) the encapsulation (solubilization) capacity of some delivery systems is still quite poor and (iii) off-taste generation is possible above certain concentrations of added delivery systems. 2009 Published by Elsevier Ltd.

Article history: Received 2 December 2009 Accepted 7 December 2009 Available online 13 December 2009 Keywords: Delivery systems Emulsions Particles Surfactant self-assembly Nutrients Fortication

1. Introduction Consumers in the industrialised world are becoming increasingly aware of the relationship between diet and health. Thus, the demand for a balanced diet and functional food products that address specic health benets is growing steadily. Healthy food products, as compared to their standard counterparts, can be characterised by several attributes: containing (i) low to moderate sodium, sugar and trans-fat content, (ii) signicantly reduced energy density (iii) an increasing amount of whole grain and dietary bre, (iv) high quantity of milk and vegetable proteins, or (v) bioactive ingredients, i.e., nutrients which have health sustaining properties [1]. However, many of the nutritionally attractive micronutrients used for fortication cannot just be added to the product, since they are either only hardly soluble in aqueous systems, show a limited stability against chemical or physical degradation, or reveal an uncontrolled release or bioavailability. Moreover, the stability, bioavailability or bioefcacy of active substances strongly depend on the food matrix and the chosen (micro)encapsulation or delivery system [25]. Spray-drying (micro)encapsulation has been used in the food industry since the late 1950s to provide, especially for avour oils some protection against degradation/oxidation, and to convert liquids
Corresponding author. E-mail addresses: (L. Sagalowicz), (M.E. Leser). 1359-0294/$ see front matter 2009 Published by Elsevier Ltd. doi:10.1016/j.cocis.2009.12.003

to powders [6]. Microencapsulation is dened as a process in which tiny particles or droplets of the active ingredient(s) are surrounded by a coating, or embedded in a homogeneous or heterogeneous matrix, to give small capsules with many useful properties. Microencapsulation can also provide a physical barrier between different active ingredients in the solid product [7]. For example, iron can be isolated from vitamin A. One of the principal goals of microencapsulation nowadays is to protect the active ingredients from both chemical (e.g. oxidation) or physical (e.g. precipitation, crystallisation) degradation induced through exposure to oxygen, light, moisture, temperature or ionic strength changes or to allow controlled or sustained release of active ingredients under desired conditions, i.e., during eating or digestion. Due to the low diffusion coefcient of oxygen in the glassy capsule material and due to the relatively large particle size (usually larger than 200 m), sensitive oils, such as avours and essential oils can be stabilized up to several years [8]. Such an impressive delivery performance creates still today an enormous interest by food technologists in using microencapsulation based on spray drying, freeze drying, uid bed coating or extrusion [6,9]. In its simplest form, a solid microcapsule is a small sphere with a uniform wall around it. The material inside the microcapsule is referred to as the core, internal phase, or ll, whereas the wall is sometimes called shell, coating, wall material, or membrane [10]. The microcapsule may even have multiple walls. The choice of the wall material is very important for encapsulation efciency and microcapsule stability. The criteria for selecting a suitable wall material are mainly based on its physico-


L. Sagalowicz, M.E. Leser / Current Opinion in Colloid & Interface Science 15 (2010) 6172

chemical properties such as solubility, molecular weight, glass/ melting transition, crystallinity, diffusibility, lm forming and emulsifying properties or costs. Most used wall materials are biopolymers of various sources, such as natural gums (gum Arabic, alginates, carrageenans, etc.), proteins (milk or whey proteins, soy proteins, gelatin, etc.), starches, maltodextrins with different dextrose equivalents, corn syrup, waxes and their derivatives [10]. Fortication of liquid products, such as drinks, juices, etc, is getting more and more fashionable in foods. In this case the (micro) encapsulated active ingredients must be stabilized in a liquid environment, which is considerably different from stabilizing the active ingredients in a solid environment. Since almost all spraydrying processes in the food industry are carried out from aqueous feed formulations, the used wall material must be soluble in water at an acceptable level [6]. Solid microcapsules or powders cannot be simply added to an aqueous food product without losing the barrier and stabilization function of the solid capsule shell material. When adding the solid microcapsules into water, the capsule shell or matrix material is basically dissolved into the aqueous phase releasing the active ingredients into the liquid phase and, in general, protection against degradation is lost. Therefore, delivering active ingredients in a liquid matrix requires the use of different encapsulation and protection strategies. Obviously, the delivery of active ingredients in a uid aqueous phase is by far more challenging than the delivery of the active ingredients in a solid phase. Moreover, for liquids, appropriate encapsulation techniques depend critically also on the solubility characteristics of the active ingredients. For hydrophilic components, the suitable delivery strategies and capsules of choice differ very much from the approach to take for the delivery of lipophilic micronutrients. The list of micronutrients and bioactive substances, which are interesting to be added to food products is quite wide. Also their physico-chemical properties are very different. Most of them are extracted from plants, fungi, micro algae or marine biomass. Polyphenols, a class of dietary antioxidants, (primarily consisting of avonoids such as catechins, avones, isoavones, avonols, avonones and anthocyanins) capture free radicals, prevent lipids from oxidation and often exhibit antimicrobial and antiviral properties [11,12]. They, therefore, protect human cells and help reducing the risk of chronic diseases. Carotenoids, another class of important antioxidants, (e.g. lycopene, luteine, zeaxanthin, astaxanthin and carotene) also protect human cells from oxidative stress [13]. Essential poly-unsaturated fatty acids and their derivatives (e.g. docosahexaenoic acid, arachidonic acid) are another class of important nutrients, since they are required for the development of the human brain and play an important role in immunity [14]. Last but not least, various amino acids, peptides (e.g. glyco-macro peptides from milk) or proteins, vitamins, (CADEK), phytochemicals (e.g. phytosterols), minerals (calcium, magnesium, iron, zinc, selenium, chromium), and probiotic bacteria, are often added to food products to induce a range of different health-promoting and sustaining effects [15]. The successful development of bioactive containing delivery systems for liquid products depends on several factors: (i) the ability to disperse active ingredients into an aqueous phase, in case the actives are water insoluble, (ii) the stability of the capsule structure, preventing effects like creaming or sedimentation, (iii) minimising the impact on the textural, rheological or optical properties of the nal food product, (iv) protection of the encapsulated active molecules against degradation during processing and storage, and (v) controlled release during consumption, either in the mouth or during digestion in the GI tract. Most challenging in practical applications seems to be the sufcient stabilization of oxidation sensitive active molecules, such as vitamins or polyphenols. Moreover, masking possible off-taste effects or increasing (or controlling) the bioavailability or bioefcacy of the active ingredients during digestion are also quite demanding tasks to achieve in practical situations.

In this review, we will describe the different types of delivery systems which can be used for the fortication of liquid food products, and their interactions with the active molecules. We will mention the functionalities focussing on advantages and limitations of the available delivery systems. Finally, we will discuss some remaining challenges and speculate on what kind of research will be necessary in the future to develop further the science area of liquid delivery systems. 2. Systems available for the delivery in liquid food products In general, a wide selection of delivery systems is available for the use in food systems. Ultimately, one would like to relate the characteristics of the delivery systems to the functional attributes of the nal product, such as sensory, physico-chemical and biological/ nutritional impact [15,16]. Fig. 1 summarizes the various types of systems which can be used for the delivery of active ingredients in aqueous liquid products. Although solid microcapsules represent the large majorities of delivery systems used in food, since the available shell materials is very powerful in, for instance, protecting oxidation sensitive active ingredients from the contact with oxygen or heavy metals in powders, they are much less attractive for the delivery in aqueous systems, as mentioned above. Therefore, there is an increasing need to adapt the capsule material to liquid based products, i.e., the use of lipophilic materials, such as waxes or fats. An example are the solid-lipid (nano)particles. Other delivery strategies are exploiting the idea to build around ordinary emulsion oil droplets a multilayer structure, e.g. shell that is able to prevent contact of the encapsulated oily active ingredient with the aqueous continuous phase. The main activity in the research eld of aqueous delivery systems is, however, to try to physically or chemically complex or bind the active ingredient to a molecular or supramolecular structure with the hope to protect it in this way from chemical or physical deterioration. Examples of such delivery systems are cyclodextrin complexes, complexes with milk proteins, such as Na caseinate or whey proteins or their adequate aggregates, protein polysaccharide complexes, also denoted as coacervates, or complex formation with polysaccharides, like amylose. Self-assembly structure formation is also used for solubilizing (lipophilic) active ingredients into aqueous products. Prominent self-assembly delivery systems are micelles, microemulsions, liposomes or liquid crystalline particles, such as cubosomes, hexosomes and others. In this review, we will mainly focus on delivery systems that have a diameter less than about 12 m. Such colloidal systems are much less susceptible to creaming or sedimentation in the nal fortied liquid product. Therefore, we will exclude delivery concepts, which are only able to produce supra-micron particles. In order to avoid creaming/ sedimentation in the latter systems, the aqueous continuous phase has to be viscous or gellied or density matching components have to be added. 3. Oil-in-water emulsions Lipophilic active ingredients can be delivered in different forms. The best described and researched encapsulation system for lipidic materials in aqueous products are oil-in-water emulsions. Emulsions, such as, milk, yogurt drinks, dressings, sauces or mayonnaise, are ubiquitous in food. Their oil droplets can easily be used for the delivery of lipophilic active ingredients. For example, the delivery of the antioxidant vitamin E (tocopherol) is very important in food. Vitamin E is the major and most potent lipid-soluble antioxidant in vivo [17]. It functions as the major radical scavenging antioxidant in lipoproteins and efciently interrupts the chain propagation of lipid oxidation, thus protecting poly-unsaturated fatty acids and lowdensity lipoproteins from oxidation. Vitamin E or its derivatives are frequently added to the oil phase of o/w emulsion products for fortication reasons or in order to stabilize unsaturated oils against

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Fig. 1. Description of various kinds of delivery systems for liquid products. Advantages and limitations are briey summarized. The right column represents electron microscopy images of the various delivery systems. For the solid particles: SEM image of spray-dried particles, courtesy, J. Ubbink. For the emulsion: Cryo-TEM image of an oil droplet. For the complexes: freeze-fracture TEM image of a casein micelle. For the liposomes: Cryo-TEM of a unilamellar vesicle. For the microemulsions: Cryo-TEM image of a Tween 80 micellar solution. For the dispersed reversed surfactant systems: Cryo-TEM image of a particle having the internal structure of a reversed micellar cubic phase (space group Fd-3m).


L. Sagalowicz, M.E. Leser / Current Opinion in Colloid & Interface Science 15 (2010) 6172

Fig. 2. Schematic of a multilayered emulsion droplet stabilized by an emulsier (e.g. lecithin) and a polymer (e.g. chitosan). The large thickness of the interfacial layer as well as the positive net charge may be responsible for the measured increase in stability of the oil molecules against oxidation. Courtesy D. J. McClements.

oxidation [18,19]. Since vitamin E acetate is chemically more stable than vitamin E itself, it is especially used in food technology for fortication reasons. For many nutrients, however, a classical emulsion delivery system does not offer the desired properties in terms of solubilization (e.g. preventing crystallisation), protection against chemical degradation or inducing the desired nutritional activity. For example, classical emulsion systems do not protect unsaturated triglycerides, essential oils, vitamins A and D efciently against degradation. Therefore other ideas are needed to deliver such ingredients without losing their nutritional effect during shelf-life of the product. One way to achieve this is by controlling the composition and structure of the oil droplet interface, i.e., by building around the oil droplets multilayers of polymers or surfactants. 3.1. Multilayer emulsions McClements and co-workers showed that when stabilizing oil droplets rst with an anionic surfactant, such as a phospholipid, and then adding a positively charged polymer, such as chitosan to the emulsion, the droplets are coated with a surfactant-polymer membrane, which gives the globules a positive charge [2022] as depicted in Fig. 2. It was observed that this kind of emulsion protects more efciently 3 fatty acids and essential oils (citral and limonene) from oxidation that ordinary emulsions stabilized by a single surfactant or amphiphilic layer [2022]. The observed effect against oxidation of the oil droplets in this multilayer emulsion system was attributed to the net positively charged interface. A positive charge around oil droplets hinders the contact with transition metals, like iron or zinc, and as a consequence, prevents them to act as a pro-oxidant of the oil droplets. Note that lipid oxidation is known to be strongly catalyzed by transition metals, and preventing them to be in contact with sensitive oils can drastically increase the stability against oxidation. The relatively large thickness of the interface may also have a positive inuence in terms of a barrier function. In conclusion, an efcient control of the wateroil droplet interface reduces oxidation of sensitive oil droplets, like poly-unsaturated fatty acids (PUFA) [22], or essential oils such as citral and limonene [21] when compared to normally stabilized oil droplets. 3.2. Double emulsions Double emulsions, also often denoted as multiple emulsions, are emulsions of an emulsion, e.g. a water-in-oil emulsion dispersed in an aqueous phase (water-in-oil-in-water, W/O/W). Such emulsions are interesting as delivery systems, since, in principle, the water droplets inside the oil droplets can be used to deliver (unstable) hydrophilic active ingredients separating them from the outer aqueous phase of the

food product. Therefore, most studied applications of double emulsions are related to the control of the release of hydrophilic substances from the inner to the outer aqueous phase [23]. The main problems with food related applications of double emulsions are to nd the suitable foodgrade emulsiers and stabilizers for the inner and outer emulsion (to avoid mixing of the two type of emulsiers), and to prepare such emulsions in a form that they exhibit an acceptable shelf-life stability and desired controlled release behaviour. Recently, Benichou et al. [24] studied the double emulsion stabilization potential of WPI (Whey Protein Isolate)/polysaccharide (e.g. xanthan gum) complexes in comparison to each of the biopolymers alone. A synergistic positive effect with regard to the double emulsion stability was demonstrated, which was associated to modied surface properties induced by the adsorption of the complexes. The authors also showed that these double emulsions can be used for entrapping hydrophilic vitamins, such as vitamin B1, into the inner aqueous phase. By means of Differential Pulse Polarography it was possible to follow the real-time release of the entrapped vitamins from the core of the W/O/W double emulsion droplets to the outer aqueous phase. A similar study using biopolymerconjugates was published recently by Fechner et al. [25]. Another challenge is to entrap lactic acid bacteria into the inner water phase of double emulsions. Pimentel-Gonzlez et al. [26] reported on double emulsion encapsulated Lactobacillus rhamnosus cultured in sweet whey and harvested in the late log phase. The primary and double emulsion droplets showed practically no changes in their morphology and droplet size with aging time. The viability of the entrapped L. rhamnosus in the double emulsion was compared to that of nonentrapped control cells exposed to low pH and bile salt conditions. While the viability of the control cells decreased signicantly under low pH and bile salt conditions respectively, the survival of the entrapped cells increased signicantly under low pH and bile salt conditions. It was concluded that the double emulsion protected L. rhamnosus against simulated gastrointestinal tract conditions. This is a quite remarkable result. However, the successful use of double emulsions for the delivery of hydrophilic active ingredients is still critically depending on the progress we will make in the future in controlling the manufacture of such emulsions. Traditional fabrication by means of two subsequent emulsication steps leads to very illcontrolled structuring. Therefore, new approaches to control the quite complex structure of double emulsions are needed. For instance, Utada et al. [27] showed that by using a microcapillary (i.e., microuidics) device, it is possible to fabricate double emulsions that contained a single internal droplet in a very well dened geometry, e.g., a coreshell geometry. The authors showed that the droplet size can be quantitatively predicted from the ow proles of the uids, and encapsulation structures can be generated by manipulating the properties of the uid that makes up the shell. The high degree of control afforded by this method and the completely separate uid streams make this a exible and promising technique. Hanson et al. [28] showed, recently, that water-in-oil-in-water double emulsions can be prepared in a simple process (i.e., not in two steps, as usually is done) and stabilized over many months using single-component, synthetic amphiphilic diblock copolypeptide surfactants. The produced double emulsions were even stable against extreme ow, leading to direct mass production of robust double nanoemulsions that are amenable to nanostructured encapsulation applications in foods, cosmetics and drug delivery. Use of block copolypeptide surfactants overcomes key limitations of W/O/W double emulsions by allowing the straightforward preparation of stable nanoscale droplets that can simultaneously encapsulate both oil-soluble and water-soluble cargos. 3.3. Nanoemulsions Nanoemulsions, often also called miniemulsions, are emulsions consisting of droplets which are signicantly (by a factor of 10 or so)

L. Sagalowicz, M.E. Leser / Current Opinion in Colloid & Interface Science 15 (2010) 6172


smaller than the droplets present in ordinary emulsions [29]. As emulsions, they are thermodynamically unstable systems exhibiting, however, high kinetic stability which can be for several years [29]. Moreover their low viscosity and optical transparency make them very attractive delivery systems for example, in the pharmaceutical eld as drug delivery or other application area [30]. A direct consequence of the thermodynamic instability of nanoemulsions is that their formation requires external energy. There are two main preparation methods available [31,32]; the so called dispersion or high-energy methods, that consist of the application of high mechanical energy during emulsication, and the condensation or low-energy ones, in which a change of curvature and a phase transition takes place during the emulsication process. In condensation methods temperature (Emulsion Inversion Point method, EIP) or the composition (Phase Inversion Temperature method, PIT) is maintained constant. However, the preparation of nanoemulsions stabilized with ionic surfactants by condensation methods is not feasible, since the PIT method cannot be used, as temperature does not change the behaviour of ionic surfactants. The required change of curvature could be obtained in this case by varying the degree of ionization of the surfactant [31]. The very small droplet size of nanoemulsions (20200 nm) makes them resistant to physical destabilization via gravitational separation, occulation and/or coalescence [33]. Nanoemulsions are resistant to creaming because their Brownian motion is enough to overcome their low gravitational separation force. They are also resistant to occulation because of highly efcient steric stabilization. Most nanoemulsions are stabilized by synthetic surfactants which tend to have long hydrophilic tails of the order of 210 nm. The high ratio of steric layer thickness to droplet diameter (/r ratio) means that steric stabilization is very effective and even weak occulation is prevented. However, nanoemulsions are particularly prone to a growth in particle size over time by a process known as Ostwald ripening [33]. Ostwald ripening is a process whereby the larger droplets in an emulsion grow at the expense of the smaller droplets because of molecular diffusion of oil between droplets through the continuous phase. This process is driven by the Kelvin effect where the small emulsion droplets have higher local oil solubility than the larger droplets because of the difference in Laplace pressure. The rate of Ostwald ripening is largely dictated by the solubility of the oil in the continuous phase C() [33].The aqueous phase solubility of an oil decreases linearly with oil molar volume, Vm. Therefore, low molar volume oils (200350 cm3 mol 1) show an appreciable solubility in water resulting in destabilization by Ostwald ripening. On the other hand, the large molar volume of long chain triglyceride oils ( 900 cm3 mol 1) should make them insoluble in water thus preventing Ostwald ripening. Note that the formation of true triglyceride oil nanoemulsions appears, however, difcult mainly because of the relative high viscosity of the triglyceride oil. In order to slow down Ostwald ripening in oil-in-water nanoemulsions, in which the oil is relatively soluble in the water phase, such as essential oils, a second oil with much lower continuous phase solubility, such as high molecular weight triglyceride oils, can be added to the smaller molecule oil phase [33]. This concept is already known for years and is based on the premise that the entropy of mixing provides a chemical potential that opposes Ostwald ripening. When a mixed oil nanoemulsion undergoes Ostwald ripening, the soluble oil has greater mobility between droplets. Over time, larger droplets become enriched with the soluble oil and smaller droplets become enriched with the insoluble oil. This creates a compositional imbalance that is of higher entropy than a perfectly mixed system. An advantage of using nanoemulsion instead of ordinary emulsion delivery systems lies in the fact that the bioavailability and bioefcacy of the delivered lipophilic bioactives can be expected to be greater when delivered in form of a nanoemulsion instead of a normal emulsion. Recently, Wang et al. [34] described the anti-inammation activity of curcumin when delivered through o/w nanoemulsions

stabilized by Tween 20. The authors could show that 80 nm nanoemulsion droplets exhibit higher anti-inammation activity than emulsions containing 620 nm sized emulsion droplets. Interestingly enough, when delivering the curcumin in a micellar Tween 20 solution the biological activity (inhibition on the edema of mouse ear) is signicantly lower than when delivering the active ingredient in form of an emulsion or nanoemulsion. Although the measured effects are quite striking, the exact structurefunction relation in this system is by far not claried. Recently, Wulff-Prez et al. [35] studied nanoemulsions from natural oils like soybean, olive and sesame oil that can be used to deliver lipophilic bioactives in parenteral nanoemulsions produced by means of ultrasound homogenisation. As emulsier the non-toxic triblock ABA-type copolymer surfactant Pluronic F68 was used. At relatively low surfactant concentrations the emulsions proved to be stable against Ostwald ripening and coalescence, even in the presence of relatively high oil droplet volume fractions (0.25). At higher polymer concentrations, however, a reversible occulation destabilization (depletion occulation) was observed showing the subtle effect of other structures, present in the product, on the physical properties of the nanodroplets. Yuang et al. [36] investigated oil-in-water nanoemulsions of -carotene produced by high pressure homogenization. While the physical stability of the nanoemulsions, which were stabilized by polysorbate emulsiers, was quite acceptable, signicant chemical degradation of the delivered -carotene occurred during storage. This study clearly shows that although nanoemulsions can be formulated also for food applications in a (relatively) stable form, the main remaining challenge is to achieve also an acceptable bioactive stability against chemical degradation during processing and storage of the fortied product.

4. Solid lipid nanoparticles Solid lipid nanoparticles carriers (SLNs) have some similarities with nanoemulsion systems. The diameter of such lipid particles can be also quite small, i.e. in the range between 50 nm and 1 m. The main difference is, however, that the SLNs consist of a solid or semi-solid lipidic core containing lipophilic active ingredients. Active ingredients can be solubilized homogeneously either in the core of the SLNs or in the outside part [37]. The advantage of SLNs as delivery system for lipophilic active components is reported to lie in the immobilisation of active elements by the solid particle structure leading to an increased chemical protection, less leakage and sustained release [38,39]. This physical property allows a better control of both the physical (against recrystallisation) and chemical (against degradation) stability of the delivered nutrients. The preparation of SLNs is achieved by heating the lipidic core components above their melting point, and then using common emulsion or microemulsion technology, i.e., homogenisation or mixing of the melted lipidic phase with a cold aqueous solution generating re-crystallised lipidic particles. The main difculty associated with SLNs production is to control the lipid polymorphism. Triglycerides, for example, can be present in three different crystalline structures , , and . Bunjes et al. [40] showed the different crystal structures and morphologies these particles can have using a combination of X-ray diffraction, Cryo-transmission electron microscopy (plunging technique) and freeze-fracture electron microscopy. While the structure gives a shape close to a sphere, the structure adopts a needle or platelike shape with much less defects. This suggests that only the form is suitable as delivery system since the structure is relatively defective while the crystals of the and structures are much more perfect in their crystal structure ejecting the encapsulated active elements to the outside of the particle. In addition, the plate-like crystals of the form have a tendency to grow much more leading to destabilization and to gel formation. Therefore, it is of prime importance to control particle crystalline structure, i.e., preferably being in the lattice.


L. Sagalowicz, M.E. Leser / Current Opinion in Colloid & Interface Science 15 (2010) 6172

Formation of a certain crystal structure depends on many factors, such as lipid composition, cooling rate and present crystal habit modiers, as surfactants. High cooling rates favours the presence of the less stable form, while low cooling rates favours the presence of more stable crystals [38]. Surfactants may stabilize a given crystal form. It was recently found that a blend of saturated long chain phospholipids and bile salts stabilize the form [41]. Concerning the effect on the encapsulated active ingredients, there is evidence that SLN particles can protect sensitive bioactives from degradation such as hydrolysis or oxidation [39]. Vitamin A is sensitive to degradation by oxidation and polymerisation, which are catalyzed by light and transition metals [2]. Carlotti et al. [42] found that between 50 and 70% of retinol remains undegraded when encapsulated in SLNs made of Cetyl palmitate (30% of vitamin A was degraded), Glyceryl behenate (49% degradation) and palmitic acid (34% degradation), while 8% retinol remains when delivered in standard oil-in-water emulsions. An important application of SLNs is in the eld of controlled drug release [39]. Yang et al. [43] showed that camptothecin, which is an anti-tumor agent can be released for up to one week when solubilized into SLNs. It is supposed that when nutrients are solubilized in the inner core of SLNs, there will be sustained release, while solubilization in the outside shell or in the solid solution will give rise to a burst release [39]. SLNs can also control the penetration of several actives into the skin, which makes them attractive for cosmetic applications and topical delivery [44]. In conclusion, SLNs seem to have a large potential for the protection of active components, but the lack of physical stability (e.g. transformation of the crystal into or resulting in particle growth and ejection of loaded active molecules), is at present the major issue when trying to apply them as a delivery system for food. In addition, active elements may be exposed to high temperatures during the preparation of the lipid carrier material leading to chemical degradation. Finally, saturated lipids are needed to obtain these kinds of delivery system. Such lipids are not the preferred ones in terms of nutrition and health. 5. Molecular complexes Another strategy to deliver active ingredients in aqueous foods is by physically complexing them with other molecules, hoping that in this way a better solubilization and/or an increase in the chemical stability of the complexed bioactive can be achieved. In this context a molecular complex is referring to the physical association between a host and a guest (active ingredient) molecule. The most studied host molecules are the cyclodextrins. However, molecular association with other polysaccharides (e.g. amylose) or proteins or their aggregates can also be achieved. 5.1. Cyclodextrins Cyclodextrins (also abbreviated as CD) are cyclic (or taurus shape) oligosaccharides having a hydrophilic outer surface insuring good dissolution of the complex in an aqueous environment (Fig. 3a). Cyclodextrins contain a lipophilic cavity enabling to host relatively small lipophilic or amphiphilic constituents (Fig. 3b), such as fatty acids, vegetable and essential oils, nucleic acids, vitamins and hormones [45,46]. There are three main types of cyclodextrins: (i) , corresponding to 6 glucopyranose units linked by -(1,4) bonds, (ii) , corresponding to 7 units (U) and (iii) , corresponding to 8 U. The dimensions of the internal cavity are crucial for the encapsulation of guest molecules. Only molecules, which t physically into the cavity can be incorporated. The cavity diameter varies between 0.5 and 0.8 nm which is relatively small allowing the solubilization of only relatively small molecules. Long guest molecules may not be protected in an optimal way due to the limited height of the taurus [46]. Since 2008, -cyclodextrin is recognised as a novel food ingredient. While the -form is authorized in all countries, the -form can only be

used in certain countries; it is, for instance not authorized in Europe (yet). The large majority of published applications of cyclodextrins are in the eld of pharmaceutics. Interest comes from the fact that cyclodextrins considerably help molecular solubilization and thus can increase biodisponibility, bioavailability and bioefcacy [47]. In addition, drugs can be protected against photodegradation and hydrolysis when solubilized into cyclodextrin [47]. Concerning food applications, CD can be used for avour protection or avour delivery and to reduce bitterness and bad smell and taste [48]. In food, the most used application concerns the removal of cholesterol in animal products such as eggs [48,49]. Lin et al. [50] and Mumoz-Botella et al. [51] showed that cyclodextrins protect retinoids (vitamin A) from photodegradation. After 60 min of exposure to light, 44.3% of all-trans retinoic acid remains when solubilized in cyclodextrin while 31.8% remains intact when present in ethanol. The main limitation of using cyclodextrins is related to their moderate and limited loading capacity since there is always an equilibrium between the amount of molecule solubilized in the cyclodextrin cavity and outside [46]. Loading of eugenol, inside -CD, was found to be 90% while it was 100% when using an emulsion diffusion method with polycaprolactone [52]. The loading capacity of a delivery vehicle, i.e., the molar ratio between the encapsulated and encapsulating material is a very important property characterising the encapsulation efciency of a delivery system. Choi et al. [53] observed by means of transmission electron microscopy aggregation between sh oil and -CD. In the presence of 10 times more -CD than sh oil, hexagonal-type aggregates having a diameter of 300 nm, are observed. It seems that the cyclodextrin is at the outside of these aggregates, and most of the sh oil is in the inside of the CD particle structure. In the presence of a ratio of 1:1 between sh oil and -CD, other types of supramolecular aggregates are formed. Their diameter is in the range of 600 nm. This study indicates that CDs cannot only complex molecules in their cavity in a molecular form, but that cyclodextrin molecules can also form a sort of self-assembly structure, which is able to encapsulate especially large molecules like triglycerides. In addition, the process to solubilize guest molecules in cyclodextrins is relatively complex and full equilibrium solubilization is obtained only after one week [48].

Fig. 3. Schematic representation of the structure of the cyclodextrin ( form in the drawing) molecule and the mechanism of drug (nutrient or aroma) complexation. (a) Cyclodextrin structure view from different angles. (b) Complexation with a drug molecule. Adapted from Davis and Brewster [46].

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5.2. Molecular association with biopolymers Active molecules can form physical complexes also with a variety of other naturally occurring food components. Such systems are the base for designing natural delivery systems. An example is amylose present in starch, which can adopt a helical structure generating a cavity of about 0.5 nm in diameter. Small molecules like aromas can be solubilized in this cavity. It is known already for a little while that starch granules, which contain amylose, can strongly inuence aroma release [54]. Amylose complexes can from either an amorphous or crystalline structure. Slight hydroxypropylation of starch provides a route for obtaining soluble complexes which do not aggregate [54]. Although amylose has some similarities to cyclodextrins, it is much less used and studied as a delivery system for aqueous systems. Proteins and peptides are amphiphilic molecules. They are also relatively soluble in water and can bind lipophilic or amphiphilic active ingredients. Semo et al. [55] used casein micelles to solubilize vitamin D2. Sodium caseinate, CaCl2 and K2HPO4 were used to encapsulate the vitamin and reconstitute the casein micelle solution. It was found that the casein micelle can provide a partial protection against UV-lightinduced degradation compared to the serum media (of the casein micelle dispersion), which was used as a control [55]. Zimet et al. [56] used -lactoglobulin and -lactoglobulin complexed with pectin as delivery system for 3 PUFA. Optimum -lactoglobulin complexes had a diameter of about 100 nm and were claimed to protect PUFA during a stress test at 40 C at pH = 7. More precisely, it was found that the various samples tested could be ranked in order of increasing protective effects as follows: DHA in water < DHA in -lactoglobulin < DHA in -lactoglobulinpectin complex. A more detailed review on the use of milk proteins as vehicles for bioactives is published by Y. Livney in the same section of this journal [57]. 6. Self-assembly delivery systems Self-assembly structures, such as micelles, microemulsions, and liquid crystalline phases, are formed by the spontaneous association of surfactants in aqueous (or oil) phases. Surfactants are used in many food applications, such as in bread and cake production for the improvement of shelf-life (prevention of starch retrogradation due to formation of monoglycerideamylose complexes) and avour retention [58]. Another important application of surfactants deals with the control of emulsion or foam formation and stabilization. All these applications are based on the potential of amphiphiles to adsorb at interfaces or to crystallise and co-crystallise with other molecules. An intriguing characteristic of amphiphiles is their capacity to form various self-assembly structures when added into water. For food, this property is mainly seen with polar lipids, such as monoglycerides and phospholipids [5962]. Amphiphiles are molecules containing a lipophilic part and an amphiphilic part. If mixed with water, the lipophilic hydrocarbon part of the molecule will be shielded from the water molecules by the formation of self-assembly structures. Therefore, the self-assembly process is spontaneous, meaning that no energy (homogenisation) is required to form the structure. However, in reality the situation is not so simple since many surfactants in food are at least partly crystalline at room temperature forming some sort of crystals. Thus, only at temperatures, higher than their melting temperature (Krafft temperature) self-assembly structure formation is induced. One of the most useful (and simple) concept, for a semiquantitative description of the relation between surfactant molecular shape and self-assembly phase formation, was given by Israelachvili et al. [63] and Tanford [64] who dened the so-called dimensionless surfactant packing parameter P. P = V = al

where V is the molecular volume of the hydrophobic moiety, l the molecular length of the hydrocarbon chain and a is the effective (or hydrated) cross-sectional area of the polar head-group. Depending on P, different self-assembly structures can be formed (see Fig. 4). If P is small (P 1), structures like normal micelles, hexagonal (Hi) or cubic phases are formed. If P is close to 1, a lamellar liquid crystalline (L) phase is formed, which when dispersed into water gives rise to vesicles or liposomes formation. If P is large (P 1), reversed selfassembly structures, such as reversed micelles, reversed hexagonal (Hii) or reversed cubic structures are formed. In the following we describe the use of self-assembly structures in the delivery of active ingredients in aqueous media, focussing on (i) micelles (or microemulsions), (ii) liposomes and (iii) dispersed reversed self-assembly structures. The advantage of using surfactant self-assembly structures is that the compartmentalisation degree of the structures is very high, i.e., the characteristic solubilization domains are very small (in the order of 10 nm). As a consequence, the created interface between the aqueous and lipidic domain is extremely large. Ericson et al. [65] reported that, for instance, the reversed gyroid bicontinuous cubic phase forms a surface area of 400 m2 g 1 phase. The presence of this tremendous amount of interface allows to create new delivery functionalities, which are basically linked to the possibility to preferentially solubilize amphiphilic active ingredients into such structures. This offers new opportunities to control chemical reactions such as oxidation or Maillard reaction in such systems [6668]. 6.1. Micelles and microemulsions Oil-in-water microemulsions (also called lled micelles; lled with lipophilic guest molecules), unlike o/w nanoemulsions, are thermodynamically stable and are formed spontaneously. Although both systems show long-term stability (due to a different mechanism, however) microemulsions are much more sensitive to environmental changes, such as temperature, ionic strength, composition (adding/ removing molecules to/from the aqueous continuous phase). A drawback when comparing to nanoemulsions, is that microemulsion formation requires the use of relatively large amounts of surfactant, i.e., their loading capacity is signicantly lower than this of comparable nanoemulsion delivery systems, especially when using triglycerides as the dispersed oil phase. Moreover, making food-grade microemulsions is still quite challenging because of the limited choice of suitable foodgrade emulsiers. The best investigated class of food surfactants for microemulsion formation is the polysorbates (Tweens) [59]. In spite of the above mentioned limits, the use of o/w microemulsions for the delivery of active ingredients is a widely investigated research eld [6971] both for pharmaceutical and food applications. In this chapter we will concentrate mainly on new developments in this eld. In the past, the research group of N. Garti showed in various publications the excellent solubilization effect of microemulsion systems for lipophilic nutrients, such as -carotene, lycopene, lutein or phytosterol [70,71]. However, the question concerning the nutrient chemical stability in such microemulsion delivery systems over time was investigated in a much lesser extent, and we do not know yet whether o/w microemulsion systems principally stabilize or destabilize solubilized lipophilic molecules against degradation. This is, as an example, the case for the chemical stability of lycopene or -carotene in o/w microemulsions as mentioned by Loveday and Singh [2]. Garti et al. [72] reported that on exposure to sunlight, lycopene degrades more slowly in o/w microemulsions than in an organic solvent. However, Szymula [73] showed that -carotene degradation in sunlight was fastest in o/w microemulsions, followed by water-in-oil (w/o) microemulsions and pure pentanol. The authors suggest that the high concentration of -carotene in the oil droplets of the o/w microemulsion promotes degradation. A certain delivery system may have some


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Fig. 4. Summarizes the different existing surfactant self-assembly structures as function of their Packing parameter P. Going from top to bottom, corresponds to an increase in the Packing parameter; inspired by Jnsson, et al. [96]. (b) Cryo-TEM image of a particle having an internal reversed hexagonal phase. Reprinted with permission from Yaghmur et al. [85]. Copyright (2005) American Chemical Society; (c) Cryo-TEM from a particle having an internal reversed bicontinuous cubic phase structure (primitive surface, space group Im3m), adapted from Sagalowicz et al. [97], (d) Cryo-TEM of a vesicle, which is obtained by dispersing a lamellar liquid crystalline phase into water; (e) Cryo-TEM of a micellar phase obtained from a Tween 80 solution; images and gure adapted partially from Sagalowicz et al. [61].

benets for a given bioactive under certain conditions added to a certain matrix, but may have a negative effect applied under (slightly) other conditions. Recently, Feng et al. [74] studied vitamin E (present in its stable acetate form) containing microemulsions based on nonionic emulsiers. Focus was put on determining the release rate of vitamin E from the microemulsion using a dialysis bag-Ultraviolet Spectrophotometer combination, and the evaluation of vitamin E cytotoxicity when laden microemulsions were exposed to human cancer cells. The results show that the vitamin E microemulsion system induces a slight sustaining release effect when compared to the vitamin E release from the ethanol reference system. Moreover, cell toxicity of the microemulsion was lower than that of the single components. Sim et al. [75] investigated the oxidation of methyl linoleate, an amphiphilic unsaturated oxidation sensitive model bioactive, when solubilized in Tween based o/w microemulsions in the presence of a chlorogenic acid and tocopherol antioxidant mixture. Understanding the synergistic effects between these two types of ingredients is of great interest when trying to develop new strategies for increasing the stability of oxidation sensitive nutrients. The presented results demonstrate that chlorogenic acid and vitamin E exhibit a strong synergetic effect. This may have implications for the nutritional values of products, which contain chlorogenic acid and its analogues, such as coffee. However, we still need a better insight in the mechanism of the synergistic action in order to use these results for the development of other potent antioxidant mixtures. Moreover, more systematic data are needed to better understand the differences observed in the antioxidant activity as a function of structure formation (e.g. bulk vs emulsions vs microemul-

sions). Zhang et al. [76] published, recently, a study on antimicrobial performance against Bacillus subtilis (a foodborne bacterial pathogen) of a microemulsion system which consisted of glycerol monolaurate GML) as the oil, Tween 20 as the surfactant, ethanol as the cosurfactant, sodium lactate (SL) and water. The obtained results showed that the used microemulsion formulations were effective in inhibiting the viable bacteria cells and the bacteria growth, and that the solubilization of SL into the microemulsion created a synergistic antimicrobial activity. This work indicates that microemulsions are promising delivery vectors also for antimicrobial applications for the food industry. However, also in this case we need more insight in the molecular mechanism and the contribution of the interface present in microemulsion systems. 6.2. Liposomes Liposomes, often also denoted as vesicles, are formed when the surfactant molecules have a Packing parameter P close to 1. Contrary to microemulsions their formation is often not completely spontaneous. When mixed with water the surfactant spontaneously forms a lamellar phase, which then needs to be dispersed to form vesicles. Liposomes can contain (i) one bilayer forming unilamellar vesicles (ULV), (ii) several concentric bilayers forming multi lamellar vesicles or (iii) non concentric bilayers forming multi vesicular vesicles (MVV). The size of these structures can be rather small (in the range of 20 nm) or rather large (exceeding 1 m). The most common procedure to form vesicles consists of evaporating a surfactant, such as phospholipid or cholesterol, chloroform/methanol solution to form a phospholipid-

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based lm [77]. The subsequent addition of an aqueous phase and shear is necessary to obtain the vesicle dispersion. Due to the use of toxic solvents, this method is not adapted to food. However, other methods are also available, such as using a microuidizer, or membrane extrusion. So far, a lot of delivery applications have been developed for the pharmaceutical industry. In principle, liposomes can encapsulate hydrophilic molecules in their inner aqueous compartment while amphiphilic and/or lipophilic ingredients can be delivered inside the bilayer structure. A great variety of natural and synthetic molecules can be used allowing also targeted delivery [77]. Attachment of PEG moieties, for example, on the vesicle surface, prevents them from being destroyed by monocites and macrophages in the liver and spleen ensuring prolonged circulation in the blood stream. The use of vesicles or liposomes in food applications is still today quite limited. This is most probable due to (i) the relatively high costs of pure lecithins, the best surfactant for making food liposomes, (ii) the relatively low encapsulation efciency and (iii) the relative complicated fabrication equipment. Most prominent application in food industry is for the encapsulation of cheese ripening enzymes in order to improve the enzymatic function and enabling a homogeneous repartition of the enzyme within the cheese product [78,79]. In a recent study, Folmer et al. [4] investigated the uptake of tocopherol using a Caco-2 cell model. The main idea was to nd out whether differences in structure formation and/or hydrophilicity of the used tocopherol derivative would induce a different tocopherol uptake behaviour. Two tocopherol succinate derivatives, where two different hydrophilic ethyleneglycol chains were attached to the tocopherol succinate, were used. Those are the tocopherol hexaethylene glycol succinate (denoted as D1), which forms vesicles in water, and the tocopherol dodecaethylene glycol succinate (denoted as D2), which forms elongated micelles in water (Fig. 5). D1 or D2 were either solubilized into mixed micelles using bile (taurocholate) acids, monooleins, lysophosphatidylcholine and oleic acid or used as such in water. When, the derivatives were solubilized into mixed micelles, D1 showed a slightly but signicantly more efcient esterase transformation into tocopherol and tocopherol succinate and subsequent uptake of these constituants into the cells than D2. This must be related to the different efciency of the hydrolytic reaction of the esterase. The situation was completely changed when D1 and D2 were just mixed into water (and not incorporated into mixed micelles). In this case, the total hydrolysis and uptake into the cells was about two folds lower for D1 than for D2. Obviously, elongated micelle structures are much more efcient than vesicles in terms of tocopherol bioavailability. This result demonstrates that the type of the formed self-assembly structure can also play a crucial role in determining the bioactivity of active ingredients such as tocopherol. 6.3. Dispersed reversed self-assembly structures Reversed phases are made out of surfactants that have a Packing parameter P >1 (see Fig. 4). They are formed by lipophilic surfactants such as unsaturated monoglycerides or phospholipids. One of the most studied reversed system is the reversed bicontinuous cubic phase. Possible applications, such as for molecular protection, controlled release, prevention of molecular aggregation or changes in chemical reaction were demonstrated in the past and seem to be particularly attractive to the pharmaceutical or cosmetic industry [80]. One of the main features of the cubic phase is its high viscosity which makes it difcult to handle and to use. However, Larsson and co-workers found efcient means to disperse these reverse structures into water making them also available as delivery systems for aqueous liquids [8183]. Two limitations still remain. Firstly, taste issues may appear if a certain threshold concentration in the nal aqueous product is exceeded, and secondly, it was demonstrated that when a dispersion of a bicontinuous cubic phase (a so-called cubosome dispersion) is mixed with an emulsion, a new type

Fig. 5. Top: Cryo-TEM image of vesicles formed when D1 is mixed with water. Bottom: Cryo-Tem image of the rod-like micelles formed when D2 is mixed with water.

of dispersion is formed, in which the inner structure of the dispersed particles was not anymore bicontinuous cubic [84]. More recently also other reversed phases and their dispersions were studied in more depth. Examples are the reversed hexagonal phase (Hii), the reversed micellar cubic phase (space group Fd-3m) the reversed microemulsion and the sponge (L3) phase [8589]. Interestingly enough, the functionality of these phases was very different and clearly depended on their nanostructure: for instance, the reversed hexagonal phase showed a more sustained release than the cubic phase, and the glucose diffusion coefcient was about 10 times lower in the reversed hexagonal phase than in the bicontinuous cubic phase [90,91]. Release of entrapped/solubilized molecules can also be tuned by switching from one phase to another one by, for instance, changing temperature inducing a transition from, e.g. cubic to hexagonal [91]. Reversed hexagonal and micellar cubic phases contain, like the cubic phase, a large amounts of surfactant and therefore have some limitations for use in food products, essentially when a relatively large amounts of delivery system has to be added in order to create the desired nal benet in the product or during consumption. In this respect, reversed microemulsion dispersions can be obtained with much less surfactants. These structures are quite attractive, since new functionalities, which are associated with the unique internal microemulsion structure of the oil droplets, could be created. For example, it was shown that reverse microemulsion droplets can solubilize non-esteried phytosterol molecules in much larger amounts than in ordinary oil droplets can do. Michel et al. [92] reported that 15% phytosterol could be solubilized in molecular form into reversed microemulsion droplets dispersed in milk without inducing signicant re-crystallisation of the phytosterol over time while the same amount of phytosterol could not be solubilized in normal oil droplets without recrystallizing (Fig. 6). Another interesting application of reversed microemulsion droplets deals with the controlled release of aromas. In particular, when reducing oils and fats in food products, aroma release gets unbalanced and amphiphilic and lipophilic aroma molecules are subjected to a so-called burst release.


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Fig. 6. Polarized light microscopy of milk where (left) the oil was loaded with non-esteried phytosterols prior to homogenization, and (right) a reversed microemulsion phase was loaded with non-esteried phytosterols prior to homogenization. In polarized microscopy, non crystallised oil droplets are not visible. Images were taken after several weeks of storage at 4 C. Notice that for the O/W emulsion (left), there are many phytosterol crystals visible while for the dispersed reversed microemulsion (right), there is no phytosterol crystal.

In the past it was shown that a bulk reversed bicontinuous cubic phase containing 20 or 30% water generates a unique release prole of aromas when compared to the prole obtained with other structures, such as oils or w/o emulsions [93]. More recently, Landy et al. [94] investigated the release of individual aroma molecules in more details by means of gas chromatography mass spectrometry (GCMS). The release from a water-in-oil microemulsion (10% water60% unsaturated monoglyceride) was compared to the release from a water-inoil emulsion (10% water5% polyglycerol polyricinoleate (PGPR)85% sunower oil) and from pure sunower oil. For almost all used lipophilic aromas the release from the microemulsion was less than from the oil and from the emulsion. The results were especially impressive for octanol and butanol, two aroma molecules with amphiphilic character (Fig. 7). Phan et al. [95] looked at the static and dynamic release behaviour of a dispersed water-in-oil microemulsion (composition: 0.25% unsaturated monoglyceride4.75% medium chain triglyceride (MCT)0.8% sodium caseinate94.2% water) compared to a normal oil-in-water emulsion (5% medium

chain triglyceride (MCT)0.8% sodium caseinate94.2% water). It was found that the aroma release from the dispersed microemulsion was lower and the release dynamics delayed when compared to the release from the corresponding emulsion. Clearly, the presence of a high interfacial area within the microemulsion system signicantly inuences (and slows down) the release behaviour of aroma molecules when compared to the corresponding oil or emulsion system. 7. Conclusion and outlook In this work we presented and described various types of delivery systems which are used for the fortication of liquid food products. They all have advantages and limitations as depicted and summarized in Fig. 1. Most delivery systems are able to solubilize lipophilic nutrients into aqueous products. Concerning the appearance of the nal food product, only nanoemulsions, microemulsions and some complexes are able to keep the product transparent, if desired

Fig. 7. Release of aroma molecules into the headspace using a water-in-oil microemulsion (L2) and a water-in-oil emulsion (w/o) as a function of logP of the used aroma molecules. LogP is representing the octanol-water partitioning coefcient of the different aroma molecules. Low LogP means good solubilization into water; while high LogP means large solubilization into octanol. The release data were normalized by the corresponding release from pure medium chain triglyceride (MCT) oil. It can be noticed that the release from both the microemulsion and emulsion is less than the one from the pure oil. More important to see is that, for butanol and octanol, which are two quite surface active aroma molecules, the release from the microemulsions is about half of the release measured from the emulsion system. These effects can be attributed to the large interface present in the microemulsion, which is able to solubilize surface active molecules and thereby signicantly changing the release behaviour of interfacially active aromas into the headspace. Adapted from Landy et al. [94].

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especially for some beverage formulations. Most of the described systems suffer either (i) from some regulatory issues concerning the used carrier material, or (ii) from an insufcient loading capacity restricting their use for the delivery of nutrients in only small concentrations. Most challenging, however, is to achieve also an appropriate chemical stability of the delivered active ingredients during the shelf-life of the liquid product. Realizing a sufcient chemical stability of the delivered nutrients and aromas in the fortied end product is probably the most desired functionality that the delivery system must accomplish. We think that most probably signicant technical advances in this eld will come when we will better understand how chemically unstable nutrients, like the PUFAs or vitamins, are stored and protected in their natural environment. We also believe that still much progress can be done when we will get a better understanding of the origin and the full mechanism of the chemical degradation in each fortied product. In contrast to the delivery in powdered products, it seems that for the delivery of active ingredients in liquid products, there is no generic solution available which can solve most of the delivery problems we are facing. Every solution is very unique and depends very much (i) on the nal product matrix and packaging, (ii) on the active ingredient(s) to be delivered and (iii) on the chosen delivery system and its physico-chemical properties. References
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