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Food
This paper was published in Soft Matter as part of the
Food Science web theme issue

This Soft Matter theme issue explores fundamental interdisciplinary research into food science covering a
variety of themes including food biophysics, food colloids and emulsions, and complex food structure. Please
take a look at the full table of contents for this issue.
Published on 06 August 2008 on http://pubs.rsc.org | doi:10.1039/B804863K
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Guest Editor:
Professor Peter Fryer,
University of Birmingham
Papers include:
Aggregation in β-lactoglobulin
Athene M. Donald, Soft Matter, 2008, 4, 1147
DOI: 10.1039/b800106e
Microstructure of fat bloom development in plain

and filled chocolate confections
Dérick Rousseau and Paul Smith, Soft Matter, 2008, 4,
1706
DOI: 10.1039/b718066g
Food structure and functionality: a soft matter perspective

Job Ubbink, Adam Burbidge and Raffaele Mezzenga, Soft Matter, 2008, 4, 1569
DOI: 10.1039/b802183j
Interfacial structure and stability of food emulsions as affected by protein–polysaccharide interactions

Eric Dickinson, Soft Matter, 2008, 4, 932
DOI: 10.1039/b718319d
The influence of electrostatic interaction on the structure and the shear modulus of heat-set globular protein gels
Soraya Mehalebi, Taco Nicolai and Dominique Durand, Soft Matter, 2008, 4, 893
DOI: 10.1039/b718640a
Direct observation of adhesion and spreading of emulsion droplets at solid surfaces

Diane M. Dresselhuis, George A. van Aken, Els H. A. de Hoog and Martien A. Cohen Stuart, Soft Matter, 2008, 4, 1079
DOI: 10.1039/b718891a
You can read the rest of the articles in this issue at www.rsc.org/softmatter/food
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REVIEW www.rsc.org/softmatter | Soft Matter
Colloidal delivery systems for micronutrients and nutraceuticals†

Krassimir P. Velikov* and Eddie Pelan*
Received 20th March 2008, Accepted 18th June 2008
First published as an Advance Article on the web 6th August 2008
DOI: 10.1039/b804863k
The formulation of micronutrients and nutraceuticals in the design of functional foods brings
enormous technological challenges. The incorporation of micronutrients and/or nutraceuticals can
compromise the product functionality. Issues often encountered are related to unwanted changes in the
product physico-chemical stability, appearance, texture, flavour, taste and bioavailability due to
inherited instability or interactions with other ingredients. This review intends to present the general
strategies in using colloidal dispersions as delivery systems for micronutrients and nutraceuticals.
Some illustrative examples will be given on how colloidal delivery systems can be utilised in the design
of novel functional foods.
Introduction important properties is that we have a means to control their

composition, morphology, surface properties, and interactions
Colloidal dispersions have found applications in a broad range of allowing their use as delivery systems, as stabilisers for fluid-in-
technologies and in the processing of various materials including fluid dispersions, and as building blocks in the design of
foods, cosmetics, paints, and drugs. Colloids (i.e. colloidal advanced materials.4–8
dispersions) as model soft matter systems are used to study There are several well-studied colloidal delivery systems.9–14
atomic systems.1–3 Nowadays often the term ‘nanodispersions’ Traditional examples such as liposomes, microemulsions, and
is used to describe nanosized (submicron) solid-in-liquid micelles are self-assembled systems from amphiphilic molecules
(nanosuspensions or nanoparticle suspensions) or liquid-in- such as block-copolymers, phospholipids or surfactants.15–18
liquid (nanoemulsions) colloidal dispersed systems. In consumer Nanosized emulsions are kinetically stabilised liquid-in-liquid
products, colloids (including nanodispersions) are either dispersions. Colloidal particles are usually in the form of solid-in-
naturally present, formed during the processing, or intentionally liquid or solid-in-gas dispersions. All these systems have been
added to tailor certain functional properties. Colloidal explored for oral drug delivery with different degrees of
dispersions have many attractive properties. One of the most success.10,19–21 Their applications in the areas of micronutrient
and nutraceutical delivery for the design of functional foods
Unilever Food & Health Research Institute, Olivier van Noortlaan 120, largely depends on the type of active molecule/ion and the
3133 AT Vlaardingen, The Netherlands. E-mail: krassimir.velikov@
unilever.com; eddie.pelan@unilever.com; Tel: +31 10 460 5068 product format (e.g. liquid, semisolid or solid). This paper
† Submitted as a contribution to the Soft Matter web theme on Food mainly focuses on colloidal particles and nanoemulsions as
Science. delivery systems for micronutrients and nutraceuticals.
Krassimir Velikov is a research Eddie Pelan is a director of the

manager in the Unilever Food Food Structural Design depart-
and Health Research Institute. ment at Unilever Food and
He conducted his PhD in the Health Research Institute in
field of soft condensed matter Vlaardingen, The Netherlands.
physics both in the FOM insti- He started at Unilever Colworth
tute AMOLF and in the Soft in 1985 in the Biosensor and
Condensed Matter group at Optical devices group. He
University of Utrecht under the obtained a PhD in Food Science
supervision of Prof. A. van in the area of Molecular
Blaaderen. Joining Unilever in Dynamics Simulation of
2002, he focused on design, sta- Competitive Adsorption from
bilisation and application of the University of Leeds. His
colloids for control of product broad expertise covers areas of
functionality and delivery of functional ingredients. His research food colloids such as tea cream, gels and emulsions.
interests further include colloid assembly and interaction with
biological systems.
1964 | Soft Matter, 2008, 4, 1964–1980 This journal is ª The Royal Society of Chemistry 2008
combination of these two effects, electrosteric stabilisation, is
also a widely used method. The stabilisers can be of different
nature ranging from small molecules to large polymers. They can
be attached by physical adsorption or chemical binding to the
particle surface (grafting). If the stabilisation is not sufficient,
instabilities like Oswald ripening or aggregation may occur.
These modifications also alter the wetting properties of the
colloidal dispersion which is important for their structuring and
Fig. 1 Schematic representation of top-down and bottom-up stabilisation properties.49
approaches for fabrication of colloidal dispersions. Colloidal particles are currently prepared from various mate-
rials with different shapes and morphologies.34,35,38 Due to their
ability to assemble in bulk and at (fluid) interfaces, they are

Colloidal dispersions can be produced using two general widely used in stabilisation of fluid-in-fluid dispersions and as
approaches (Fig. 1). In the first approach, called ‘‘top-down’’, precursors for advanced nanostructured materials, nano-
large particles or droplets are broken down to smaller ones using composites, and coatings.49 Nowadays the interest in these
mechanical energy. Examples of such processes are emulsifica- systems has been dramatically increased due to fast developing
tion22–29 and milling.21,30,31 Although close to the traditionally fields like novel materials and drug delivery. Many new materials
used processes and easy to implement, top down approaches can are now being formulated in the form of colloidal particles or
be very energy intensive and expensive. One obvious advantage dispersions. Colloidal particles can be made of the material of
of these methods is that the final composition is usually set from interest or from a mixture with a suitable matrix in which the
the beginning of the process. material of interest is encapsulated or embedded. Colloidal
The second ‘‘bottom-up’’ approach, currently rapidly devel- particles can have different internal structures ranging from
oping and widely used for fabrication of colloidal particles, has crystalline (e.g. nanocrystals, cubosomes50,51) to amorphous (e.g.
originated from traditional colloid chemistry where molecules, solid–lipid nanoparticles52 or polymeric nanoparticles). Cubo-
monomers or ions are condensed into a liquid or a solid phase somes are self-assembled liquid crystalline particles with
using a physical or a chemical process.10,32–35 Such approaches a nanostructure that provides unique properties of practical
are well developed today for condensation from gas or liquid interest like encapsulation.50,53
phases with good control of particle size, size distribution, and in Colloidal particles can be made with different morphologies,
some cases shape.35 including homogeneous spheres, core–shell type particles, and
Examples of chemical precipitation are the formation of hollow particles.34,35 Particle shape can also be controlled to
an insoluble salt between two ions, ion hydrolysation, or a certain extent, but this is usually a rather challenging task.4,54
(co-)polymerization in homogeneous solutions or in reverse Nanoemulsions, also called miniemulsions55,56 or sub-
micelles.34–38 Physical precipitation can be realised by changing micrometre-sized emulsions,57 are liquid-in-liquid dispersions
the solubility of material by changing the quality of the solvent with a small droplet size, typically in the range of 50–400 nm.58,59
(e.g. adding an antisolvent39,40 or a salt), using supercritical Nanoemulsions, in contrast to microemulsions, are not ther-
fluid-based technologies where the role of solvent or anti- modynamically stable. However, they can have high kinetic
solvent is a supercritical gas41–43 or removing the solvent from stability because of their small droplet size that makes them
a homogeneous mixture or dispersion (e.g. emulsion or aero- stable against sedimentation or creaming. Although nano-
sol).39 Alternatively physical precipitation can be achieved by emulsions have extreme Laplace pressures, of the order 10–100
forming insoluble complexes between (macro)molecules, as in atm, the droplets can remain stable against Ostwald ripening if
the case of coacervation.44–46 Combinations of these approaches the dispersed phase has very low solubility in the continuous
are also often used; e.g. mechano-chemical aproaches47 or phase. Alternatively, they can be stabilised by adding a second
physical precipitation followed by chemical cross linking.48 dispersed phase with very low solubility and/or incorporating
The bottom-up approaches typically require less energy and strongly adsorbing water-soluble polymers.60–62 Nanoemulsions
give better control of the particle formation. However, they have the advantage over microemulsions that a lower surfactant
may appear technologically more complex and difficult for concentration is needed for stabilization.
implementation at the current stage of production for many Nanoemulsions have found applications in cosmetics and
industries. As a result, the first approach chosen for formulation personal-care formulations,59,63–66 in agrochemicals67 and in the
of colloidal dispersions is often high energy milling or ultrahigh chemical industry for the preparation of latex particles,68,69 etc. It
pressure emulsification. The choice of process for the production was demonstrated that nanoemulsions can be used successfully
of colloidal delivery systems depends on many parameters, as drug delivery systems70,71 for oral,72,73 occular,74 parenteral75
ranging from specific properties of the material to cost and scale and transdermal76 administration. For many years, nano-
up restrictions. emulsions (e.g. Intralipids) consisting of soybean-derived
Introduction and stabilisation of colloidal dispersions in triglycerides and phospholipids from soybean or egg yolk have
complex soft matter systems is another challenging task. The been applied clinically for parenteral nutrition as an efficient
resulting colloidal particles or droplets in most cases can be energy source.
stabilised by providing enough surface charge to overcome the The methods using mechanical energy (e.g. high shear stirring,
strong van der Waals attraction or/and by using molecular high-pressure homogenization, ultrasound) are referred as to
stabilisers which provide a steric barrier to aggregation. The high energy emulsification methods,26–29,77 while those making
This journal is ª The Royal Society of Chemistry 2008 Soft Matter, 2008, 4, 1964–1980 | 1965
use of chemical energy stored in the components (methods based Table 1 Examples of common micronutrients and nutraceuticalsa
on phase inversion) are referred to as condensation or low-energy
Micronutrients Nutraceuticals
emulsification methods.78
In the phase inversion volume methods, water is added at Water soluble vitamins Polyphenols
room temperature to an oil solution of the surfactant(s) until Vitamin B1 (thiamine) Flavonoids
inversion to an o/w nanoemulsion occurs.79–81 In the second Vitamin B2 (riboflavin) Isoflavone
Vitamin B3 (niacin) Anthocyanins
low energy method the phase inversion temperature (PIT) Vitamin B5 (pantothenic acid) Conjugated Linoleic Acid
principle is used. Transitional inversion is induced at constant Vitamin B6 (pyridoxine) Omega-3 PUFA
temperature by changing the HLB number of the emulsifier Vitamin B7 (biotin) Terpenoids
system using surfactant mixtures. Alternatively, the temperature Vitamin B9 (folic acid) Alkaloids
Vitamin B12 (cyanocobalamin) Caffeine
of the emulsion system is increased until the interfacial tension Vitamin C (ascorbic acid) Theobromine
reaches a minimum value. At this temperature, very small Oil soluble vitamins Theophylline
droplets are produced. They are very unstable and undergo rapid Vitamin A (retinol, retinoids, Minerals
carotenoids)
coalescence, unless stabilised by rapid cooling of the system from
Vitamin D (ergocalciferol and Ca, Mg, Zn, K, Fe, Mn, Cu, Se
the PIT to room temperature.82 This approach however, as cholecalciferol)
pointed out by Mason et al.,27 does not always leads to true Vitamin E (tocopherol, Organic and inorganic salts of
metastable nanoemulsions. The last low energy method is tocotrienol) these minerals
Vitamin K (phylloquinone,
based on dilution of a microemulsion with an excess of one of the menaquinone)
two phases.83 Depending on the melting temperature of the a
material, it is possible to move from nanoemulsions to colloidal Some micronutrients also have nutraceutical action.
suspensions. Therefore, nanoemulsions can also be used as
a precursor for colloidal suspensions, formed as a result of
solidification of the nanoemulsion droplets. or supplements. Sources of minerals are inorganic or organic
One emerging area of application of colloidal dispersions is the salts, ranging from fully water soluble simple salts (e.g. CaCl2) or
design of functional foods.84 Functional foods are becoming complexes (e.g. NaFeEDTA) to sparingly soluble salts (e.g. ZnO,
increasingly popular among consumers as a result of increased FePO4, CaCO3).
knowledge of functional ingredients and their impact of human Nutraceuticals are not essential for human life, but they have
health and physiological functions. Nowadays the consumer a positive effect on overall health and prevent certain
would like to address several health problems like cardiovascular diseases.84,85 Nutraceuticals are often bioactive molecules or
health and obesity by using food products rather than drugs. The phytochemicals (Table 1). Phytochemicals or phytonutrients are
design of functional foods for the delivery of nutraceuticals and bioactive molecules derived from plants. The complete physio-
micronutrients is a big technological challenge. logical role of phytochemicals is not fully understood and a lot of
This paper presents the general concept of using colloidal research is devoted to reveal their impact on human health.
dispersions as delivery systems for micronutrients and nutra- Several minerals have also been recognized for their nutra-
ceuticals for functional food design with a specific emphasis ceutical potential.84 Among the most obvious are calcium, in
on control of product functionality: product composition, relation to bone health, colon cancer and perhaps hypertension
structure/texture, stability, taste/flavour, appearance, and and cardiovascular disease, and iron, in relation to mental
ingredient bioaccessibility and bioavailability. The specific development and anaemia. Potassium has been purported to
advantages in using colloidal particles and nanoemulsions as reduce hypertension and thus improve cardiovascular health.
delivery systems for micronutrients and nutraceuticals will be Several trace minerals have also been purported to have nutra-
discussed below. The application of colloidal dispersions will be ceutical potential; these include copper, selenium, manganese,
exemplified with the cases of delivery of reactive micronutrients and zinc. Their nutraceutical potential is usually discussed in
and poorly water-soluble nutraceuticals. At the end, the benefits relation to antioxidation. Copper, zinc, and manganese are
of using colloidal dispersions as delivery systems in functional components of certain enzymes while selenium is a component of
food design and the challenges to overcome towards application glutathione peroxidase. Certainly more investigation is required
will be summarised. in the area of trace elements in the light of their metabolic
relationships to other nutrients and the potential for toxicity.84
Micronutrients and nutraceuticals

Colloidal delivery systems: principles of use
The most common micronutrients are vitamins and minerals
(Table 1). They are essential for human growth and development, Product functionality is a complex product description that
but most of them are not produced in the human body and need covers formulation, structure, texture, stability, appearance,
to be supplied through foods and/or food supplements. Vitamins taste and flavour, and bioavailability of the ingredients. In our
are generally divided into two classes: water-soluble and attempt to design functional foods, we need to introduce the
oil-soluble. Their solubility and reactivity define some of the actives in a proper form to assure stability, as well as good taste
issues and possible restrictions for their formulation in foods. of the final product. Unfortunately, often nutraceuticals and
Minerals are another very important element for the human diet micronutrients cause problems due their own inherent (physico-
important for growth and health. Minerals are not produced by chemical) properties or due to interaction with other ingredients
the human body and they also need to be supplied through food present in the system. As a result, the food functionality is often
compromised. For example, formulation may not be possible,
due to solubility limitations, the texture or appearance being
changed, the physical or chemical stability being decreased, taste
being modified, and in some cases the bioavailability of the active
being adversely affected.
In general, there are two ways to introduce a functional
ingredient into a product: as a soluble or as an insoluble (i.e.
dispersed) component. Depending on the material’s specificity,
however, several problems can be encountered. To illustrate
some of these issues, consider the example of delivery of calcium
(Fig. 2). If calcium is introduced in a soluble form, e.g. by using
a soluble salt (such as calcium chloride), it is easy to formulate

a product by simple dissolution; the calcium form is bioavailable,
but it gives a bitter taste and causes stability problems due
to interaction with proteins, especially plant proteins, or with
Ca-sensitive biopolymers (e.g. pectin, alginate). On the other
hand when calcium is added in an insoluble form as large
particles, e.g. as calcium carbonate or phosphate, it may cause
abrasion of the processing equipment and sedimentation if
the product is liquid. A sediment on the bottom of the package
could be unsightly, and the calcium would no longer be available
for consumption. From this picture, it is easy to see that we need Fig. 3 Casein as an example of a natural colloidal delivery system for
a balance between solubility and dispersibility of the active calcium.86
ingredient. Furthermore, we need control over this balance in
order to have flexibility in solving technical issues. A generic
Ca2+ ions is very low). However, milk has good calcium
solution for these problems is the use of colloidal delivery bioavailability because of the small size and amorphous state of
systems, which are insoluble in the product but dissolve in the the calcium phosphate, which lead to quick dissolution in gastric
gastro-intestinal (GI) tract upon consumption. In addition, conditions (pH z 1–2). Unfortunately, there are no readily
colloidal dispersions are small enough not to cause physical available natural colloidal delivery systems for most of the
instabilities like sedimentation. common micronutrients and nutraceuticals, therefore design and
Colloidal delivery systems are in fact found in nature. Casein fabrication of custom-made delivery systems are required.
for example is a very illustrative case of a natural colloidal
delivery system for calcium (Fig. 3). In milk, calcium is cleverly
‘‘engineered’’ into porous casein colloidal particles of sizes Physico-chemical stability
smaller than 500 nm.86 From a consumer’s and product
formulator’s point of view, the calcium is in the form of colloidal The ability to control particle/droplet composition, size, and
particles of calcium phosphate, which does not compromise the surface properties provides several advantages in controlling the
taste (no bitterness typical for calcium), nor the physical stability physico-chemical stability of a product.
(as the particles are too small to sediment), nor the chemical
stability (no protein precipitation as the concentration of free
Physical instability
As already mentioned, colloidal dispersions can display
extraordinary stability against gravity driven phenomena
(creaming or sedimentation), particularly important for liquid
products, due their small particle size. For dilute systems, the
creaming/sedimentation rate is given by the Stokes equation
v ¼ 2r2(r r0)g/9h, in which r is the particle/droplet radius, h is
the viscosity of the continuous medium, r and r0 are the densities
of the dispersed and the continuous phase, respectively, and
g ¼ 9.8 m s2 is the acceleration due to gravity. From this
equation is seen that a tenfold decrease of the particle radius can
decrease the creaming/sedimentation rate 100 times. Further-
more, below a critical size the rate of creaming or sedimentation
can be sufficiently low, which for practical applications can be
approximately only 1 mm in 24 h, so that the system will not
Fig. 2 Schematic representation of possible issues encountered during display a visible creaming or sedimentation because of Brownian
formulation of micronutrients and nutraceuticals depending on the motion, caused by the fluid molecules, which redisperses the
manner of incorporation. The signs [ and Y indicate increase and particles in the liquid. More exact criteria can be set when the
decrease of the respective product functionality characteristic. gravitational energy gained by a particle sedimenting over
block-copolymers.92 The addition of antisolvent results in the
reduction of the ripening rate by dramatically decreasing bulk
solubility. The narrower the initial size distribution, i.e., the
smaller the difference between the higher-solubility small parti-
cles and the lower-solubility large particles, the more stable is the
dispersion. Ostwald ripening can also be due to mass transport
facilitated by micelles if the concentration of free surfactant is
above the critical micelle concentration.93–95 Although in most
cases considered an unwanted phenomenon, Ostwald ripening
has been used to design novel hollow colloidal particles96–98 and
for fine tuning of particle size.99
Other processes, such as flocculation and aggregation, can also

occur in colloidal dispersed systems. These however are linked
directly to the colloidal stability of the systems. In high concen-
trations, which are not typical for food products but usually only
Fig. 4 Calculated creaming rate v as a function of the droplet size r for in ingredient precursor systems, gelation could also take place
an oil droplet (r ¼ 0.91 103 kg m3) in water (r0 ¼ 1.01 103 kg m3, h due to physical arrest or due to attractive interaction between the
¼ 0.001 Pa s).
particles.100,101 In the presence of polymers, colloidal dispersions
are also susceptible to depletion induced instabilities that cause
a distance of one radius R becomes equal to the reduced phase separation and aggregation.102
temperature kBT.87,88
Fig. 4 shows the calculated creaming velocity of a droplet with
Chemical instabilities
a density r ¼ 0.91 103 kg m3 (a typical oil) in a liquid with
density r0 ¼ 1.01 103 kg m3 and a viscosity of h ¼ 0.001 Pa s. In general, chemical instabilities reflect the chemical nature of the
From the graph for practical applications the critical droplet individual ingredients and their ability to participate in chemical
radius for a typical oil-in-water emulsion is estimated at about reactions either alone or in the presence of other ingredients.
250 nm. Due to thermal fluctuations and mechanical fluctuations Oxidation and photo-induced oxidation are among the most
in practice even large droplets (<400 nm) will not show visible common problems in food formulations. The addition of
creaming. In the case of minerals (e.g. calcium carbonate) it is micronutrients and nutraceuticals could significantly complicate
more difficult to achieve stability against sedimentation because this issue. First of all, many nutraceuticals (e.g. antioxidants like
minerals typically have densities higher than 2 103 kg m3. polyphenols) and vitamins are unstable and undergo oxidation
The stability of colloidal delivery systems to gravity driven during storage (e.g. vitamin C). On the other side, micronutrients
phenomena can be used to design more stable products, with like the transition metals iron and copper play a very important
extended shelf-life and increased stability at ambient tempera- role in the oxidation process as catalysts.103,104
ture. In dry form, colloidal dispersions properly stabilised during The strategies for minimising oxidation in functional foods are
drying89 can be used in instant (hot) drinks with improved not straightforward. They range from the use of antioxidants to
dispersibility. special packaging and working in an inert atmosphere. In the
Ostwald ripening, an interfacial-energy-driven dissolution and case of minerals that can catalyse the oxidation process it is very
re-precipitation of solutes, is another issue associated with important to minimise their concentration in ionic form
nanoparticles and nanoemulsions. Due to low solubility in the (e.g. single ions or complexes). This is linked to the pH, presence
continuous phase, mass transfer occurs from smaller particles of other chelators (e.g. EDTA), and reducing agents which
and droplets to larger ones. Ostwald ripening is the process by determine their electrochemical potential and their ability to
which larger particles became even larger and the smaller participate in redox reactions. In the case of mineral colloidal
disappear.90,91 This process is a direct consequence of the Kelvin particles containing iron or copper, the oxidation process can
effect, which leads to C(r) ¼ C(N)exp(a/R), where C(r) is the still take place at the particle interface (see Fig. 5).105 To control
solubility of molecules of the dispersed phase near a droplet of this process, coatings and passivation can be used.
this phase with radius r. The bulk solubility C(N) corresponds to In the case of nanoemulsions one should remember that
the solubility of a particle with infinite radius (the dispersed smaller droplets will increase the total surface area and therefore
phase has a flat surface); a ¼ 2gVm/RT is called the capillary the rate of oxidation can increase. Discoloration is also associ-
length and Vm is the molar volume of the dispersed phase, g is the ated with unwanted chemical interactions (e.g. oxidation of
interfacial tension, R is the universal gas constant, and T is the carotenoids), or complexation (iron ions with various poly-
absolute temperature. In the case of colloidal particles, rapid phenols), and can be controlled by choosing less reactive or less
ripening is usually countered by surface passivation due to soluble forms of the ingredient of interest in the form of
adsorption of organic molecules. In the case of nanoemulsions a colloidal dispersion, so no physical instability occurs.
very insoluble compounds are added (if not present naturally in The major advantage of colloidal dispersions in relation to
the oil blends) in the dispersion to stop the process. oxidation is that they can provide an alternative way for using
Liu and co-workers observed and studied quantitatively the insoluble forms of the targeted micronutrient or nutraceuticals,
Ostwald ripening process of b-carotene nanoparticles with sizes which are typically more chemically stable. When encapsulated
of 100 nm stabilised by poly(styrene)-b-poly(ethylene oxide) in more inert matrices that are slowly digestible, colloidal
Fig. 5 Schematic representation of the photo-redox cycle of iron.
dispersions can compensate by increased total surface to ensure

that the targeted micronutrients and nutraceuticals are still
bio-accessible. Examples of this are choosing different minerals,
and chemically modified molecules to provide oil or water
solubility respectively. For example, encapsulation of ascorbil
palminate, an oil soluble chemical derivative of ascorbic acid, in
the solid cores of lipid nanoparticles leads to greater stability due
to a decreased rate of oxygen diffusion in the solid matrix.106 In
practice, in many cases a careful balance between important
product functionality characteristics is needed in order to find an
optimal solution which gives acceptable product functionality.
Texture
Nanodispersions can also find applications in the design and/or fine
tuning of product structure and in enabling new product formats. Fig. 6 Relative viscosity h as a function of the particle volume fraction f
Both nutraceuticals and micronutrients are used in relatively for ellipsoidal particles with different aspect ratio (d ¼ L/D) according to
low concentrations (typically less than 1 wt%), therefore their eqn (1) using b ¼ 1000.
applications for structuring can be limited. Nevertheless, the ability
to introduce functional ingredients in a product whilst preserving a homogeneous random network is inversely proportional to the
the desired textural properties is already very important. aspect ratio fgel ¼ 0.7/d.109 Although the control of particle shape is
In addition, this approach can be used in pre-formulation of the difficult, shape anisotropic particles are seen as promising building
ingredients into more convenient to use concentrates. blocks for tomorrow’s materials.4,110 Some minerals (e.g. iron
oxides, calcium carbonate, protein aggregates111) can form shape
Viscosity anisotropic particles. From nutraceuticals, sterol for example has
been observed only as large anisotropic crystals in oil phases.112
Shape anisotropic particles like rods and platelets can be used as
alternatives to biopolymers to increase viscosity or create gels at
sufficiently low volume fractions. Due to their anisotropy such Particle-based stabilisation
particles are much stronger viscosifiers than spherical particles at Particles can provide stabilisation of fluid-in-fluid dispersions by
the same volume fraction.107,108 For example, the relative direct absorption at the fluid interfaces and by providing
viscosity of a semi-dilute suspension of ellipsoidal particles with hindrance against coalescence.49 Colloidal particles however can
an aspect ratio d is given by eqn (1).107 Particles with higher also provide stabilisation without direct absorption. For
aspect ratio increase more the viscosity at the same volume example, particle-stabilized emulsions were found in the case of
fraction (Fig. 6). extremely hydrophobic, non-wetting particles due to strong
d2 36d6 3 L bonding to (like-charged) oil–water interfaces because of image
hr ¼ 1 þ fþ 2 f d¼ (1) charge effects,113 or in the ‘‘halos’’ effect114 where highly charged
15lnd 5p blnd D
nanoparticles segregate to regions near negligibly charged
Gel formation using rod-like particles also occurs at much lower microspheres because of their repulsive Coulombic interactions
volume fractions than for the corresponding spherical particles. in solution. Due to segregation around the negligibly charged
For example, the critical concentration for the formation of large particles, the small particles can stabilise the system and
turn it into a fluid. Although particle-stabilisation of emulsions is cosmetics, pharmaceuticals, inks and paints. In general, the
a well-known phenomenon,115–117 the availability of a large product appearance depends on product microstructure and
variety of functional colloidal particles reinitiated the interest in composition. The overall appearance of a product depends on
this field.49,118 the way that it interacts with visible light. Scattering largely
In principle, particle stabilisation offers several advantages determines the turbidity and ‘lightness’ or ‘darkness’ of products,
such as decreased levels of surfactant used or completely whereas absorption determines their chromaticity (colour). The
surfactant free emulsions and increased stability. Interestingly, degree of scattering by a dispersion or emulsion depends on the
besides increased surface rigidity and directly preventing the concentration of the dispersed phase(s), size, and complex
coalescence between droplets, colloidal particles offer a new and refractive index of any particles/droplets present, whereas the
very interesting stabilisation mechanism: particle zipping of the degree of absorption depends on the concentration and type of
interfaces.119,120 In this mechanism, particles can join, in a stable dyes and absorbing materials present. Here the possibilities to
configuration, two droplets by linking the two interfaces. This control the interactions with light both on a single particle/
renders the emulsion partially flocculated, but gives great droplet level and through the structure (or degree of order) of
stability against both coalescence and gravity driven instabilities particle assemblies in the whole system provides a great tool for
if the flocks create a space filling network. Probably the most appearance control.
attractive feature of particle stabilisation of emulsions, is the The light scattering by single particles is well understood and
possibility for formation of stable double emulsions.121 The fact mathematical models to describe it exist.126,127 According to the
that once absorbed, colloidal particles will require very high classical scattering theory, the scattering of a sphere with a radius
energy to detach from the fluid interface makes the formation of r and complex dielectric constant under illumination with a light
stable double emulsions possible. This is very difficult to achieve of vacuum wavelength l can be described analytically. The
with edible low molecular weight emulsifiers alone. Such double extinction (Qext), scattering (Qsca), and adsorption efficiencies
emulsions can provide a means for encapsulation of many (Qabs) are functions of the size parameter, x ¼ 2pnbr/l and
ingredients and active substances. given by126,127
2X N
Taste & flavour Qext ¼ 2

ð2n þ 1ÞReðan þ bn Þ;
x n¼1
Taste and flavour are crucial for the success of any food product. 2 X
N
(2)
Qsca ¼ 2 2n þ 1 jan j2 þjbn j2 ;
Changes in flavour are often linked to the inherited taste of the x n¼1
ingredients or to unwanted chemical interactions (e.g. oxidation). Qabs ¼ Qext Qsca ;
The possibility to control chemical reactivity through solubility
where nb is the refractive index of the background. The Mie
was already discussed. Colloidal dispersions here also offer
coefficients an and bn are complex functions with numerous poles
control of solubility and therefore control of taste. This is
in the complex plane. For non-absorbing materials Qext and Qsca
particularly easy to illustrate in the case of fortification with
are identical. The scattering cross section might exhibit a number
minerals. Often free metallic ions cause a bitter or metallic
of resonances for a given particle size; at these wavelengths
taste.122–125 Through careful choice of the mineral source, as
scattering is very efficient.
defined by product pH, ionic strength or complexing agent, the
With current advances in colloidal particle design, it is possible
concentration of free metal ions in the systems can be minimised
to make particles from different materials with more complicated
to ensure the least effect on the product taste. Calcium fortifi-
morphologies like core–shell or composite particles. The optical
cation with water soluble calcium chloride is known to cause
properties of such particles can also be described using exact
bitterness,124,125 however, an insoluble mineral like calcium
theories; for instance using the Aden–Kerker theory127 for core–
carbonate or phosphate is not bitter due to its very low solubility.
shell particles, or using effective medium approaches to describe
Regulation of taste can be achieved by a proper choice of
the effective dielectric properties of the composite particles. The
material: water soluble or water insoluble (which can be however
two widely used effective medium models are the Bruggeman and
oil soluble). Chemical stability which can cause off-flavour
the Maxwell–Garnett approximations.
formation can be addressed with chemical modification. For
example, this often can influence the solubility of the ingredient. 31 3eff 32 3eff
An example is the fatty esters of ascorbic acid which are more f1 þ f2 ¼0 (3)
31 þ 23eff 32 þ 23eff
stable in oil solution (or dispersion106). Application in oil free
products can be achieved using colloidal dispersions of modified 3eff 32 31 32
¼ f1 (4)
taste, and flavour stable chemical derivatives. The strategies for 3eff þ 232 31 þ 232
minimising oxidation of lipid, micronutrients and nutraceuticals
are based on increasing physico-chemical stability in the product The Bruggeman approximation (eqn (3)) describes the effective
but can vary depending on the chemical nature of the individual medium (with effective dielectric constant 3eff) as two randomly
compound. mixed species with dielectric constants 31 and 32, whereas the
Maxwell–Garnett equation (eqn (4)) considers one medium to be
the host (32) and the second is the inclusion (31).
Appearance
Eqn (3) and (4) allow us to increase the effective dielectric
Appearance is a very important factor determining the consumer constant of the dispersed phase by addition of finely dispersed
perceived quality of dispersion-based products such as foods, inclusions from a material with higher dielectric constant than
Fig. 8 (left) Water fortified with 62.5 ppm Vitamin E with 351 nm, 98
nm, 726 nm particle diameter, respectively. (right) Cryogenic trans-
mission electron microscopy of vitamin E nanoparticles.133
bioavailability and pharmacokinetics), high cost may be added,

or new legislation may be required.
Fig. 7 Calculated scattering efficiency Qsca as a function of the particle There are several physical approaches possible to achieve
size/wavelength ratio. transparency: the first one being refractive index matching. This
method however has several limitations such as strong temper-
ature dependence and restrictions on which materials can be used
oil. Since the typical droplet size in foods is in the order of a few
to achieve this. Using microemulsions (solubilisation) is a well-
microns, using nanoparticles of a few hundreds of nanometres
known approach but usually it suffers from the high levels of
allows the design of nanoparticle–oil composite droplets with
surfactants needed. Nevertheless this approach is used for
tuneable dielectric properties. The increase of the effective
ingredient pre-formulation.112,128–132 Decreasing the particle size,
dielectric constant will increase the scattering efficiency (Qsca)
often used for low volume fractions, is another approach. In this
of single droplets, which in turn will increase the multiple
case several colloidal systems can be used. Colloidal particles and
scattering that results in increased opacity and whiteness. Such
nanoemulsions offer an attractive alternative, since their design
particles allow even better control of optical properties on
can be achieved with low levels of surface active materials.
a single particle level.
For example, the introduction of the oil-soluble Vitamin E
To demonstrate the possible benefit of using colloidal
in a beverage product as a traditional emulsion is possible but the
particles, we will consider only the effect of particle size on the
large droplets will change the product appearance. Vitamin E can
scattering efficiency at a single particle level. Fig. 7 shows
be formulated as a nanoemulsion (Fig. 8)133 with small enough
a theoretical calculation of the scattering efficiency of a single
droplets to allow formulation of clear beverages at targeted
particle with complex refractive index np ¼ (1.45, 0.01) as
concentrations. The same authors also demonstrate that the
a function of particle size/wavelength ratio. If we take this ratio
resulting suspension can be dried and then redispersed without
equal to 0.5 (e.g. particle radius 200 nm and wavelength 400 nm),
aggregating the particles.
as the upper limit it can be seen that the scattering efficiency is
already one order of magnitude lower than for larger micron size
particles, for which this ratio is equal to 2.5. Further decrease Whiteness
of the particle size will rapidly reduce the scattering efficiency of
the single particles. Although complete analyses will require In many cases, we are looking for the opposite solution—to
knowledge about the particle size distribution and particle increase the whiteness of a product. In this case we need to
concentration, this calculation clearly demonstrates the choose the size appropriate to enhance the single particle
possibility of reducing the scattering of light in a dispersion by scattering and to increase, if possible, the particle volume
decreasing the particle size. fraction, to enhance the multiple scattering, which in turn will
increase the reflectance. In principle the product whiteness can be
controlled by creating an efficient multiple scattering through
Transparency
particle size and volume fraction of dispersed phases. The
Often this is required when an insoluble material is added to spectral reflectance (R) of a concentrated dispersion for visible
a product which is initially transparent or clear. Transparency is light by particles or droplets dispersed in a continuous phase in
usually defined by the amount of light that is able pass through first approximation is given by the Kubelka–Munk theory134
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
the product of thickness l. This is given by the Lambert–Beer law R ¼ 1 þ K=S þ K=SðK=S þ 2Þ, where K is the absorption
I ¼ I0exp(pr2NpQext(r,np)l), where Np is the number particle coefficient and S is the scattering coefficient of the dispersion.
concentration, Qext is the extinction efficiency. There are several The values of the scattering and absorption coefficients for
approaches to enable transparency. Obviously the first one is spheres are given by126,127 K ¼ 2Cabs and S ¼ 3/4Csca(1 g) 1/
a chemical modification to turn the material from an insoluble 4Cabs, where Cabs ¼ pr2Qabs and Csca ¼ pr2Qsca are the
into a soluble one. An example is fatty acid esters of ascorbic absorption and scattering cross sections of a particle or droplet,
acid, which turns Vitamin C from water soluble into an oil and g is the asymmetry factor.126,127 Knowing the exact wave-
soluble vitamin. This approach however has many limitations length dependence of the refractive indexes of the two phases,
since the functionality of the molecule may change (including Cabs, Csca and g can be calculated using the Mie-scattering
theory.126,127 For realistic predictions, the size distribution of the on product appearance. For example, ferric pyrophosphate is
dispersed phase should also be taken into account. More precise white whereas ferrous pyrophosphate is green.141 On the other
theories exist for describing the light propagation in strongly hand, if colour is desired, both material and size properties can
scattering media.135,136 be tuned. As is known, depending on the materials, optical
In some cases, addition of strongly scattering inert pigment properties can be greatly influenced by the particle size, as for
particles (e.g. titania) to the product is used. Using core–shell example in the case of colloidal particles from noble metals.142
particles or composite particles is another solution, which allows Colloidal delivery systems offer unique possibilities to deliver
particles to have optical properties close to those of a particle insoluble pigments both in aqueous and in oil phases. In
made entirely of the shell material, which is then used in low addition, oil-soluble pigments can be delivered in aqueous
concentrations (e.g. titania coated silica could have almost as systems and vice versa.143–146 The application of carotenoid
strong scattering properties as particles made of titania colloidal particles developed by Horn and co-workers is
alone).137–139 In the first case, the shell material will be chosen to a wonderful illustration of the effect of particle size on optical
have higher dielectric constant with a thickness sufficient to properties (Fig. 9).39,147,148 The b-carotene colloidal particles have
mimic the scattering as from a homogeneous particle made from a core–shell structure. The shell consists of an adsorbed gelatin
the shell material. In the second case, the inclusions inside the layer. The core of the particles consists essentially of regularly
composite particles will have a higher dielectric constant so they aggregated b-carotene molecules. In these aggregates either H- or
can increase the effective dielectric constant of the whole particle. J-aggregate morphologies prevail, depending on the precipita-
Often the first approach in enhancing the whiteness of tion conditions.147
products is the introduction of high dielectric colloidal particles Another approach in creating colour effects is by creating
of titania which increase the multiple scattering and therefore structures with two- or three-dimensional periodicity in the
whiteness.140 The spectral reflectance increases with the increase refractive index.150–152 Such materials strongly interact with
of particle concentration. Some minerals of nutritional value can electromagnetic radiation and are being exploited for control of
also be used for increasing whitening, but as mentioned earlier, spontaneous emission and propagation of light. A low tech
volume fractions might be too low to create strong whitening application of these structures, also widely encountered in
effects. nature, is for creation of structural colours. In the case of non
absorbing particles, such structures will reflect predominantly
light with certain wavelengths. If colloidal crystals are created
Colour
using monodisperse colloidal particles or droplets, depending on
The absorption properties of the delivery systems can often the volume fraction and particle size they will exhibit very
influence or intentionally be used to influence the product colour. pronounced angle-dependent reflection colours (Fig. 10). In
When the material absorbs light, due to its complex refractive the first approximation, this is given by the Bragg law lmax z
index, particles or droplets can be used as pigments. In order to 2O2/3r(3eff 3bsin2 q)1/2, where 3p is the dielectric constant of the
enhance the colour effect, the particle size should be small particles/droplets, 3eff is the effective dielectric constant of the
enough to minimise scattering which can decrease the colour system (see eqn (2) and (3)). However, as mentioned earlier, this
brightness. Usually, in physical terms this means that Qsca is difficult to achieve using nutraceuticals and micronutrients
Qabs. This approximation is usually valid in the case of small size alone due to their low concentration.
parameter x ¼ 2pr/l 1. Due to their strong size- and morphology-dependent optical
On the material aspect of colour, some micronutrients can properties as single particles and assemblies, nanoparticles and
be delivered in different forms which have different optical nanoemulsions offer great opportunities for fine tuning product
properties (e.g. ferric pyrophosphate can be used as a white iron appearance and for enabling novel products. Applying colloidal
source). It is important to choose one which has the lowest effect dispersions can make possible the fabrication of new products in
Fig. 9 Edible colloidal pigments containing b-carotene colloidal particles.39
always applicable, but it has been successfully used for phytos-
terols. Esterification of sterol with fatty acid to form a sterol ester
is currently used to increase the solubility of sterol in oils.156,157
First, in the case of pure actives, the decrease of the particles
size leads to significant increase of the specific surface area for
dissolution/solubilisation.19 The dissolution rate is often given by
the Noyes–Whitney equation derived for spherical geometry
dms SD xd 3Dm1=3

0 mS
2=3
md
¼ Cs ¼ Cs (5)
dt h V rhr0 V
where ms is the mass of solid drug at any time, D is the drug

diffusion coefficient, S is the surface area, C, is the solubility of
the drug, h is the diffusion layer thickness, md, is the mass of
Fig. 10 Theoretical calculation of optical reflection spectra of the (111)
dissolved drug at any time, r is the density of the drug, m0 is the
crystal plane of a hypothetical photonic crystal built from oil droplets initial mass of drug, ro is the initial particle radius, and V is the
dispersed in water. Calculations are done using the scalar wave approx- volume of the dissolution medium. From eqn (5), it is obvious
imation.149 that decreasing the initial particle size will lead to an increased
dissolution rate.159,160 For minerals, it means that they will
behave similarly to a soluble mineral salt. Indeed, experiments
different formats allowing some translucency or even complete
have shown that smaller particles of iron pyrophosphate and iron
transparency or delivering a desired colour. Finally, colloidal
phosphate can dissolve fast enough and provide as good
dispersions with tuneable particle size will allow their addition in
bioaccessibility and bioavailability as iron sulfate.161,162
products with different degrees of translucency without changing
the product appearance. This is especially important in coloured Similarly, in the case of lyophobic micronutrients and nutra-
products, where in order to preserve the product colour the ceuticals the solubilisation rate in bile micelles, which is impor-
particle size should be sufficiently small. Otherwise the strong tant for delivery into the cells, can be a rate limiting step. As the
scattering will decrease the intensity of the product colour. solubilization process, which is also an important process in
Importantly, by controlling and assuring physico-chemical many areas such as detergency, emulsion stability, drug and
stability as described earlier (minimisation of oxidation and flavour delivery systems, proceeds in a typical dispersed system,
complexation processes), product appearance can be preserved. the molecules from the dispersed phase transfer into bile micelles
in the aqueous phase. As a consequence of this transfer
a decrease in the emulsion droplet size is expected, as recently
Bioavailability
confirmed using monodispered nanosized emulsions.117
Bioavailability of functional ingredients is a rapidly growing Several possible mechanisms for oil transfer into micelles have
issue in the area of functional food design.153–155 The solubility been considered in order to predict the kinetics of solubilisa-
and membrane permeability of many drugs and bioactive tion.163–168 Two alternative pathways could possibly govern the
molecules are the two major factors that contribute to their solubilisation mechanism: a molecular pathway and a micelle
bioavailability upon oral administration.156–158 Often these mediated pathway. In the molecular pathway, oil molecules
materials are present as solid, often crystalline materials at room dissolve directly at the droplet interface into the aqueous phase,
temperature, primarily in the form of poorly wettable powders and then are taken up by the micelles. Both molecular diffusion
with grain sizes in the micro- and millimetre range. The low through the aqueous solvent and rate of micellar uptake of the
absorption rate of poorly water-soluble, and especially lipophilic molecule are the sequential steps controlling this pathway. In the
substances from the gastrointestinal tract is generally attributed second pathway, a direct detachment of the micelles at the oil/
to the poor solubility and wettability in gastrointestinal fluids. To water interface is necessary to take the oil molecules into the
understand and control bioavailability related issues, one first aqueous continuum. In the micellar-mediated pathway, several
needs to understand the complex physico-chemical reaction mechanistic steps may be involved in series, such as surfactant or
taking place during the digestion process. This is however an micelle adsorption and micelle desorption. In the case of ionic
emerging area and due to its complexity is not well understood. surfactants the molecular pathway has been proposed as the
Digestion involves several physicochemical processes such as dominant path,169–171 micelles could not adsorb easily at an oil
dissolution, emulsification, solubilisation, enzymatic reaction, interface due to electrostatic repulsion. The molecular pathway
precipitation and absorption, which can be influenced through will become increasingly inefficient for increasingly water-
product composition and structure. insoluble oils. It has been proposed that, at least for systems with
There are several common approaches to improve bioavail- nonionic amphiphiles, a micelle-mediated pathway is more
ability. Poorly soluble bioactive agents can in principle be likely.163,172 Very likely, in real lipid digestion, both processes
enhanced by the following technological manipulations: chem- may occur depending on oil solubility, which increases from
ical modification, reduction of size,19–21 hydrophilisation of tri- to monoglycerides, and the degree of ionisation of the bile
particle surfaces to improve the wettability in aqueous media, acids, which depends on pH and ionic strength.
reduction of the crystallinity of the substance, or changing the For example, the solubilisation rate of soy bean oil (as an
polymorphic form. The chemical modification approach is not example of an insoluble substance) was measured in the order of
a few nanometres per second.173 Therefore, it is expected that the process is not controlled by a purely bulk diffusion mechanism:
decrease of particle size will lead to an advantageous increase in neither in the form of individual oil molecules diffusing through
the rate of solubilisation of low soluble lipophilic compounds. water away from the drops, nor by diffusion of micelles which
Weiss et al. suggested that micelles enhance Ostwald ripening by carry the solubilised oil. This has been confirmed by Pena and
transporting oils from smaller to larger droplets, and that this Miller and by Todorov et al. using studied solubilisation rates of
process occurs simultaneously with solubilisation,94,95 which single oil drops in aqueous surfactant solutions.94,95,170 The
further contributes, causing smaller droplets to solubilize and droplet radius is more likely to play a role in the cases of smaller
disappear sooner from the broad size distribution. Pena and droplets, where it appears as a controlling variable in the oil mass
Miller also supported this explanation with theoretical calcula- transfer kinetics during solubilisation.
tions.174 This effect could explain the experimentally observed Another very important process for digestion is enzymatic
increase in average size, even in the absence of Ostwald ripening. activity in the gastro-intestinal tract. This is especially important
Ariyaprakai and Dungan recently demonstrated time- when the micronutrient or nutraceutical is delivered in a digest-
dependent solubilisation, monitored using light scattering, and ible matrix (e.g. oil/fat or protein). In some cases, the active itself
observed a decrease in average droplet size over time, in contrast undergoes enzymatic degradation (e.g. conversion of sterol ester
to what has been observed previously with polydisperse to pure sterol). Most enzymes are water-soluble and the reaction
emulsions.117 They confirmed that the rate at which the droplet involves water and a water-insoluble substrate that is part of
size decreased was independent of the initial droplet size. a large aggregate, like a micelle or an emulsion drop or
Following their theory, it is assumed that the solubilization particle.175 The process of digestion is very intricate due to
process is driven by the approach to the ultimate concentration the complex time dependent compositions and phase behav-
Ceq
mic of oil in the aqueous micellar phase at equilibrium, with the iour.175–177 Several mechanistic models have been proposed to
kinetics of this approach characterized by a mass transfer describe the action of lipase on oil hydrolysis.178,179 For the
coefficient keff.117 The value of keff is in turn determined by the hydrolysis of oils by lipase, at low enzyme concentrations, the
controlling mechanism(s) for solubilization, such as transfer of following model equation can be used to predict the rate of
oil across the emulsion droplet interface, diffusion of molecules reaction v for a wider range of substrate concentrations180–184
or micelles through the aqueous phase, or uptake rates of
molecules by micelles in the bulk water. The central rate equation Et S
vf 2 (7)
in this theory is given by117 b b1 at þ 1 þ S
dmi eq
¼ keff S ðiÞ ðCs Cmic Þ (6) where Et is the total active enzyme (mol m3), at is the specific
dt
total interfacial area (m1), S is the bulk substrate concentration,
Here, dm(i)/dt is the rate of oil transfer from droplets of size i, S(i) b and b1 are kinetic constants. From the values of the overall
is the surface area of oil droplet i, and Caq is the aqueous oil mean diameter d, the interfacial area per unit volume of the
concentration at time t. From this equation is clear that the oil–water mixture system was calculated using the following
surface area will play a key role in the solubilisation process. As equation at ¼ 6f/dp where f is the oil volume fraction. Here
seen from their experimental data (Fig. 11), even at 1 wt% again the total surface area, which is proportional to the particle/
surfactant, the emulsion droplet size changes very slowly.117 droplet size plays an important role in determining the rate of
The effective mass transfer coefficient is independent of the enzymatic degradation. The enzyme activities can be further
initial emulsion drop radius, which implies that the solubilisation enhanced if the oil is solubilised in micelles.185 For the latest
review on the effect of surfactants, both in water-in-oil
microemulsions (hydrated reverse micelles) and aqueous solu-
tions upon enzymatic processes see ref. 186. The effect of droplet
size on digestion and bioavailability has already been a subject
for some studies on fatty acids. The droplet size was found to
have a major effect on lipase activity during lipid digestion.187
Armand et al. for example found that varying the mean droplet
size or the triglyceride composition of emulsions affects their
hydrolysis rate catalysed by pancreatic lipase.188 Their findings
could help in preparing new emulsions for intravenous feeding,
especially for patients with a reduced digestive capacity.188,189
Amorphization and changing the polymorphic form are other
ways of enhancing solubility and optimising delivery of poorly
soluble food actives and drugs.190–192 It is well known that the
amorphous form of a material dissolves faster than the crystal-
line ones.191 Finding a route to regulating polymorphism is a
central challenge in the production of pharmaceutical materials,
Fig. 11 Surface mean diameters of nearly monodisperse hexadecane-in- food active ingredients and commercially important speciality
water emulsions (0.04 wt%) stabilised with Tween 20 as a function of materials. Similarly, there appears to be a big difference in
time in solutions of various surfactant concentrations. Initial droplet size availability between the amorphous and crystalline forms of
0.49 mm.117 minerals (e.g. ferric phosphate193). For example, when
amorphous ferric phosphate is used as the source of iron, growth Further decrease of the particles led to changes in particle
is normal, but if the crystalline form is used, results are identical solubility.19 The Ostwald–Freundlich equation ln S/S0 ¼ 2Mg/
to the case when no iron is used. Differentiation of the amor- rrRT gives the effects of particle radius (r), density (r), and
phous from the crystalline form uses citrate solutions that extract interfacial tension (g) on solubility, S, at temperature T. S0 is the
the amorphous form but not the crystalline form. This is also solubility of a flat, solid sheet (r / N). M is the molecular weight
described for analyzing some prepared diets.193 of the solid, and R the ideal gas constant. Theoretically, this
Very often the nanodispersion and polymorphic approach for effect is not substantial (S/S0 > 2), until the particles are small
poorly soluble bioactive materials can be used in combination.192 enough, well under 200 nm. Fig. 13 illustrates the calculated
When a colloidal suspension is prepared using top-down effect of particle radius on S/S0 for a hypothetical particle with
processing such as high-pressure homogenization, a required step a molecular weight of 414.71, an interfacial tension of 50, 75, or
of the process is initial melting (or alternatively melting and 100 dyn cm1, and a density of 1 g mL1.196
dissolving in an oil phase) of the bioactive material, followed by Another approach for delivery can be achieved using delivery
emulsification in the water phase and then cooling. When through direct cellular uptake.197–201 Direct particle uptake in the
a liquid/melt or a saturated solution is cooled a crystalline solid GI tract is a normal phenomenon.202,203 So far this approach has
or an amorphous glass may form depending on the nature of the only been exploited for enhanced or targeted drug delivery and
system and the conditions under which the solidification occurs therapeutics.204 There are three important mechanisms by which
(Fig. 12). The degree of supercooling the liquid can sustain upon particles may cross the epithelial cell layer (Fig. 14).197,205
lowering the temperature, controls the ultimate morphology and Endocytosis is a constitutive process observed in most
is strongly influenced by finite-size effects. The finite-size effects mammalian cells for the uptake of particles through enterocytes
are related to the formation of a critical nucleus size for and M cells in the small intestine. Generally it is a slow process,
crystallization, the increased surface-to-volume ratio of small resulting in the fusion of endocytocytic vesicles with lysosomes
crystals, the wetting properties of the liquid on the substrate, the containing high levels of enzymatic activity. Endocytosis can also
effect of finite size on the dynamics of the liquid, and other be receptor mediated, involving specific receptors, for example,
factors. Finite-size effects are often imposed by a matrix with Vitamin B12 is absorbed by this uptake mechanism.206 Recently
small pores, such as porous materials, but may also arise in Decuzzi and Ferrari studied theoretically the role of specific and
free-standing geometries such as thin films or nanosized droplets. non-specific interactions in the receptor-mediated endocytosis
The nanoscale confinement of nanoemulsion droplets can influ- of nanoparticles.207 The characteristic time and threshold
ence the kinetics of crystallisation (Fig. 12): crystallisation is and optimal radii for particle endocytosis were estimated as
retarded compared to the bulk sample, the melting point is a function of binding energy factor, bond elasticity factor, and
reduced, and also the crystal polymorphism can be affected. non-specific attractive/repulsive factor at the cell–particle inter-
The crystallization process in stable nanodroplets with face. The model reveals that the contribution of both non-specific
a narrow size distribution can be significantly changed.194 It has and specific interactions is equally important.
been found that the undercooling required to obtain crystalli- Peptides and other macromolecules may be absorbed by the
zation in such droplets is significantly increased (Fig. 12). intestinal epithelium through the same mechanism. Paracellular
Recently Sato et al. have demonstrated using synchrotron X-ray transport is another route for direct particle uptake using the
diffraction that trilauroylglycerol nanoparticles from nano- tight junctions that pass between the cells. There is considerable
emulsions of its melt having diameters of 42 to 120 nm reduced interest in the drug delivery area in paracellular transport.208
the melting and crystallization temperatures and increased the Typically compounds using this route should not be metabolized
transformation rate of a / b0 / b in comparison to crystals by the intracellular enzymes, and it may be susceptible to
formed in the bulk phase.195 This is explained by the fact that, in manipulation by absorption enhancers, which are able to ‘open’
nanoemulsions, each droplet must be nucleated separately and
the nucleation mechanism is shifted from heterogeneous to
homogeneous nucleation.
Fig. 12 Schematic illustration of the effect of droplet size on the crys- Fig. 13 Effect of particle size on solubility for hypothetical examples
tallisation in melts and supersaturated solutions. (S solubility at the surface of the particle; S0 intrinsic solubility).196
Fig. 14 Schematic drawing of mucus (MU) covered absorptive enter- Fig. 15 Areas of applicability of colloidal delivery systems.
ocytes (EC) and M cells (MC) in the small intestine. Lymphocytes (LC)
and macrophages (MP) from underlying lymphoid tissue can pass the
basal lamina (BL) and reach the epithelial cell layer which is sealed
by tight junctions (TJ). Possible translocation routes for NP are (I)
Application examples
paracellular uptake, (II) endocytotic uptake by enterocytes and (III) M
cells.197 In the above sections we considered different effects of colloidal
delivery systems on the several aspects of product functionality.
In practice, often they address more than one issue and offer
tight junctions and thus enhance the absorption by the para- a truly enabling technology for the design of functional foods.
cellular route. It should be noted however that the tight junctions For example, the delivery of iron in food products or supple-
represent only a very small part (0.1%) of the surface area of the ments is one of the most difficult problems.209 The enrichment of
intestine.197 food with iron itself is very important as it helps fighting iron
Finally, it should be noted that colloidal dispersions can be deficiency and anaemia, and also aids the mental development of
made with controlled size, composition and surface properties children and elderly people.210 The use of soluble iron salts like
that can be used in targeted delivery in case it is needed to (i) iron sulfate causes metallic off-taste, severe lipid oxidation and
enhance deposition or accumulation in the body, (ii) associate an complexation with other ingredients e.g. polyphenols that leads
active with a specific cell population, (iii) associate it with specific to unwanted colour changes. The use of strong, but still water
intracellular components in the GI tract, or (iv) to prolong the soluble complexes, like NaFe(III)EDTA typically improve the
association of an active within a specific location within the GI stability, but does not stop the long term oxidation nor the
tract. In general, targeting can be achieved by active utilisation of discoloration process (e.g. with polyphenols).211 On the other
specific interactions between particle and cell (attach surface hand, using insoluble iron salts such as iron phosphates, which
ligands) or through a passive approach by correlating physico- are available as large particles causes sedimentation in liquid
chemical and surface properties and anatomy of the target sites products and decrease of the bioavailability due to their slow
(e.g. electrostatic interactions). Active targeted delivery can be dissolution rate.
achieved by binding of conjugates with mucus glycoproteins or To address these issues, we developed a general approach
cell membrane glycoproteins or glycolipids; by binding of based on colloidal delivery systems that can give the right
conjugates with ligands which are present specifically at the balance between solubility and dispersibility. Colloidal particles
surface of certain cells (e.g. M cells), or by recognition by the are not soluble in water but in diluted acids, as in the stomach
conjugate of mucin glycoproteins secreted in specific areas where the pH goes down to 1–2. Secondly, some iron phosphates
(e.g. cancerous cells). have an acceptable white colour that allows much wider appli-
These very advanced approaches require very good knowledge cation in foods. Recently we developed a simple process for
about the physico-chemical properties of the targeted compound synthesis and characterisation of iron pyrophosphate stabilized
and its metabolism. Colloidal delivery systems are already with the aid of biopolymers which greatly enhances their product
necessary from the very beginning to design intravenous compatibility (Fig. 16).141 Most importantly, if colloidal particles
formulations in order to evaluate toxicity and absolute are used as delivery systems for micronutrients, biopolymer
bioavailability. These are clear examples where the delivery and stabilisation offers a route for a food grade fabrication.
formulation approaches couple with the in body functionality of The next example illustrates another major problem associated
the targeted compound. Colloidal dispersions as delivery systems with nutraceuticals, namely their low solubility in water and
may address all issues associated with solubility/absorption of limited solubility in normal oils. The first is a clear barrier for the
the targeted micronutrient or nutraceutical (Fig. 15). Their formulation of low fat products, whereas the second limits
application is still under development for the area of foods, but it the application in oil-continuous systems where partially soluble
is expected that this field will develop rapidly due to the growing materials tend to recrystallise into very large crystals.212 This
interest in functional foods, and in general in understanding the in many cases changes the texture of the product in an unac-
physiological role of food ingredients. ceptable way.
Fig. 16 Transmission electron micrograph of ferric pyrophosphate Fig. 17 Transmission electron micrograph showing stanol ester
colloidal particles.141 colloidal particles.
Plant stanols and sterols have very low solubility in water and Conclusions
limited solubility in oil, which makes the formulation of products
Colloidal dispersions (both solid-in-liquid and liquid-in-liquid)
containing them difficult. A particular problem when the sterol
are promising delivery systems for nutraceuticals and micro-
and stanols are dispersed in the oil phase is Ostwald ripening
nutrients for the design of functional foods. The expected
which leads to post-crystallisation. In this process, initially small
crystals dissolve and large crystals grow and become unaccept- benefits of using colloidal delivery systems are linked to the
ably large, changing the texture of the products. To resolve the possibility of controlling the solubility–dispersibility balance in
problem with the limited solubility of stanol in oil, fatty acid the product, their stability, and product compatibility via control
esters have been developed.213 of surface properties and particle morphology, and finally the
Stanol and sterol esters are soluble in oil, but their formulation possibility of altering the dissolution/digestion rate and
in low fat products can be difficult. For example, the very high bioavailability. Colloidal delivery systems are not readily avail-
hydrophobicity of stanol esters results in deposition of sterol esters able and there is need for specific product compatible delivery
on hydrophobic surfaces. This phenomenon can be observed when systems. Both bottom-up and top-down fabrication approaches
for colloidal particles are being explored; as for example for
a sterol ester macroemulsion is kept in a plastic container. Another
delivery of very reactive micronutrients like minerals and stanol
general problem when formulating emulsions is gravity induced
ester—an example of water insoluble nutraceuticals. As with any
instability (creaming). When the droplet size is large, the creaming
rate is considerable and it is necessary to use thickeners and new technology, colloidal delivery systems could face the
viscosifiers to delay the creaming. Coalescence is also a possible challenging requirements for novel processing, which in many
source of instability encountered in many macro emulsions. cases may require open innovation with suppliers or other
These problems can be solved or greatly reduced by decreasing companies. Furthermore, the cost in comparison to benefit and
the particle size of the stanol ester dispersions by forming performance needs to be evaluated in detail to assess the full
colloidal dispersions. As a result, colloidal dispersions from potential of this technology. Besides all their expected potential,
stanol esters may allow the formulation of products with custom designed colloidal delivery systems are still rarely used in
extended shelf life. Typically the particle size is below 500 nm and current food products. As for any new technology, it has to be
proven safe before use, and should have a proven benefit on
it depends on the stabiliser concentration and processing
which consumers can base their choice and acceptance.
conditions (Fig. 17). As expected, the colloidal suspensions from
stanol ester were found to be extremely stable. Their size and size
Outlook
distribution did not change over a period of more than three
months. The successful application of colloidal delivery systems in soft
There are already several patents covering the use of particles matter systems such as foods requires a broad knowledge of
from sterol and sterol esters214–219 disclosing the use of nanoscale molecular, ionic, and colloidal interactions in the product
sterols and/or sterol esters with particle diameters of 10 to 300 nm matrix, as well as knowledge of biological function and metab-
as food additives. According to the invention, these delivery olism of the targeted micronutrients or/and nutraceuticals. Since
systems promote more rapid absorption by the blood serum after these processes are not independent, for successful application in
oral ingestion in comparison with conventional sterols and sterol industrial products, an integrated approach is required. An
esters. This will certainly be further developed with increasing approach where the ingredients are pre-formulated in a way that
needs for affordable food products with blood cholesterol allows easy incorporation and stabilization in the product matrix
lowering activity. is likely to be most useful. This approach also requires linking the
in product and in vivo function of the delivery systems. In this 20 V. B. Patravale, A. A. Date and R. M. Kulkarni, J. Pharm.
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Food Science Web Theme Issue: Guest Editor: Professor Peter Fryer, University of Birmingham

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This paper was published in Soft Matter as part of the

Food Science web theme issue

Microstructure of fat bloom development in plain

Food structure and functionality: a soft matter perspective

Interfacial structure and stability of food emulsions as affected by protein–polysaccharide interactions

Direct observation of adhesion and spreading of emulsion droplets at solid surfaces

Colloidal delivery systems for micronutrients and nutraceuticals†

Introduction important properties is that we have a means to control their

Krassimir Velikov is a research Eddie Pelan is a director of the

ability to assemble in bulk and at (fluid) interfaces, they are

Micronutrients and nutraceuticals

a soluble salt (such as calcium chloride), it is easy to formulate

Other processes, such as flocculation and aggregation, can also

Fig. 5 Schematic representation of the photo-redox cycle of iron.

dispersions can compensate by increased total surface to ensure

Taste & flavour Qext ¼ 2

mission electron microscopy of vitamin E nanoparticles.133

bioavailability and pharmacokinetics), high cost may be added,

Fig. 9 Edible colloidal pigments containing b-carotene colloidal particles.39

dms SD xd 3Dm1=3

where ms is the mass of solid drug at any time, D is the drug

Pharm., 2005, 299, 167. Carrier Syst., 2004, 21, 133.

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