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Better Nutrients and Therapeutics Delivery in

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Food Eng Rev (2012) 4:114–123
DOI 10.1007/s12393-012-9050-3
REVIEW ARTICLE
Better Nutrients and Therapeutics Delivery in Food Through
Nanotechnology
Hande Kaya-Celiker • Kumar Mallikarjunan
Received: 5 September 2011 / Accepted: 16 February 2012 / Published online: 8 March 2012
Ó Springer Science + Business Media, LLC 2012
Abstract The efficacy of nutraceuticals or therapeutics is
primarily a function of their conserved biological activity
and availability. As changing the size of fabricated mate-
rials into nanoscale, the stability and the solubility of valu-
able nutrients can tremendously be improved; and their
effective and controlled delivery via nano-vehicles can be
provided. In this review, we addressed the latest approaches
for nano-encapsulation and entrapment of hydrophobic
bioactive molecules and other nano-vehicles that proved
their success in drug delivery applications and summarized
their applications in the food industry.
Keywords Food nanotechnology  Nano-encapsulation 
Nanoparticles  Therapeutic delivery
Introduction
Over the past few decades, the new advancements in science
and technology, notably biotechnology and more recently
nanotechnology, lead to improvements in food science dis-
ciplines. As it happens, the first look into nanoscience dates
almost 50 years ago, when quantum physicist Richard
Feynman made his lecture presentation entitled ‘‘There’s
Plenty of Room at the Bottom’’ at the annual meeting of the
American Physical Society in 1959. In his presentation, he
revealed the feature of nanoscience in which the character-
istics and behaviors of matter change when scaled down
into nanometer scale [25]. Thenceforth, advances in
H. Kaya-Celiker  K. Mallikarjunan (&)
Biological Systems Engineering, Virginia Polytechnic Institute
and State University, Blacksburg, VA, USA
e-mail: kumar@vt.edu
123
nanotechnology proved his vision in many fields including
medicine, agriculture, cosmetics, and food; and demon-
strated how physicochemical characteristics of nanosized
substances can change the texture, structure, and quality of
foodstuffs [11].
The National Nanotechnology Initiative (NNI) has
defined the nanotechnology as ‘‘the understanding and
control of matter at dimensions of roughly 1–100 nm, where
unique phenomena enable novel applications’’. Nanotech-
nology, therefore, refers to the techniques for designing,
fabricating, measuring, and manipulating matter at the
nanometer scale [59]. This emerging technology has opened
up a new potential in research and development in numerous
research fields together with the increased funding oppor-
tunities to study the individual molecules and the specific
intra- and inter-molecular interactions in which they take
part [56]. As an indicator, the Federal research funding for
nanotechnology has increased from approximately $464
million in 2001 to nearly $2.1 billion for the 2012 fiscal year
in the United States [59]. Correspondingly, this remarkable
economical impact of nanotechnology recognized by other
countries, and according to the international benchmarking,
European Union (EU) and Japan invested approximately
$1.7 billion and $950 million, respectively, in nanotech-
nology-related research areas followed by China, Korea, and
Taiwan with $430 million, $310 million, and $110 million
research investments, respectively, in 2008. USA was
placed second with $1.5 billion budget in 2008 [65]. In the
following 10–15 years, the global market of nanotechnol-
ogy incorporated products was estimated to worth $1 trillion
along with a need of 2 million workers to support nano-
technology industries worldwide [59, 64].
This delectable propagation of nanotechnology in a wide
range of products in vast areas like medicine, cosmetics,
aerospace, microelectronics, eventually, drew attention in
Food Eng Rev (2012) 4:114–123
food sector where the creation of new food products sat-
isfies the macro-level needs for structure, quality, sensory
appeal, texture, and safety at the same time as be a good
source of nutrient. The nanoscale measure, control, and
manipulation over food matter may help to understand the
biological and physical phenomena in complex multi-
component food systems, which in turn, may allow
improving macroscale characteristics [83].
Within the last decade, the public interest was turned
into consuming food offering added value. Foods enriched
with nutraceuticals and providing increased bioavailability
of added micronutrients is emerging as a new trend. It is
apparent that food industry is mainly driven by profitabil-
ity, consequently by consumer acceptance. For this reason,
food industry has also looked ahead to new technologies to
improve the shelf life, traceability, and sustainability
[11, 27]. Hence, it is not surprising that applications of
potential of nanotechnology in food industry have grown
tremendously in the last decade. The worldwide sales of
nano-food products reached up to $1 billion, and it was
estimated to grow up to $20.4 billion market by 2010
mainly condense in food processing, food ingredients, food
safety, and food packaging [1, 11]. Currently, up to 400
companies around the world are applying nanotechnolo-
gies including Kraft, Nestle, Unilever, Keystone, Heinz,
Hershey, etc. [11, 46]; apparently, this number will dra-
matically increase in the near future considering the rapid
proliferation of nano-food technology.
In fact, food being ‘‘the of Nature’s own nanotechnol-
ogy’’ is in not a new concept to nanoscience. For example,
milk proteins, caseins or lactoglobulins, and phospholipids,
have been used for many decades as emulsifiers and tex-
turizing agents in food production [53]. It is also known
that many food proteins, folding into their stable globular
structure, are formed on a wide range of length scales
changing between 10 and 100 nm in size, and most poly-
saccharides and lipids are linear polymers less than 2 nm in
thickness [11]. In other words, most of food-associated
entities are already in nanoscale. Thus, nanotechnologists
are hopeful on the development of enhanced quality and
safety in engineered food products, since targeted delivery
of bioactive compounds will be successful when carried
through foods that are already familiar to the human
digestive system. Besides, processing foods may cost to
lose some or all of the nutrients under harsh heat treatments
of pasteurization or canning; or processed foods may not
naturally contain nutrients like antioxidants at all. More-
over, adding antioxidants or other valuable bioactive mol-
ecules to those products with conventional methods may
encounter some difficulties because of the heat sensitivity
of those nutrients. Hence, nano-engineered products give
an opportunity to protect valuable nutrients against degra-
dation during manufacturing and storage [77].
115
Most of the nanoparticles used traditionally belong to
the group of colloids [75]. The field of food colloids is
depicted with the physical structure of multiphase food
systems as the convergence of molecules in various states
like emulsions, aerosol, foams, or gels [53]. Michael
Faraday’s colloidal gold dispersion (sometime in the eigh-
teen-fifties) is one of the earliest applications where colloi-
dal stability was achieved by molecular attraction between
particles through Van der Waals forces [24]. In colloidal
particles, steric stabilization can be achieved via adsorption
of surfactant or coating them with chemically bonded
molecules [24, 75]. The colloidal dispersions in most cases
are small particles surrounded by complex dispersion phase
[27]. The application of nanotechnology in food is mainly
concerns about the optimum utilization of those dispersion
systems, already present in food matrix, to deliver the bio-
active agent through liposomes, micelles, nanoparticles, or
nanotubes for effective nutrient and therapeutic delivery and
increased bioavailability. The fundamental mechanism for
the release of target components in a nanoparticle is very
similar to mass transfer in a spherical particle with unique
transfer characteristics [45]. Jo et al. [45] had described
mathematical models to describe the release of drugs
through an encapsulated nanoparticle and that can be
extended to explain food nanoparticles. The release of the
nutrient and therapeutic component (c) from the food matrix
generally follows Fick’s second law. The concentration
gradient of the spherical particles follows the form:
 2 
oc o c oc
¼D þ 2r
ot or 2 or
where c is the local component concentration at time t and
the distance r from the center of the nanoparticle, and D is
the diffusion coefficient of the component in the food
matrix.
The initial condition is
cðr; 0Þ ¼ c0
The boundary conditions are
   
oc1 V oc 3Vs oc
V ¼ ¼
ot Kp ot r¼R R or r¼R
cðr; tÞr¼0 ¼ finite
where V is the bulk liquid volume of the surrounding
medium, c1 is the concentration of the component in the
bulk medium, Vs is the total volume of the particles, and Kp
is the partition coefficient characterized by the concentra-
tion ratio of the concentration inside the particles to the
bulk liquid component concentration in thermodynamic
equilibrium.
The field of research in developing food-based nano-
encapsulated delivery systems is an emerging one. Hence,
123
116
in this review, we focused on the formulation of some
delivery vehicles such as casein micelles, a-lactalbumin,
liposomes, carbon nanotubes, chitosan, nanosized self-
assembled liquid structures, nanoparticles, and nanocochl-
eates, their properties and current applications in food
industry.
Casein Micelle
Casein is the major component of milk where it is present
in the form of large colloidal units with a mean diameter of
150 nm, called casein micelles. There are four main types
of casein as as1, as2, b- and r-casein, and all four types are
held together via hydrophobic and electrostatic interactions
[68]. Casein is usually prepared by isoelectric precipitation
of skim milk at pH 4.6, which later resolubilized with
alkaline salts using calcium, potassium, sodium, or mag-
nesium hydroxide to increase the pH 6.7 and spray-dried to
get caseinate [72]. The arrangement of the resulting protein
was explained by hydrophobic and electrostatic interaction
differences of polymerized casein monomers, which are
probably arranged in an order to retain the polar groups
bare to the medium to allow maximum interaction through
the ionic composition of the medium [72]. Still, the struc-
ture of the casein micelle has long been a research subject
and argument. Mostly, there is compliance for the main
features of casein micelle, even though the internal structure
has not yet been well understood. Basically, casein micelle
is composed of calcium phosphate clusters together with
different casein molecules where three members of casein
family, as1, as2, and b-casein, precipitate with alkali, and
r-casein is forming colloidally stable units by sterically
stabilizing the unit as an outer layer (Fig. 1). According to
Fig. 1 Schematic model of casein micelle (Adapted from [81])
123
Food Eng Rev (2012) 4:114–123
steric stabilization theory, the hydrophobic layer provides
impenetrable barrier against aggregation. Hence, all grow-
ing chains terminate and leave the casein micelle with a
stabilizing coat of r-casein [16, 17, 35–39, 81].
The most substantial characteristic of all micelles is that
they can entrap nonpolar molecules, which are not natu-
rally water soluble, to improve the solubilization and bio-
availability of food-derived bioactives, including lipids,
antimicrobials, antioxidants, flavors, and vitamins. This
unique property of micelles has long been studied for the
delivery of the pharmaceutical compounds [32], but their
use as carrier vehicle for nutraceuticals has yet been rec-
ognized [12]. In the literature, there are successful appli-
cations of microemulsions include encapsulation of
lycopene [71, 76] or omega-3 fatty acids [22, 44, 66], but
studies about casein micelle encapsulation of bioactive
material are very limiting. Therefore, a novel approach is
to use casein micelle for nano-encapsulation and stabil-
ization of hydrophobic nutraceutical substances in non-fat
or low-fat food products to increase the longevity in foods
as well, to increase their bioavailability. For instance, a
research group from Israeli used self-assembled casein
micelles, as nano-capsular vehicle for stabilization of
hydrophobic nutraceutical substances. Researchers have
used the fat-soluble vitamin D as a model hydrophobic
nutraceutical compound to utilize the self-assembly ten-
dency of bovine caseins [69]. Another promising study,
published in 2011, has shown the successful use of reas-
sembled casein micelles to entrap DHA molecules for
improved delivery in food products while keeping the
stability against oxidation [86]. Yet again, in another recent
study, researchers have described the self-assembling beta-
casein micelles encapsulating a natural phenol, curcumin.
They proved that the developed micellar nanostructures
can be used as nano-carrier system for hydrophobic ther-
apeutic agents such as curcumin by increasing the solu-
bility and bioavailability [23]. These studies show that
casein micelles, having a self-assembled system, are ideal
candidates for nutraceutical nano-encapsulation for
enrichment of food products (Table 1).
a-Lactalbumin
a-Lactalbumin is a small (MW 14,200 Da), acidic (pI 4–5),
Ca?2-binding milk protein, which takes part in biosyn-
thesis of lactose in the lactating mammary gland. a-Lact-
albumin has a high affinity Ca?2 binding site, which
makes it good model for the studies of calcium binding
effects on the interactions of proteins. Actually, strong
binding to calcium site increases the stability of a-lactal-
bumin by shifting the thermal transition to higher temper-
atures. The stronger an ion binds to the protein (Mg?2,
Food Eng Rev (2012) 4:114–123 117

Table 1 Examples of nanodelivery systems and targeted nutraceutical and therapeutic compounds
Type of delivery system Encapsulated compound References

Microemulsion Lycopene [71, 76]

Microemulsion Polyunsaturated fatty acids [22, 44, 66]
Casein micelle Vitamin D2 [69]
Reassembled casein micelle Omega-3-fatty acid [86]
Beta-casein micelle Curcumin [23]
Tripolyphosphate-chitosan microspheres Vitamin C [19–21]
Tripolyphosphate-chitosan Lipid droplets [40]
Linoleic acid modified chitosan nanoparticles Trypsin [55]
Alginate–chitosan microcapsules Glucose oxidase [82]
Liposome Protease [49, 50, 52]
Liposome Lipase [48]
Liposome Vitamin D [4]
Liposome Betacarotene [79]
Potassium chromate
Liposome Nisin [7, 18, 84]
Nanoparticle (NovaSOL)a Coenzyme Q10, Omega-3-fatty acids Aquanova
Nanoparticle (LycoVit)a Lycopene, Vitamin D3 BASF
Nanocochleates (BioGeode TM)a Omega-3-fatty acids BDSI
NSSL (Nutralease)a Coenzyme Q10, Phytosterols, Vitamins A, D, E, Nutralease
soy isoflavones, omega-3 fatty acids (DHA-EPA)
a
Examples of nanoparticles that are in market

Na?1, and K?1), the more prominent is thermal transition

shift. However, binding of Zn?2 ions onto Ca?2-loaded
a-lactalbumin decreases the thermal stability and results in
aggregate formation, which makes the protein prone to
protease hydrolysis [34, 62]. Partial hydrolysis of a-lact-
albumin with a protease from Bacillus licheniformis was
shown to cause gel formation, which is consisted of non-
branching, hollow strands with a uniform diameter close to
20 nm, similar to microtubular structure [43]. Hydrolysis
was needed to make the a-lactalbumin prone to self-
assembly. The building blocks for specific self-assembly
are formed by hydrolysis of the protein that self-assembles
Fig. 2 Schematic illustration of self-assembly of partially hydrolyzed
into micrometer-long nanotubes (Fig. 2). In the literature, a-lactalbumin and transmission electron micrographs of resulting
the role of Ca?2 addition on the self-assembly of partially nanotubes (Adapted from [28])
hydrolyzed a-lactalbumin, stability under different condi-
tions, controlled disassembly of the a-lactalbumin nano-
tubes, and analysis of hydrolysis products served as the protein gels; this makes them a good candidate to serve as
building blocks of the nanotube have been extensively gelation agent. Besides being strong, gel is reversible,
studied [29–31]. transparent, and most significantly can be disassembled in a
The a-lactalbumin nanotube is unique in the sense that it controllable way. The most particular characteristic of
is the only food protein nanotube. Graveland-Bikker et al. a-lactalbumin is its cavity, which can be used for encap-
[28] have summarized the possible applications of a-lact- sulation applications. The concept of continued release of
albumin in food and medical fields. Owing to their stiffness encapsulated ingredients over time has become more
and long linear structure, a-lactalbumin nanotubes can be important, especially in food and pharmaceutical industry.
used as thickener by increasing the viscosity of the product. Having a cavity of 8 nm diameter and controlled disas-
As well, the rheological and microstructural properties sembly property, a-lactalbumin nanotubes can serve as
allow them to produce stronger gels compared to other vehicles for nutrients- and therapeutics-specific targeting

123
118
and can easily be applied in foods and drugs since it is
simply a milk protein [28]. Above and beyond, we should
not forget the health benefits of a-lactalbumin upon con-
sumption. Studies showed that a-lactalbumin boosts the
immune system and possesses anticarcinogenic properties.
Sometimes it is added to infant feeding formulas to man-
ufacture products that more closely approximate breast
milk. It was also shown that a-lactalbumin can induce
apoptosis in tumor cells and possess bacterial activity,
which suggests that when this protein comes to milk, it is
not just as food but it fulfills many important protective
biological functions [33].
Liposome
Liposomes are bilayered, spherical polymolecular struc-
tures, mainly made of natural or synthetic surfactants like
phospholipids. Liposomes are formed by the self-assembly
of lipid molecules in an aqueous solvent in which they are
suspended [67]. The nanomeric versions of liposomes are
colloidal structures produced by adding process energy in
the form of sonication or extrusion, during mixing in an
aqueous environment to force the bilayer to form liposome
[58]. The basic component of all clinically useful lipo-
somes has been the phospholipid molecule. When mixed
with water, the amphiphilic phospholipid molecules pro-
duce a closed bilayer sphere to shelter their hydrophobic
groups into their lipophilic interior, while exposing the
hydrophilic head group in contact with the aqueous phase
(Fig. 3). Like micelles, the resulting closed sphere can
incorporate a wide variety of functional components in
their center [12].
The size of the liposomes typically varies between 20 nm
and a few 100 lm [12]. Stability of the liposomes largely is
determined by nature of the lipid molecules including rhe-
ological properties and surface charge, as well as the com-
position and concentration of the incorporated molecule
[78]. For example, surface charge can dramatically change
the functionality of the liposome by affecting the electro-
static interaction between lipid particles and with other
Fig. 3 Schematic illustration
of a formation and b electron
micrograph (Courtesy: [14]
of liposome)
123
Food Eng Rev (2012) 4:114–123
charged compounds that will be entrapped and that may lead
to disintegration of the built structure and consequently
unwanted release of arrested compounds. Hence, the
extrinsic parameters like pH, temperature, and ionic strength
and the intrinsic parameters like nature of phospholipids and
entrapped compound can considerably change the chemical
and physical stability of liposomes [78].
The ability to entrap, deliver and release of water-sol-
uble, lipid-soluble, and amphiphilic materials makes lipo-
somes an exciting opportunity for the food technologists to
utilize as nanocarrier systems. Taylor et al. [78] summa-
rized the formation methods of liposomes reported in the
literature and applications in both pharmaceutical and food
industry, especially in dairy products. For example, they
cited studies about the liposome usage in dairy products as
reducing the degradation of cheese curd structure via pro-
teolysis during ripening by protease entrapment with
liposomes [49, 50, 52]. In further studies, lipase entrapment
has been suggested to increase the cohesiveness and elas-
ticity, while reducing the firmness of Cheddar cheeses [48].
Apart from many other enzyme entrapment applications in
liposomes for controlled release of targeted enzyme, lipo-
somes have also been used to enrich the dairy products
with vitamins to increase their nutritional bioavailability.
Water-soluble vitamin D has been entrapped in multilayer
liposomes to study the recovery and stability change in
Cheddar cheese, and findings have demonstrated that
liposome entrapment protected vitamin D degradation via
increasing the recovery and stability [4]. In a more recent
study, Thompson et al. [79] have used liposomes prepared
from a milk fat globule membrane (MFGM) phospholipid
fraction to encapsulate hydrophobic beta-carotene and
hydrophilic potassium chromate to show that the advanta-
ges of liposomes prepared from MFGM-derived phospho-
lipids via microfluidization for the encapsulation of both
hydrophobic and hydrophilic compounds by improving the
entrapment efficiencies for both beta-carotene and potas-
sium chromate [79].
Antimicrobial efficiency of food preservatives encap-
sulated in liposomes has also been reported [58]. One of the
polycyclic peptides, antibacterial food preservative, nisin,
Food Eng Rev (2012) 4:114–123
has received more attention because of its broad inhibitory
spectrum against a variety of food pathogens and con-
taminants [58]. Encapsulation of nisin in phospholipid
vesicles has been studied to increase the availability of
nisin for long-term applications and to prevent loss of
activity since its free form is more prone to degradation or
deactivation. In the study of Benech and his coworker,
liposomes with purified nisin Z added to cheese milk prior
to renneting was resulted in improved stability and inhib-
itory action in the cheese matrix while protecting the
cheese starter from the detrimental action of nisin during
cheese production. At the end of the 6-month storage,
cheeses made with encapsulated nisin contained 90% of the
initial nisin activity [7]. In another study, Were et al. [84]
have investigated the effect of lipid composition on size,
stability, and entrapment efficiency of nisin and lysozyme
and concluded that it is necessary to get the optimum lipid-
antimicrobial combination for microbiological stabilization
of antimicrobials when embedded and dispersed in aqueous
phase. Other than nisin, encapsulation of pediocin within
phosphatidylcholine liposomes has also been monitored in
beef tallow and beef muscle. Researchers have reported
27.5 and 28.9% increase in the recovery of pediocin
activity in heated muscle and tallow, respectively, opposed
to other samples having free pediocin [18].
Some of the many applications of liposome encapsula-
tion have been summarized here (Table 1). Liposome
entrapment has been shown to stabilize the encapsulated
materials against adverse effects of environmental and
chemical harms, which, for example, are related with the
enzymatic activity, chemical and physical alterations in
surrounding like being exposed to extreme pH and tem-
perature conditions [58, 78]. There is a great potential for
further improvements in the utilization of those lipid ves-
icles to advance the food quality and safety, through
focusing on antimicrobial entrapment.
Chitosan
Chitosan is a naturally ocurring amino-polysaccharide
created by alkaline deacetylation of chitin extracted from
shells of crabs, shrimps, and krills [8]. The main improve-
ment in this polymer over chitin is that it is soluble in
various acids solutions and available for chemical reactions
with acids to form salts using their amino groups with a high
charge density [80]. The other advantageous properties of
chitosan include its biocompatibility, positive charge, mu-
coadhesiveness, and its degradation into amino sugars [8].
Agnihotri et al. [2] have reviewed the chitosan-based micro-
and nanoparticle preparation methods, including emulsion
cross-linking, complex coacervation, ionic gelation, iono-
tropic gelation, emulsion droplet coalescence method, and
119
reverse micellar method. Researchers have, as well, listed
the possible chitosan-based particulate systems in pharma-
ceutical and biomedical applications in which the controlled
and sensitive targeting was achieved when used as drug
delivery vehicles. Generally, majority of the reported
studies focused on the optimization of process parameters to
arrange the release kinetics of the bioactive compounds
from chitosan, including the extend of cross-linking,
molecular weight of the chitosan, and physicochemical
properties of the drug, as well as the pH, polarity, and
presence of enzymes in the dissolution media [2]. Suc-
cessful results of those drug targeting studies prove the
potential use of chitosan as the delivery vehicle for thera-
peutics. For example, encapsulation of vitamin C with
cross-linked chitosan by spray-drying method has been
demonstrated [19–21]. Moreover, chitosan-coated lipid
droplets [40, 51] and enzymes immobilized on chitosan
nanoparticles [55, 82] were investigated (Table 1). Even all
of these studies are at laboratory level, it would be fair to
contemplate that chitosan-based nanoparticles might be a
good candidate to be used as nutraceutical carrier, as well,
to improve the bioavailability of the material consumed
upon foods for future industrial applications.
Carbon Nanotubes
Carbon nanotubes are well-ordered carbon allotropes of
high aspect ratio with high surface area, which lengths
from several hundred nanometers to several micrometers
with diameters of 0.4–2 nm for single-walled (SWNT) and
2–100 nm for multiple-walled (MWNT) carbon nanotubes
(Fig. 4). They are viewed as ‘‘rolled up’’ structures with
one or more layers of graphene sheets, which increase their
mechanical strength and thermal and chemical stability
[54]. From the time when first successful SWNT and
MWNT synthesis were demonstrated [42], researches have
been directed toward their potential for bioapplications via
functionalizing their surface for increased solubilization
since raw carbon nanotubes have highly hydrophobic sur-
faces and are not soluble in aqueous solutions [73]. Several
researchers have reported successful functionalization
reactions for SWNTs and MWNTs; however, to be effec-
tive for biological applications, carbon nanotubes need to
be solubilized in aqueous media, which will allow for
exploration of their interactions with biological compo-
nents including mammalian cells [56, 74].
Grafting bioactive compounds by means of either con-
trollable immobilizing via functionalization reactions or
adsorbing onto the surface nanotube structures provide
improved immunological properties of functional groups
and envisaged broader applications including delivery of
drugs, proteins, vitamins, or minerals [9, 54]. Apart from
123
120
Fig. 4 Schematic presentation
of single-walled (SWNT) and
multiple-walled (MWNT)
carbon nanotubes (Adapted
from [85])
their function for sustainable release of therapeutics
through targeted cells in medicinal applications, recently,
Kang et al. [47] have shown that highly purified SWNTs
can show strong antimicrobial activity by destructing the
cell membrane when in direct contact with SWNT aggre-
gates. Application of using SWNTs as building blocks for
antimicrobial materials opens a new opportunity for carbon
nanotubes to be utilized in food safety arena. Successful
developments in increased solubility in aqueous media of
carbon nanotubes have also shown the significant potential
for use of carbon nanotubes in food systems, especially if
tailored to have efficient and fully controllable release of
flavors and nutrients. Even carbon nanotube delivery
applications are highly expensive to be used in food
industry, new developments for more available production
of functionalized carbon nanotubes can find acceptance in
food market as increasing the interacting surface area of
embedded material with the tongue and creating unique
sensory response [15, 41, 60, 63].
Nanoparticles
Nanoparticles can be prepared by two basic approaches,
either by ‘‘top-down’’ approach, where nanoparticles are
produced by means of physical processing of food mate-
rial; or by ‘‘bottom-up’’ approach whereby nanoparticles
are produced via self-assembly and self-organization of
small molecules [1]. The general approach is to apply both
approaches to produce nanoparticles for improved avail-
ability in human body. Thus, the efficacies of active
ingredients such as phytochemicals, vitamins, nutrients, or
minerals are aimed to be preserved against destructive
conditions as those bioactive compounds are consumed
orally and absorbed through digestive track and the small
intestinal walls [13].
123
Food Eng Rev (2012) 4:114–123
For food applications, forming nanoparticles of valuable
ingredients with a proper particle size has been studied
well, and actually some of them have already taken place in
the market. For example, a German company, Aquanova,
has developed a new technology, NovaSOL, which utilizes
the nanotechnology to produce nanosized materials to
prevent oxidation in oil and fats. With this technology,
valuable ingredients including coenzyme Q10, omega-3
fatty acids, vitamins, food colors, preserving agents, or
plant extracts can be introduced into food and beverage
products easily and effectively (Table 1). The micelle
product is a nanoparticle with a diameter of approximately
50 nm, providing clear solutions that is both water- and
fat-soluble. Micellation of active substances provides
increased penetration and intestinal resorption, as well as,
thermal, mechanical, and pH stability for the processed
ingredient. This innovation turns over a new opportunity
for solubilization enhancement of previously unprocessable
substances [3].
Another German chemical manufacturer, BASF, has
marketed nanoscale synthetic lycopene, LycoVitÒ, as a
food additive for beverage and food applications (Table 1).
This product can disperse in cold water, and it is proper for
beverages like fruit nectars and for food products like
cereals, nutrition bars, and baked goods. Carotenoids are
antioxidants and are converted into vitamin A in the body.
Nanoscale carotenoids, according to BASF, are more easily
absorbed by the body and increase product shelf life
(BASF [6]. The company, also, works on the vitamin D3
and omega-3 fatty acid formulations (Dry n-3Ò) to offer
consumers enriched foods (BASF [6].
Nanocochleates
Nanocochleates are stable lipid-based carriers, formed by
interaction between negatively charged lipid (e.g.,
Food Eng Rev (2012) 4:114–123
Fig. 5 Schematic illustration of drug delivery via nanocochleate
technology (Courtesy: BDSI [10])
phosphatidylserine) and cations (e.g., calcium) and have
cylindrical shape with multilayers composed of continuous,
solid, lipid bilayer sheets spinning as a spiral (Fig. 5). This
structure does not allow any internal aqueous space, yet
they are more stable than aqueous structures such as lipo-
somes. They have been used as vehicles to deliver bioac-
tive agents that are poorly absorbed by the body [84].
BioDelivery Sciences International has developed nanoc-
ochleate delivery system, namely BioGeode TM, which
is based on micronutrient-loaded oil droplet formed by
crystallization of soy-derived phospholipids and calcium
(Table 1). The crystalline structure of the nanocochleates is
reported to create a stabilizing matrix in which the
micronutrients are protected from the extreme conditions
of food manufacturing and storage (BDSI [10]. This
innovation demonstrates that the distinctive structure and
properties of nanocochleates make them excellent candi-
dates for controlled and systemic release of antioxidants
and other sensitive compounds without affecting the color
or taste of food [57].
Nanosized self-assembled Liquid Structures
One of the useful applications of ‘‘bottom-up’’ approach is
the fabrication of the molecular self-assembly of biomateri-
als. Nanosized self-assembled structures have many potential
uses because they possess both hydrophilic and hydrophobic
features, thus providing formation of mono- or bi-continuous
networks [5]. The nanosized self-assembled concentrates
(composed of water, oil, and surfactant) are capable of sol-
ubilizing large amounts of lipophilic and hydrophilic food
additives or drugs, thereby enhancing thermodynamic sta-
bility and bioavailability by protecting the bioactive agent
from manufacturing conditions (high heat, temperature, and
pressure) and throughout the shelf life [26].
A milestone application of nanosized self-assembled
liquid structures, NutraLease, offered another sight of the
121
potential use of nanotechnology on physiology (Table 1).
NutraLease demonstrated the incorporation of nutraceuti-
cals in the nanoliquid vehicles that are expanded micelles
(hollow spheres made from fats, with an aqueous interior),
with a diameter of approximately 30 nm (NutraLease
NSSL [61]. NutraLease has developed the formulations
for ingredients such as coenzyme Q10, phytosterols, vita-
mins A, D, E, and soy isoflavones. A new formulation of
omega-3 fatty acids (DHA-EPA) is in the final stages of
development. Increased solubility of the incorporated
nutraceuticals makes them more available for absorption
when widely distributed in the gastrointestinal tract as
small droplets. One of many food companies in Israeli is
Sherman Industries that has adopted this technology to
deliver Canola Activa oil, which is claimed as reducing the
cholesterol intake into the body by as much as 14 percent
by competing for bile solubilization [70].
Final Remarks
In the last half of the century, nanotechnology has reached
to a greater extent in many fields as is in food science. There
are many challenging factors as the food compound enters
to digestive system as it is exposed to severe conditions in
gastro-intestinal tract, leading to loss of some or all nutri-
tional value of food stuff. Changing size of materials can
change their uptake via improved absorption with nano-
particle systems through increased rate of release or simply
since nanoparticles can go where other large particles
cannot. Thus, the general approach has been to develop
nanoscaled vehicles from food-based compounds as being
‘‘the of Nature’s own nanotechnology’’. When tailored,
designed nano-structures have shown many advances
allowing to carry off naturally water- or fat-insoluble
nutrients to blood system and make them available to the
cells. Large collection of the literature evidences prospects
the upturn in nano-vehicle applications in food industry in
following decades. With the advances in nanotechnology,
variety of food products with promising functionality can be
expected to reach the market. Initial market success stories
can be expected to come from juices, dairy products, health
bars, infant formula, and chocolates.
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