Improving the Delivery System and Bioavailability of Beverages Through Nanoencapsulation

IMPROVING THE DELIVERY SYSTEM AND BIOAVAILABILITY OF BEVERAGES THROUGH NANOENCAPSULATION

10

Ida Idayu Muhamad, Dayang Norulfairuz Abang Zaidel, Zanariah Hashim, Nor Azizah Mohammad, Noor Fadzilah Abu Bakar Food and Biomaterial Engineering Research Group, Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, Johor Bahru, Malaysia

10.1 Introduction Food industry especially in food processing and the development of new food products is continuously looking for cheaper and more efficient methods to maintain the nutritional quality, functionality, and shelf life of the products. In this case, nano-engineering can be a promising tool for food manufacturing due to new advances such as in encapsulation and filtration techniques (Cerqueira et al., 2017). In this chapter, there is a focused discussion on nano-encapsulation in the beverage industry for its purposes and the types and methods. The varieties of formulation of nano-encapsulation with association colloids are also discussed in this chapter such as liposomes, solid lipid particles, dispersed liquid crystal systems, and nanoemulsion with protein, polysaccharides, and protein-polysaccharides assemblies. The availability of the bioactive compound/functional properties of nano-ingredient in beverages such as proteins, unsaturated fatty acids, vitamins, and minerals is also discussed. Next, the physicochemical, the release properties, and bioavailability in gastrointestinal (GI) digestion of nano-capsules as delivery systems in the beverage industry are explored. The positive impacts of beverages with nano-ingredient on human health and safety issues and challenges of beverages with nano-ingredient are also taken into account.

Nanoengineering in the Beverage Industry. https://doi.org/10.1016/B978-0-12-816677-2.00010-7 © 2020 Elsevier Inc. All rights reserved.

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10.2  Nano-Engineering in Beverage Industry Nano-engineering is a multidisciplinary field that comprises a massive range of processes, materials, and applications which deals with physical, chemical, biological, engineering, and electronic sciences (Handford et al., 2014). Nano-engineering is also one of the convincing technologies to enhance the food industry with conventional method. The word “nano” is defined as something small, tiny, and atomic in nature (García et  al., 2010). The application of nano-engineering on the food materials has generated vase opportunity for a new food creation with high performance to give serious influence of food manufacturing, packaging, and storage. Nano-engineering in the food industry includes the use of nano-sized ingredients and nanotechnology during the preparation and processing of the food product. The applications of nano-­engineering in the food industry are primarily focused on food packaging, food supplement encapsulation, development of sensors, and boosting the crop growth. The food processing and packaging assisted by nano-engineering has shown its capability in the food applications (He and Hwang, 2016). Traditional food materials also benefit from nano-engineering in terms of their mechanical strength, conductivity, and ability to integrate and deliver active substances efficiently at economical cost with environmental friendly solutions (García et al., 2010). In addition, nano-engineering can enhance the bioavailability of bioactive compounds such as antioxidants, vitamins, polyphenols, unsaturated fatty acids, and others (Cerqueira et al., 2017). This can be achieved through nano-encapsulation, one of the techniques in nano-engineering. Nano-encapsulation helps improve the taste, creates hygienic storage for food, and reduces the use of fat, sugar, and preservatives. The encapsulation can enhance the bioavailability of the active substances by the sustained release besides controlling the stability of the core material against diverse temperature, UV, moisture, and oxygen conditions. In these cases, liposomes, micelles, or protein-based carriers are used to nano-encapsulate the substances. Fresh food is known to have short life span as they are easily contaminated by microorganisms. The growth of microorganisms can be slow down by incorporating various types of active substances resulting in extended shelf life of the food (Ariyarathna et  al., 2017). The nano-­ carrier systems are used to protect the taste of certain ingredients and additives and to prevent them from degradation during processing (Chaudhry and Castle, 2011). Fig.  10.1 summarizes the benefits of nano-­engineering applications in the food and beverage industry. In order to incorporate bioactive compounds in the beverages, the solubility and delivery system should be comprehended. Various studies are necessary to design and improve the quality of the functional

Chapter 10  IMPROVING THE DELIVERY SYSTEM AND BIOAVAILABILITY  303

Fig. 10.1  The benefits of nanotechnology applications in the food industry.

beverages products. For example, identification and quantification of bioactive compounds, the proper dosage and delivery systems establishment to incorporate the bioactive compounds into beverages, absorption analysis, incorporated ingredient bioavailability, safety of bioactive compound incorporated beverages, the storage stability studies of the product, and possible interaction between bioactive compound and food component to provide safer and more effective functional food production (Recharla et al., 2017). Nanoparticles (NPs) have been widely known for health application ingredients, commonly used as supplements to maintain the nutrients needed in the body such as minerals, silver, calcium, magnesium, and others. It is also used as antibacterial, antiviral, and antimicrobial supplements. Increase number of researches have been reported on nanotechnology in various food applications (Fig.  10.2). Though research is still ongoing on their potential effects to the environment and human health, NPs have been progressively merged into consumer products. Nanotechnology Consumer Products Inventory (CPI) was created to record the marketing and distribution of nano-enabled products commercially. In 2015, there are a total of 1814 nano-enabled products by 622 companies in 32 countries with the majority of products are from The Health and Fitness category. The Health and Fitness category contains the most products (42%) and silver as the most frequent nanomaterial (24%). However, 49% of the total products do not supply the information of nanomaterial composition while 29% of the products contain nanomaterials dispersed throughout diverse liquid media (Vance et al., 2015). The global market value of NPs in general has ­commercially ­increased

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11000

300

10000

Number of publications

Number of publications

9000 8000 7000 6000 5000 4000 3000 2000

200

100

1000 0

0

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Year

(A) Nanotechnology

70

60

60 Nutrition

Agriculture

Number of publications

Number of publications

Year

(B) Nanotechnology and food

70

Food

50 40 30 20 10 0

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Food packaging

Food processing

Food production

Food safety

50 40 30 20 10 0

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Year

(C) Nanotechnology and agricultural related applications

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Year

(D) Nanotechnology and food related applications

Fig. 10.2  Number of nanotechnology publications per year in the Scopus database using key terms as indicated (A) nanotechnology, (B) nanotechnology and food, (C) nanotechnology- and agricultural-related applications, (D) nanotechnology and food-related applications (Handford et al., 2014).

from 125 million USD to 12.7 billion USD in 2000 to 2008, respectively, and is expected to reach about 30 billion USD by the end of 2020 (Goswami et al., 2017). Additionally, according to a survey, huge profit is expected toward the economy because the total market would reach a total of US$5.8 billion with US$1303 million from food processing, US$1475 million from food ingredients, US$97 million from food safety, and US$2.93 billion from food packaging in 2012 (Chellaram et al., 2014).

10.3  Nanoencapsulation Techniques in Beverages Industry This section describes the processes used to produce dispersed association colloid delivery systems, including nanolipid carriers, ­nanoliposomes, nanohydrogels, and nanoemulsions. Fig.  10.3 illustrates the different types of nanostructures with association ­

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a) Nanoemulsion

c) Nanolipid carrier Lipophilic surfactant

Hydrophilic surfactant

Amphiphilic surfactant

b) Nanoliposome

d) Nanogel Aqueous phase

Oil phase

Bioactive compound

Fig. 10.3  Different nanostructures with association colloid for beverages application.

c­ olloid for application in beverages that shows the linkages or absorption types of the different nanostructures.

10.3.1 Nanoliposomes A bilayer spherical structure having lipid material to entrap hydrophilic and lipophilic active compound will form an association colloids called liposomes. The lipid bilayers could be produced by phospholipids, sterols, glycerides, and also mixtures of other surface active materials composed of negatively charged and positively charged surfactants. Nutraceutical products in nanoliposomes vehicle provided high bioavailability and absorption, hygienic and comfortable injections, stability against harsh environment along the gastrointestinal tract (GIT), improved intracellular delivery, both hydrophilic and hydrophobic of active compounds, alternative form of tablet, and the same effect by taking a low dose (Shade, 2016). Liposomes structure can be form by self-assembly of amphiphilic lipids in aqueous solution. Amphiphilic lipids can be formed and located at interior aqueous phase, which act as a medium or pool for encapsulation process of hydrophilic compounds. Moreover, a lipophilic environment obtained from lipid bilayers rather than its liposomal core. Liposomes have dual function when come to process of encapsulation and stabilization of hydrophilic compound in their core while hydrophobic compound in the lipid bilayers (Emami et al., 2016). The formation of liposomes in nanometer size is termed as nanoliposomes.

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There is a similarity between liposomes and nanoliposomes on their physicochemical properties, however, more advantages and benefits are owned by nanoliposomes including serve a high surface area and better penetration potential as well as their manufacturing process provided more fresh surface area which means more high input of energy is required. According to most recent research, nanoliposomes could achieved the size range from 50 to 150 nm. Unfortunately, both liposomes and nanoliposomes are not thermodynamically stable. Hence, Liu et al. (2015) have exposed some problems during their fabrication process such as the destabilization of liposomes; degradation of encapsulated materials; the effect of environmental variable sincluding composition, storage temperature, and pH; the nature of the encapsulated materials, ionic strength, and revelation to light and oxygen. Nanophytosomes are a modern nanovehicles, initiated and enhanced from nanoliposomes group exposed efficient delivery systems of phytochemicals for the application in food and beverage products (Katouzian and Jafari, 2016). A solid dispersions of plant extracts into a phospholipid matrix will fabricate phytosomes, an appropriate delivery system for a low solubility and low bioavailability of bioactive compound. The structural characteristics is the resemblance of phytosomes and liposomes but nanophytosomes and nanoliposomes are distinctive in terms of stoichiometric ratio that bioactive compounds are chemically attached to the carrier structure which nanophytosomes may increase the storage and digestive stability through H bonds (Demirci et al., 2017). The drawback of liposome is bioactive compound that is not bound to the particle and this will trigger a leaking and so loss of encapsulated bioactives (Jafari, 2017). However, the phytosomes stabilization, the encapsulation efficiency (EE) enhancement and the bioactives stability are supported by the chemical bonding, specifically at a stoichiometric molar ratio (1:1 or 1:2) of phospholipids:phytochemicals. Phosphatidylcholine is a common phospholipid used in the operation of phytosomes. Moreover, pharmacokinetic and pharmacodynamic properties are highly better performed by phytosomes than liposomes and free plant extracts.

10.3.2  Nanolipid Carriers Recently, the attention toward nanolipid carriers that involve two groups; SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) are emerging because of their benefits compared to other nanoencapsulation technique with lipid-based such as nanoliposomes and nanoemulsions (Pyo et  al., 2017). The production of SLNs involved the emulsification of liquid mixture of hot lipid, which

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usually comprised of lecithin, mono-, di-, and tri-glycerides, free fatty acids, and nonionic surfactants by microfluidizer. However, SLNs have appropriate surfactants and formulations to produce a spontaneous emulsification with ultralow interfacial tension in a range of 50–900 nm. SLNs produced by the high- and low-energy method were then quickly cooled below the melting point of the lipid to turn them into glassy state. Thus, SLNs are allowed to load a various type of lipid soluble or lipid dispersible solutes. The fabrication of solid solutions is the major advantages of SLNs, which are possible in reducing the low soluble compounds and the tendency to form crystal at room temperature. The crystallization of lipid droplets with the inclusion of bioactive compound will then form nanoparticulate system called SLNs (Pandita et al., 2014). For example, SLNs is produced by incorporating resveratrol, stearic acid, and Poloxamer 188 through solvent diffusion-­ solvent evaporation method. As a result, lecithin concentration and homogenization rate was significantly affected the changing of particle size. In addition, there is an improvement at about eight fold on the oral bioavailability of resveratrol rather than its pure suspension when SLNs is fabricated with stearic acid and a mixture of surfactants (lecithin and Poloxamer 188). A development of SLNs is aimed to gain the advantages from other encapsulation techniques; namely polymeric particles, liposomes, and emulsions and also to overcome their disadvantages. SLNs could offer less complex of production and less challenging on their regulatory status of the applied excipients which are commonly natural and well accepted. Generally, the low ability to stabilize chemically labile bioactive ingredients and to improve controlled release is among the major problems of conventional emulsions and liposomes. However, NLCs are being applied in the nanoencapsulation process to overcome the weakness found in SLNs especially the low-loading capacity and the excretion of bioactive ingredients. The production of NLCs involved a dispersion of a mixture of solid and liquid lipids with the inclusion of bioactive compounds as internal phase into external aqueous phase composed of emulsifiers. A mixture of cocoa butter and hydrogenated palm oil are included in the preparation of SLNs and NLCs as the lipid phase by monitoring the thermal properties of the sample (Qian et al., 2013). The particle size of NLCs is controlled during storage; however, SLNs show an increase in mean particle size which then led to changes in morphology and/or aggregation of the particle. A lower degradation rate of β-carotene was observed due to color loss in NLCs than SLNs. This condition described the exclusion of β-carotene compound from the core of NPs during the crystallization of lipid phase, thus, this will contributed to a greater revelation of carotenoids to pro-oxidants in the aqueous phase matrix in the SLNs.

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The researchers concluded that SLNs exhibited a lower efficiency of encapsulation as well as β-carotene protection than NLCs. Thus, NLCs promoted a better entrapment ability of bioactive compounds due to more solubilized in the liquid lipid in the internal phase.

10.3.3 Nanogels Nanogels are formed by chemically or physically linked polymer network cross-linked hydrogel particles and the delivery system showed a great swelling ability in particular solvents (Buwalda et  al., 2017). Also, the term “hydrogel” is used when the solvent applied is water. Generally, the main purpose of nanogels is to deliver the drugs or bioactive compound which wholly or partly destabilize when responded to metabolic activities in human body or might be not penetrate through intestinal mucosal barrier. A nanogel could produce many benefits of the encapsulation process which are including the effectiveness in encapsulating bioactive compounds; the great protection against enzymatic outbreaks and aggregation caused by serum components; the stability of pH even when the breakages of nanogel and the prevention of any consequences of toxicity and abrupt release of bioactive compounds (Jafari, 2017). “Nonresponsive nanogels” happen when the swelling process of the delivery systems is merely absorbing water. The other subclasses of nanogel is “stimuli-­responsive” which the swelling and release properties of the nanogel systems are affected by environmental factors including pH, enzymes, ionic stresses, temperature, or magnetic fields (Sultana et al., 2013). In addition, the term multiresponsive nanogel defines as the responsiveness of a nanogel to more than one environmental stimulus. Nanohydrogels, a proposed delivery systems that can be operated to encapsulate functional compound, accumulate functional compound at the target cell, and decrease the effect of functional compound at the nontarget cell (Ahmadi et  al., 2015). The existence of hydrophilic moieties such as hydroxyl, carboxyl, ethers, amines, and sulfate groups will make nanohydrogels product to swell in water for about 30 times more than their initial size. Consequently, hydrophilic and amphiphilic polymer networks form a three-dimensional structure with the capacity to hold large amount of water and the presence of covalent and noncovalent interactions could maintain their structure which is soft and elastic. The occurrence of the interactions of electrostatic, van der Waal, hydrophobic within bioactive compounds and the matrix will aid in the manufacturing of nanohydrogels. Moreover, the stability of these nanostructures was heightened when formulating them using biopolymers, polysaccharides (alginate, chitosan, pectin, pullulan, and dextran), and proteins (whey proteins and collagen) and also various techniques.

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Moreover, technologies used that involve high temperature such as sonication and polymerization for the formation of nanogel structure may be caused unfavorable effect and this conditions must be well monitor during operation (Liu et al., 2017). This nanogel systems is said to be challenging and expensive due to the process of removing the solvents and surfactants on the final products which might cause a toxicity effects and thus the application of solvents and surfactants in the development of nanogels might contributed to the major drawbacks.

10.3.4 Nanoemulsion Bio-nanosystems such as nanoemulsion with different systems namely; oil-in-water (O/W), water-in-oil (W/O), and oil-in-oil (O/O) is an effective delivery system in terms of protecting bioactive phenolic compound as well as improving aqueous solubility, physical and chemical stability, bioavailability, and the performance of functional properties until it reaches the target sites. Typically, food industry used emulsion-based, the dispersion of liquid droplets into a liquid medium (Tadros, 2013) to produce beverages such as milk, ice cream, and soft drinks. For example, many investigations were done to develop the best formulation using nanoemulsion-based in order to enhance the functionality of bioactive phenolic compounds. Various nanoemulsion formulations have been applied using synthetic sources (Tween 20, Tween 80, Span 80, sugar ester, and glycerol monooleate, polyglycerol polyricinoleate) and natural sources (milk protein sodium caseinate, soy lecithin, pea protein, pectin, chitosan, whey protein isolate, WPI) of emulsifiers with different sources of oil phases (milk fat, sweet fennel oil, grape seed oil, orange oil, peanut oil, sunflower oil, diacetyl tartaric acid ester, and palm oil). There are some studies in the area of natural biopolymers and biopolymers complexes used as emulsifier in multiple emulsions that are possible in increasing the stability and EE of bioactive phenolic compounds. The resistance of the dispersed droplets to produce sedimentation or creaming in the continuous phase will identify the stability of an emulsion which will prevent the condition of coalescence and separation into two discrete phases. The absence of surfactant may lead to the separation of emulsions into the two phases. The surfactant functions as emulsifier, an amphiphilic organic compound that composed of hydrophilic (polar water soluble) and lipophilic (nonpolar oil soluble) portion. The head (water soluble) and tail (oil soluble) of emulsifiers are responsible in lowering the interfacial tension by adsorbing at the interface of the dispersed water droplets with the continuous oil phase. Several bioactive compounds such as tocopherol, alkylresorcinols, steryl ferulates, and other phenolic compounds were found abundantly

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in wheat bran oil (WBO). The low solubility in water systems had led to the manufacturing of nanoemulsions (O/W) of WBO (Rebolleda et al., 2015). The study conducted to obtain enhanced bioaccessibility of the WBO nanoemulsions by monitoring the influence of oil concentration, surfactant type and concentration, and emulsification method on their droplet size and stability. The optimal WBO nanoemulsions were achieved when 1% of WBO, 7.3% of a surfactant mixture (37.4% of Span 80 and 62.6% Tween 80) were homogenized using high-speed blender for 5 min and then using high-intensity ultrasonication for 5 s. The data were analyzed by response surface methodology (RSM) and the results showed a good stability and antioxidant as well as tyrosinase inhibitory activities. Consequently, WBO nanoemulsions might be used for a wide application in food industry. Moreover, Davidov-Pardo and McClements (2015) revealed a low-energy method is beneficial in preparing resveratrol-rich O/W emulsion in a range of 99–106 of nanometer (nm) size whereas 45–47 nm of size were obtained by high energy method. The delivery system used to encapsulate resveratrol was composed of oil phase (grape seed oil, GSO: orange oil, OO) with addition of synthetic surfactant (Tween 80) and titration of oil phase into aqueous phase. The addition of grape skin extract (GSE) had fewer impacts on the particle size for the nanoemulsion produced by high-energy approach than low-energy approach. However, oil phase had influenced the stability of the nanoemulsion. The optimum ratio of OO: GSO is 1:1 had shown good stability in terms of droplet growth. In another study by Sessa et al. (2014), various nanoemulsion-based delivery systems were formulated to improve bioavailability of resveratrol. Lecithin-based nanoemulsions were found to transport resveratrol through Caco-2 cells in the most effective way which is 1–6 h (shorter times) than 3–12 h of its metabolization time. Nanoemulsions of phenolic compounds from grape marc (0.1 %, w/w) were assisted by oil phase (sunflower oil and palm oil) with the combination of emulsifiers (hydrophilic and hydrophobic) and were formed using high pressure homogenization (Sessa et al., 2013).

10.4  Biopolymer- and Natural Lipid-Based Nanovehicle for Potential Functional Beverages The constitution of bio-based, biodegradable food-grade as an alternative to nonfood-grade materials for food applications are the most challenging part in nanotechnology (Cerqueira et  al., 2014). Surface active molecules such as polar lipids, protein, polysaccharide, and surfactants self-assemble are used to design delivery systems

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for nutraceuticals, vitamins, and minerals. The association colloids demonstrated the incorporation of safe food grade ingredients from one or more types of biopolymers like protein, polysaccharide, and polar lipids to produce ingenious formulation with improved texture properties and nutrients quality. An overview of ongoing research on the formulation of delivery nanosystem that proposed to be used in beverages industry is illustrated in Tables 10.1–10.4.

Table 10.1  Formulation of Delivery Nanosystem by Protein Assemblies Particle Size (nm)

Bioactive

Formulation

Technique

References

Polyphenols

Curcumin

Nanoemulsion (O/W)

40–250

Rao and Khanum (2016)

Polyphenols, terpenes, aldehydes

Carvacrol, limonene and cinnamaldehyde

Milk fat (oil phase) and milk protein sodium caseinate (wall material) Sunflower oil (oil phase), soy lecithin, sugar ester, pea protein, glycerol monooleate with tween 20

Nanoemulsion (O/W)

123–293

Donsì et al. (2012)

Table 10.2  Formulation of Delivery Nanosystem by Polysaccharide Assemblies Vitamin

Bioactive

Formulation

Technique

Particle Size (nm)

References

Tocotrienol

Emulsifiers (alginate-gum Arabic, Tweens, Brij 35:Span 80) Emulsifiers (κ-carrageenan and carboxymethylcellulose,CMC)

Nanoemulsion

<100 nm

Goh et al. (2015)

Nanohydrogel

Hezaveh and Muhamad (2012)

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Table 10.3  Formulation of Delivery Nanosystem by Protein-Polysaccharide Complex Perticle Size (nm)

Bioactive

Formulation

Technique

Polyphenols

Olive leaf extract

Nanoemulsion (W1/O/W2)

22–1992

Mohammadi et al. (2016a,b)

Polyphenols

Olive leaf extract

Nanoemulsion (W1/O/W2)

675–1443

Mohammadi et al. (2016a,b)

Polyphenols

Resveratrol

Nanoprecipitation

224–238

Davidov-Pardo et al. (2015)

Polyphenols

Picrocrocin, Saffranal, Crocin

Fatty acid

Linoleic acid, LA

Oil phase (Soybean oil, Span 80) Emulsifier (WPC, pectin) Oil phase (Soybean oil, Span 80) Emulsifier (WPC, pectin) Sodium caseinate, sodium caseinate-dextran, zeinsodium caseinate/sodium caseinate-dextran W1 (saffron extract), O (sunflower oil, Span 80), Single layer W2 (WPCMaltodextrin, WPC alone) or double layer W2 (WPCPectin simultaneously and sequentially) Emulsifier (Whey protein, Carrageenan)

Nanoemulsion

Nanoemulsion (O/W)

References

Esfanjani et al. (2015)

0.2–4 μm, 50–800 nm

Kouassi et al. (2012)

10.4.1  Protein Assemblies Recently, protein-based assemblies have been formulated to protect phenolic compound and lipid along the digestion system until they reach the specific sites. Whey protein concentrate (WPC) and whey protein isolate (WPI) have high protein compound at about 35%–80% and 90% that could be obtained from cheese whey or skim milk. (Svanborg et al., 2015). The WPC produced from skim milk exhibited unique functionalities including excellent solubility, gelling after heat treatment, and foaming properties (Heino et al., 2007). Whey proteins are suggested as an appropriate carrier in the formulation of nanodelivery vehicles for bioactive compound because it is resistant to some proteolytic enzymes (El-salam and El-shibiny, 2016). Whey protein treated with high-pressure microfluidization (HPM) at initially 40 MPa and raised up to 160 MPa has increased the percentage of solubility characteristic from 30 to 59 while foaming ability from 20 to 65

Table 10.4  Formulation of Delivery Nanosystem by Lipid Assemblies Bioactive Carotenoids

Polyphenols

Carotenoids

Polyphenols

Lutein, β-carotene, Lycopene, Canthaxanthin Resveratrol (grape skin extract, GSE) Lutein, β-carotene, Lycopene, Canthaxanthin Resveratrol

Polyphenols

Resveratrol (Grape marc)

Vitamin D

Elgocalciferol

Polyphenols

Resveratrol

Polyphenols

Curcumin

Formulation

Technique

Particle Size (nm)

Nanoliposome/ Chitosome

References Tan et al. (2016)

Nanoemulsion

Thin film evaporation method-carotenoids, chloroform, lipid (Egg yolk phosphatidylcholine, EYPC and Tween 80), sonication

Nanoliposome

Peanut oil-based with hydrophilic emulsifier (sugar ester, SE polysorbate Tween 20, and defatted soy lecithin, DSL) and lipophilic emulsifier (soy lecithin, LSL and glycerol monooleate) Sunflower oil and palm oil-based with hydrophilic emulsifier (defatted soy lecithin, DSL) and lipophilic emulsifier (soy lecithin, LSL and glycerol monooleate) Tripalmitin (triglyceride) and Tween 20

Nanoemulsion (O/W)

128–235

Sessa et al. (2014)

Nanoemulsion (O/W)

176–1330

Sessa et al. (2013)

Nanocarriers (Solid lipid nanoparticle, SLN) Nanoemulsion (O/W)

65–120

Patel and San Martin-Gonzalez (2012)

90–270

Sessa et al. (2011)

Nanoemulsion (O/W)

128–211

Donsì et al. (2011)

Peanut oil-based with hydrophilic emulsifier (sugar ester, SE polysorbate Tween 20, and defatted soy lecithin, DSL) and lipophilic emulsifier (soy lecithin, LSL and glycerol monooleate) Peanut oil-based for resveratrol, stearic acid and palm oilbased for curcumin with hydrophilic emulsifier (sugar ester, SE polysorbate Tween 20, and defatted soy lecithin, DSL) and lipophilic emulsifier (soy lecithin, LSL and glycerol monooleate)

Low-energy emulsion-99–220; high-energy emulsion-45–47

Davidov-Pardo and McClements (2015)

Grape seed oil:orange oil GSO:OO (oil phase)Tween 80

Tan et al. (2014)

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(Liu et al., 2011). However, HPM has modified the emulsifying capability of whey protein to become less efficient than untreated form. Caseins are also milk proteins that usually extracted from defatted milk through isoelectric precipitation at pH 4.6 with whey proteins contain in the residual liquid. A high degree of hydrophobicity of casein is associated with hydrophobic amino acids (Bhat et  al., 2016). A self-assembled micelles such as αs1-casein, αs2-casein, β-casein, and κ-casein intrinsically contain about 43%, 33%, 52%, and 43% of amino acids, respectively. Caseins are unique phosphoprotein with distinct hydrophobic and hydrophilic domains. They may form different sizes of self-assembled aggregates due to their amphipathic character which are hydrophobic and charged residues are unevenly disseminated along the polypeptide chain. β-casein could produce micelles in nanosize while the other caseins may form a larger or uncontrolled size. The combination of sodium caseinate and biopolymer is then incorporated in the encapsulation formulation to protect bioactive food ingredients in the core structure. There is a resemblance of milk proteins and anionic surfactant in terms of hydrophobic-anionic properties but milk proteins have no free monomers in solution. The supramolecular assemblies of proteins are triggered by pH changes through multivalent cations or complexation with polysaccharides (electrostatic forces or covalent bond) generated by Maillard reaction (Livney, 2010). Although hydrophobic core of milk proteins are possible in incorporating various hydrophobic solutes but the degradation of some digestive enzymes are the limitation. However, the triggered release is an advantage that could be gained from the limitation (Acosta, 2012). Table 10.1 shows Rao and Khanum (2016) implemented a solvent-­ free green chemistry process to encapsulate cucurmin in O/W nanoemulsion. A constant concentration ratio of oil phase (milk fat) to cucurmin is 1%–0.05%. The water phase containing wall material of sodium caseinate solution (milk protein) with varied concentrations is employed to examine the most stable formulation. As a result, 5% sodium caseinate is essential for the production of encapsulated cucurmin with 90.9% of EE, 0.9% of loading capacity, and 40 nm of particle size. Bioactive compounds such as carvacrol, limonene, and cinnamaldehyde were dispersed in sunflower oil and emulsified with four type of emulsifiers including lecithin, pea proteins, sugar ester, and the mixture of Tween 20 and glycerol monooleate using high-pressure homogenization (Donsì et  al., 2012). The formulations of nanoemulsion delivery system have affected the antimicrobial activity which might be related to the concentration of the essential oil constituents in the aqueous phase in equilibrium with the nanoemulsions droplets. This study suggested that nanoemulsions delivery system with emulsifiers of sugar esters and the mixture

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of glycerol monooleate and Tween 20 enhanced the ability of bioactive compounds to interact with cell membranes are related to their dissolution in the aqueous phase. Consequently, the antimicrobial compounds were immediately obtained and enhanced bactericidal activity was available in shorter time range (2 h). However, emulsifiers of lecithin and pea proteins exhibited the antimicrobial activity in a longer time range (24 h) because of less interaction between aqueous phase and bioactive compound.

10.4.2  Polysaccharide Assemblies The polysaccharides create emulsions that are less influenced by pH variations, high ionic strengths, and high temperatures rather than only proteins (Dickinson, 2003). For instance, Goh et  al. (2015) was found that the solution of 0.5% (weight/volume, w/v) alginate and 5% (w/v) gum Arabic and addition of 2.5% of emulsifiers (Tween series alone or mixture of Brij 35 and Span 80) through 10 cycles and 25,000 psi (172 MPa) of high pressure homogenization could improve solubility and absorption of tocotrienols with 65.1 nm of droplet size and a lower than 0.2 of polydispersity index (PDI). The study showed that solution of biopolymer complex from the blend of two natural polysaccharides, alginate, and gum Arabic could form a stable nanoemulsion with enhanced efficiency of delivery system. Table  10.2 shows the different formulations of delivery nanosystem by polysaccharide assemblies. The incorporation of metallic nanoparticles, NPs (silver, Ag, and magnetic) into a modified κ-carrageenan hydrogel matrix was done to form two nanocomposites hydrogel, and then the release behavior of methylene blue (MB) as a model drug in GIT was investigated (Hezaveh and Muhamad, 2012). As a result, nanocomposite hydrogel increases the MB release. In addition, Ag κ-carrageenan nanocomposite exhibited a better effect on release properties of MB when cross-linked by genipin compared to magnetic NPs. Thus, a potential GIT controlled drug delivery might be developed by loading metallic NPs.

10.5  Protein-Polysaccharide Complex The adsorption of protein and polysaccharide mixture will rely on the concentration and surface activity of adsorbed biopolymer type as well as the nature and strength of the interaction between protein and polysaccharide (Liu et al., 2017). The way that the two biopolymers presented to the interface by either sequence or simultaneous will affect the mixture of protein-polysaccharide in terms of the structure and the colloidal stabilizing properties. Table  10.3

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shows different formulations of delivery nanosystem by protein-­ polysaccharide complex. Several studies showed a larger droplet size when using low-­ energy method. Firstly, layer-by-layer of protein-polysaccharide was promoted O/W emulsion stability and 83% of EE of linoleic acid with 0.2–4 μm of average lateral size range, however, the height of capsules achieved nanometer size within 50 and 800 nm (Kouassi et al., 2012). Whey protein and κ-carrageenan (polysaccharide) are a natural biopolymer that provides a protective layer in the encapsulation of linoleic acid. Moreover, Mohammadi et al. (2016) investigated an antioxidant activity of olive leaf extract encapsulated by W/O/W emulsions. The system incorporated of olive leaf extract from microwave-assisted extraction as a bioactive phenolic compound, soybean oil as an oil phase, and whey protein concentrate, WPC alone or WPC-Pectin as biopolymer of protein-polysaccharide offered W/O/W nanoemulsion with improved solubility, antioxidant activity, and controlled release. Consequently, a solution of protein-polysaccharide complex (WPC-Pectin) produced 1443 nm of W/O/W emulsion whereas WPC formed 675 nm of emulsion particle size. Mohammadi et al. (2016) formulated the similar delivery system as Mohammadi et al. (2016) but evaluated the storage stability of nanoemulsions for 20 days and found that W/O emulsion, W/O/W emulsion with WPC and WPC-Pectin obtained 22.97, 347.7, and 1992.4 nm of particle size, respectively. In addition, WPC-Pectin-loaded W/O/W emulsion showed the slower release rate rather than WPC only. Saffron extract (crocin, picrocrocin, and safranal) was encapsulated in W/O/W multiple emulsions (Esfanjani et al., 2015). Layer by layer (sequential) adsorption of WPCpectin exhibited higher encapsulation stability than the solution of WPC-pectin (simultaneously). Davidov-Pardo et  al. (2015) fabricated resveratrol-loaded coreshell NPs (zein + antisolvent phase) and biopolymer complexes (sodium caseinate or maillard conjugated). Antisolvent phase comprises sodium caseinate solution or maillard conjugate of sodium caseinate and dextran. They investigated the bioaccessibility of resveratrol in two delivery nanosystems; biopolymer NPs and biopolymer complexes. As a result, biopolymer NPs (83%) showed higher resveratrol retention efficiency than the biopolymer complexes (68%). This study revealed that protein-polysaccharide complex (zein + antisolvent phase) provide a better protection of bioactive compound against environmental stresses than only polysaccharide-­ polysaccharide complex (sodium caseinate solution or sodium ­caseinate + dextran). The authors also concluded that dextran had less influence on the particle size of the delivery nanosystem and hydrophobic forces are known to play an important role in the binding of polyphenols to protein.

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10.6  Lipids Assemblies SLNs are one of a technique that had been used as a nanovehicle for a potential functional compound. Table  10.4 shows the different formulations of delivery nanosystem by lipid assemblies. Chitosomes was performed by the preparation of liposomes and layer self-­assembly deposition technique in order to encapsulate four types of carotenoids, including lycopene, β-carotene, lutein, and canthaxanthin (Tan et al., 2016). In this study, several analyses such as microstructure, particle size, and distribution using transmission electron microscopy (TEM) and dynamic light scattering were done to characterize the colloidal nanocarriers. The electrostatic attraction was responsible for the chitosan adsorption onto membrane surface, by inducing charge inversion without changing the spherical shape of liposomes. The interaction of chitosan with liposomal membrane had been discovered through fluorescence polarization analysis, which exposing that electrostatic and hydrophobic interaction controlled the motion freedom of lipid molecules and improved their positioning at the polar headgroup section and hydrophobic core of the membrane. Consequently, these interactions explained the rigidifying effects that directly contributed to the stabilization of carotenoid-loaded liposomes and prevention overheating, GI stress, and centrifugal sedimentation. Chitosomes potent to encapsulate carotenoids of different structures, however, it was highly depended on their molecular structure as there is a higher EE in shielding β-carotene and lutein compared to lycopene and canthaxanthin by the thin biopolymer-coated layer. Thus, Tan et al. (2016) suggested that chitosomes may serve as a delivery system for bioactive compounds. Moreover, Davidov-Pardo and McClements (2015) revealed a low-energy method is beneficial in preparing resveratrol-rich O/W emulsion in a range of 99–106 of nanometer (nm) size whereas 45–47 nm of size were obtained by high energy method. The delivery system used to encapsulate resveratrol was composed of oil phase (grape seed oil, GSO: orange oil, OO) with the addition of surfactant (Tween 80) and titration of oil phase into aqueous phase. The addition of GSE had fewer impacts on the particle size for the nanoemulsion produced by high-energy approach than low-energy approach. However, oil phase had influenced the stability of the nanoemulsion. The optimum ratio of OO: GSO is 1:1 had shown good stability in terms of droplet growth. In another study by Sessa et al. (2014), various nanoemulsion-­based delivery systems were formulated to improve bioavailability of resveratrol. Lecithin-based nanoemulsions are found to transport resveratrol through Caco-2 cells in the most effective way which is 1–6 h (shorter times) compared with 3–12 h of its metabolization time. Nanoemulsions of phenolic compounds from

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grape marc (0.1%, w/w) were assisted by oil phase (sunflower oil and palm oil) with the combination of emulsifiers (hydrophilic and hydrophobic) and were formed using high-pressure homogenization (Sessa et al., 2013). Tan et al. (2014) revealed that the efficiency of antioxidant retention on carotenoids components by liposome encapsulation. Lutein showed the strongest antioxidant capacity, followed by β-carotene, lycopene, and canthaxanthin when measured by DPPH, FRAP, and lipid peroxidation inhibition capacity (LPIC). The antioxidant activity of carotenoids in liposome system comprised of egg yolk phosphatidylcholine (EYPC) and Tween 80 as lipids was associated with their chemical reactivity and EE and also modulating the effects of liposomal membranes. A melt-homogenization technique using a nozzle-type high pressure had been applied in the formation of ergocalciferol (vitamin D) loaded tripalmitin SLNs, SLNs with Tween 20 as a stabilizer (Patel and San Martin-Gonzalez, 2012). There is a decrease of Z-average values of the particles from 120 nm to about 65 nm when the concentration of ergocalciferol in the nanocarrier is raised from 0% to 20%. A gradual decrease in enthalpies of fusion and crystallization was observed for stable β-subcell of freeze dried SLN by DSC analysis whereas SLN dispersions showed an increase of the enthalpy of fusion of unstable α-subcell crystal when the proportion of ergocalciferol is loading. The ergocalciferol-loaded SLN was proved to show the spherical and rodshaped NPs by microstructure analysis using TEM. The system had exposed a decreasing in the particle size of the NPs linearly, which might lead to the decreasing of SLN dispersions turbidity. Thus, the finding resulted a promising application in fortificating the ergocalciferol into clear and cloudy juices. EE was heightened and also the stability of the encapsulated compound had enhanced which was contributed by the changes in enthalpy values of SLN from the different polymorphs with increased ergocalciferol. Several investigation had been done by Sessa et  al. (2011) on physicochemical stability of encapsulated resveratrol by O/W nanoemulsions under accelerated aging (high temperature and UV light exposure) and simulated GI digestion. The nanoemulsion formulated using high-pressure homogenization with soy lecithin/sugar esters and Tween 20/glycerol monooleate were revealed to have the highest physical and chemical stability when referring to less than 180 nm of particle size and resveratrol loading during both condition; accelerated aging and GI digestion. In addition, Sessa et al. (2011) suggested that nanoencapsulated resveratrol not metabolized in the GIT but might be absorbed through the intestinal wall in active form, because of the highest chemical and cellular antioxidant activities of both formulations compared to unencapsulated resveratrol in DMSO solution. After

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gastric and intestinal digestion, the nanoemulsion delivery systems are stable and the antioxidant compounds in active form are readily to be absorbed by the cells when observing that the cellular antioxidant activity of encapsulated resveratrol had not significantly affected by digestion process. Consequently, this study recommended that the nanoemulsion formulation could be an appropriate model for developing delivery systems of nutraceutical and functional food ingredients with enhanced efficiency, stability, and bioavailability. The encapsulation of bioactive compounds using nanoemulsion delivery systems are an intelligent approach in improving the dispersion of the bioactives into food products, protecting them against degradation or interaction with other ingredients, reducing the impact on organoleptic properties of food and beverage, and improving their bioavailability (Donsì et al., 2011). For example, curcumin and resveratrol are incorporated in nanoemulsions with the purpose to enhance their antioxidant and/or antimicrobial activities. The high pressure homogenization had been applied to achieve the nanosize in less than 200. For nanoemulsion of resveratrol (0.1% wt), peanut oil is used as oil phase as well as soy lecithin and sugar esters as emulsifiers. However, curcumin was fabricated with stearic acid as lipid phase.

10.7  Bioactive Compound/Functional Properties of Nano-Ingredient in Beverages There are various types of supplement in beverages form that are available in the market for various functions mainly for human health. Table 10.5 shows the summary of product information including the manufacturing company, the commercial name of the products and the formulation or technology involved in the production. However, only some of the products show the encapsulation information such as the wall material and the specific application on health in the product description. The inorganic or nonbiodegradable materials such as nanoSilver, nanoTitanium, nanoZinc, nanoSilica might cause harmful effects (Martirosyan and Schneider, 2014). For example, NPs such as nanoSilver (Ag NPs) was reported to cause toxicity to mammalian cells and human health and damage to brain, liver, and GIT cells. NanoTitanium (TiO2 NPs) is an effective carrier used in medicines, pharmaceuticals, nutritional supplements, and food products, however, the carrier may promote localized effect by the translocation into systemic circulation from lung or GIT and then disseminated in certain organs including livers, kidneys, spleen, or brain. NanoZinc (ZnO NPs) is similar to TiO2 NPs and might also cause damage to lung, liver, and kidney. SiO2 (Silica) NPs usually applied as anticaking agent, could easily be absorbed from human intestine and no conclusion on its bioavailability can be made so far.

Table 10.5  Nano-Engineered Products in the Market No

Company

Product

Formulation/Technology

1

Qinhuangdao Taiji Ring Nano-Products Company Ltd, China

Nano-Selenium Rich Green Tea

2

Solgar, Inc

Nutri-Nano CoQ-10 3.1 × Softgels

3

Purest Colloids, Inc.

Microhydrin

4

Nu Skin

LifePak Nano

5

RBC Life Sciences, Inc.

Silver-22TM

6

RBC Life Sciences, Inc.

HydracelTM

7

Genceutic Naturals

24Hr Microactive CoQ10

8

Vitality Products Co., Inc

ACZ Nano Advanced Cellular Zeolite

9

American Biotech Labs

ASAP Health Max 30

Nanoparticles: (i) Selenium Functions of Nanomaterial: (i) Wide-spectrum antibacteria and antivirus Emulsifier: Polysorbate 80 Softgel Capsule Shell: Gelatin (from bovine), vegetable glycerin (from palm kernel oil and coconut oil) Nanoparticles: (i) Silicon Functions of Nanomaterial: (i) Health applications Nanoparticles: (i) Copper (ii) Silicon (iii) Zinc oxide Functions of Nanomaterial: (i) Hardness and strength (ii) Health applications Nanoparticles: (i) Silver Functions of Nanomaterial: (i) Health applications (ii) Antimicrobial protection Nanomaterials: (i) Mineral clusters Functions of Nanomaterial: (i) Improves alkalinity in drinking water (ii) Lowers surface tension of water for improved hydration Nanomaterials: (i) Calcium (ii) Magnesium Functions of Nanomaterial: (i) Health applications Nanomaterials: (i) Zeolite Functions of Nanomaterial: (i) Health applications Nanomaterials: (i) Silver Functions of Nanomaterial: (i) Antimicrobial protection

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The uses of biopolymer NPs in nanoencapsulation of bioactive compounds, especially phenolic compound and antioxidant have been discussed in terms of their formulation, production, and characterization (Faridi Esfanjani and Jafari, 2016). Consequently, recent studies on the application of biopolymer NPs; protein assemblies, polysaccharide assemblies, and protein-polysaccharide complex as well as natural lipid for the encapsulation of bioactive compounds had been discussed in Section  10.3. The nanovehicles are designed and formulated to serve their uses as potential ingredients in functional beverages. Polyphenol (resveratrol, curcumin, picrocrocin, safranal, crocin, carvacrol, and olive leaf extract), vitamins (D and E), essential fatty acids (linoleic acid), carotenoids (lutein, carotene, lycopene, and canthaxanthin), terpenes (limonene), and aldehydes (cinnamaldehyde) are the bioactive compounds that have been incorporated into nanoencapsulation formulation through several method such as nanoemulsions, nanogels, nanoliposomes, and nanolipid carriers which were being investigated on their suitability to be used as efficient delivery systems/nanovehicle in beverages product.

10.8  Nanocapsules as Delivery Systems in the Beverage Industry 10.8.1  Characterization of the Nanocapsules 10.8.1.1  Particle Size Size and size distribution are the major factors that influence the stability, functional properties, and release of nanoencapsulation. The dissolution rate becomes greater as the particle size becomes smaller. The increase of particle specific surface area influences the reduction of thickness of the diffusion layer around each particle (Recharla et al., 2017). In order to enrich the beverages, the formulation of nanoencapsulation below 100 nm needs to be optimized. The information about the size such as particle size distribution, PDI, and zeta potential of the distribution can be identified by several tests (Jafari, 2017).

10.8.1.2 Morphology The word “morphology” is originated from Greek in which morph- means “shape, form,” and morphology is the study of form or structures of organisms (Aronoff and Fudeman, 2005). Morphology demonstrates the shape, size, uniformity, and the intactness of the encapsulated substances. Nanoencapsulation is greatly affected by the morphology for its functional properties, physicochemical condition, and stability. Important information on the structure and shape can

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be acquired by using microscopic studies to prepare and interpret the images (Jafari, 2017). Electron microscopy is usually used in the research which includes TEM and scanning electron microscopy (SEM). Scattering techniques with the light source of laser light, X-rays, or neutrons can be used to analyze the particle dimension and size distribution (Jafari, 2017). According to the study by Zhao et  al. (2017), the morphology of single liposomes was evaluated using a conventional TEM technique. The morphology is important to manipulate liposome properties in drug and nutraceutical delivery applications. Small and spherical liposome with a uniform size distribution and without any roughness or rupture on the surface is ideal. Diverse TEM images ranging from spherical to near-squared vesicles prepared by the SC-CO2 method were shown. Irregularity in the membrane and leakage in the vesicles of liposomes was revealed at lower pressure (60–100 bar) while enhanced spherical shape and intactness was displayed at high pressure. Meanwhile, higher temperature ranging from 50°C to 65°C yielded liposomes with more uniform packing and spherical shape, which may be attributed to the improved fluidity of membranes derived with an elevated energy input. The increasing ratio of lutein-to-lipid showed an improvement in the spherical shape and remained spherical (at ≤10%) but transformed into near-squared at the ratio of 20%. Overall, 300 bar, 120 bar/min, 5% lutein, and 65°C were found to give the recommended morphology. Based on the report by Vanitha et al. (2017), the morphology of silver NPs with different concentrations of AgNO3 (0.01, 0.1, 0.5 M) is spherical with nonuniformity in size distribution. The silver NPs with uniform size distribution were achieved with 0.1 M concentration of AgNO3. The particle size using TEM analysis showed an increment with an increase in AgNO3 concentration from 0.01 to 0.1 M and later decreased. This is due to the interaction effect of production of silver ions and influence of stabilizer (trisodium citrate). In the research of peppermint encapsulation with gelatin/gum Arabic by complex coacervation by Dong et al. (2011), the morphology of dried coacervate microcapsules was observed by Quanta-200 scanning electron microscope (SEM; FEI Corporation, Netherlands). The effect of core/wall ratio on the loading (oil content) and particle size of coacervate microcapsules was very significant. The release rate of the encapsulated peppermint was improved with the high loading which also decreased the thickness of microcapsules membrane. However, bigger particle size increased diffusing distance of peppermint oil which decreases release rate of coacervate microcapsules in the later phase of release. The release of coacervate microcapsules in cold water was very slow, and the effect of core/wall weight ratio on the release of coacervate microcapsules was not obvious. The coacervate microcapsules possessed excellent storage stability in cold water.

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10.8.1.3  Thermal Stability Temperature has important impact on the physical properties including CO2 solubility, density, and volumetric expansion. Is also affects the bilayer membranes properties such as degree of order, fluidity, permeability, and solubility (Zhao et al., 2017). The temperature rise commonly increases the solubility for most of the solid and liquid. This is because the solvent molecules are breaking apart the solute molecules more effectively as the kinetic energy escalates with temperature (Recharla et  al., 2017). In order to study about the thermal stability, the effect of temperature on the particle size (mean diameter), size distribution (polydispersity index, PDI), EE, and bioactive loading (BL) of liposomes were investigated throughout the experiment (Zhao et al., 2017). Zhao et al. (2017) reported that although higher EE was achieved by using temperature of 65°C, 50°C was selected because the lutein will undergo thermal degradation if the processing temperature was ≥60°C. This shows that thermal degradation is important to formulate the encapsulation with optimum stability. In the recent research by Pu and Tang (2017), the thermal stability of lycopene loaded in Chlorella pyrenoidosa cell (CPC) was examined by using thermogravimetric analysis (TGA), and differential scanning calorimetric (DSC) analysis. TGA analysis showed that 83.02% of unloaded lycopene degraded at 600°C while CPC-loaded lycopene degraded by 78.26% in the same condition, resulting in 21.73% residual matter in CPC-loaded compared to 16.98% in unloaded lycopene. The CPC-loaded lycopene proved that it is more stable compared to the unloaded lycopene with significant difference in the degradation. DSC analysis can be used to determine the physiochemical feature of active substances in numerous complexes, mainly to detect changes in the crystal lattice, melting, and boiling points through the shift or elimination of the endothermic peaks. The elimination of the characteristic endothermic peak of Algae at 229.26°C and the shift of the water elimination peak from 125.14°C to 150.45°C suggested that lycopene and CPCs had formed a homogenous system (Pu and Tang, 2017).

10.8.1.4 Photostability Ultraviolet (UV) radiation may cause degradation to various materials. The degradation is caused by exposure of UV, which deteriorates the mechanical properties by reducing molecular weight through the production of free radical substance and polymer chains breakage. Photodegradation is the degradation of photodegradable molecule by the photon absorption of infrared radiation, visible light, and UV light. The photons break up the molecules into smaller pieces to make it irreversibly altered by denaturing the proteins and addition of other

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atoms or molecules (Yousif and Haddad, 2013). According to the study by Kfoury et al. (2016), the photodegradation of phenylpropenes was reduced significantly by the encapsulation with cyclodextrins (CDs). The stability of trans-anethole, estragole, eugenol, and isoeugenol was notably higher by 18–44, 6–18, 1.5–2, and 1.6- to threefold, respectively. This indicated that encapsulation in CDs for phenylpropenes could be proper way for storage in a solid state as well as providing photoprotective effect. Cyclodextrin inclusion complexes (CD-ICs) encapsulated into electrospun nanofibers was studied by Aytac and Uyar (2016). CD-ICs reduced the photolytic reaction because it creates more apolar environment. The nanofibers sustained their fibrous structure to prevent the UV light from deteriorating the fibrous morphology.

10.9  Release Properties of Nanoparticle in Beverages Major challenges including poor aqueous solubility, sensory characteristics, instability of chemical in bioactive compounds, and antioxidant activity during processing should be considered in incorporating bioactive compounds into foods. Solubility is one of the core requirements to incorporate bioactive compounds in beverages and foods. There are a lot of techniques available to enhance the solubility of lipophilic bioactive compounds. Physical and chemical properties of bioactive compound and delivery system mode should help to determine the selection of suitable solubility (Recharla et al., 2017). The crocin nanoencapsulation release data were assessed kinetically using zero-order, first-order, Higuchi, and Ritger-Peppas models. The release profile of crocin-loaded with Angum gum (AG) shows that the release of core material (bioactive) can be controlled by using a proper hydrocolloid biopolymer without adjusting osmotic pressure between inner and outer phases. Although AG stabilized emulsions produced the highest droplet size, they contain lowest creaming and highest stability which could be credited to its high viscosity (Mehrnia et al., 2017). Wang et al. (2017) studied the ginkgo biloba extracts (GBEs)-loaded starch-nano-spheres (SNPs) release. The shell of the GBE-SNPs gradually thinned, and the black entities (GBEs) in the TEM images were steadily separated and diffused from the internal to the external surface with the increase of digestion time, indicating that the GBEs were progressively diffused out from SNPs. It shows the increase of the bioavailability, and that the delivery system improved the drug absorption in the GIT by active endocytosis.

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10.10  Bioavailability in GI Digestion (In Vitro, In Vivo) The dissolution in the GI tract, postprandial changes in GI physiology, and specific interactions between drug and food is the rate-­ determining step to the intestinal absorption of poorly soluble drugs. These interactions are expected to affect the pharmacokinetics and bioavailability of such drugs (Shono et al., 2009). Drug dissolution is required for drug absorption which influences the rate and the distance the administered dose of a drug can reach in the general circulation. The time for the drug to release its content and dissolve will affect the drug dissolution. The affinity between the solid and the surrounding liquid medium controls the dissolving process. The aqueous solubility, crystalline form, drug lipophilicity, and pKa of a drug related to the GI pH profile determine the solubility in the GI fluid contents (Jambhekar and Breen, 2013). In vivo dissolution of the drug depends on the physicochemical characteristics of the nanocapsules (i.e., particle size, molecular size and stability) and physiological condition (i.e., motility, available fluid volume, fluid viscosity, and food components). All these factors influencing drug dissolution will probably influence drug absorption and bioavailability. In vitro dissolution experiments are done by simulating the before and after condition of the small intestine such as fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF). It has been proven as a convenient tool to predict in vivo performance of drug products (Shono et al., 2009). In the study by Arunkumar et al. (2013), the biological availability of lutein with low-molecular-weight chitosan (LMWC) is expected to be much better compared to the purified lutein as control. The bioavailability of LMWC nanoencapsules loaded with hydrophobic lutein was studied in vitro using simulated digestion model (Garrett, et al., 1999) and in  vivo by using mice model. The percent of micellarable lutein in vitro was higher (27.7%) in LMWC NPs than control while the results from mice studies showed that the lutein content in plasma (54.5%), liver (53.9%), and eyes (62.8%) were higher than the control group after a single oral dose of lutein nanoencapsules. Resveratrol was encapsulated in soy lecithin/sugar esters and Tween 20/glycerol monooleate using high-pressure homogenization by Sessa et al. (2011), and the results showed that the nanoemulsions were the most physically and chemically stable exhibiting the highest chemical and cellular antioxidant activities, which was comparable to unencapsulated resveratrol dissolved in dimethyl sulfoxide (DMSO), suggesting that nanoencapsulated resveratrol, not being metabolized in the GIT, can be potentially absorbed through the intestinal wall in active form. Nanoencapsulation of green tea catechins by electrospraying technique was investigated to employ

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zein which is known as a biocompatible, biodegradable macromolecule by using various zein concentrations, and ratio of core-to-wall material. The combination of pepsin-mediated erosion during the gastric digestion and diffusion mechanism helps the catechins release from the wall matrix. In vitro GI stability and Caco-2 cell monolayer permeability has greatly improved with nanoencapsulation (Bhushani et al., 2017). In vitro toxicity of silver NPs to mammalian cells was studied by using mouse spermatogonial stem cells (C18-4) resulting reduced mitochondrial function, increased lactase dehydrogenase (LDH) leakage, and apoptosis.

10.11  Positive Impacts of Beverages With Nano-Ingredient on Human Health Nano-engineered foods are invented in order to improve the quality, safety, nutritional value, and reduce costs. It raised the expectations of the researchers, food manufacturers, and consumers concerning the possibility of enhancing the quality and functionality of the bioactive compounds in the food (Aditya et al., 2017). The food can be formulated according to the demands such as individual dietary, health requirements, or taste preferences, which can benefit the consumers as well as the industries with new market opportunities and economic advances (Handford et  al., 2014). One of the important factors that influence the nanotechnology foods acceptance is the naturalness of the food. Consumers have better acceptance for GM products that are recognized as more natural compared to the less natural. Thus, the naturalness of the foods with tolerable perceived risks and abundant perceived benefits would influence the public acceptance (Siegrist et al., 2008). Extensive research and patents has been performed about the encapsulation approach on the quality of food and beverage products, as well as their release and digestibility has been studied in  vivo and in  vitro. Nonetheless, the findings on their bioavailability and application in food matrices are insufficient (Dias et  al., 2017). Nano-delivery systems propose opportunities related to prolonged GI retention time by reducing the size of encapsulates into the nanoscale. The bioactive compound may be shielded from degradation, and improved stability and solubility might achieved delivery to cells and tissues (Bouwmeester et al., 2009). There are a lot of researches that have been done previously on the release behavior of the NPs but there is little exposure on its effect directly on human health. However, the level of toxicity will correspondingly increase in case of toxic material as the particles in in nano size. This is because the food absorption and the metabolics activity increases as the particle size decreases. As for the digestion and absorption rate of the

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c­ omponent materials may vary in different biological system and has the probability of creating potential health problems (Echiegu, 2017). The mentioned potential problems above show the need for regulations as a guide to use nanomaterials for nanotechnology in the food industry. There are a lot of regulatory bodies that controls and monitors the food production such as European Food and Safety Authority (EFSA), the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) of the USA, and the National Institute for Occupational Safety and Health (NIOSH) but specific regulation for nanotechnology guideline should be implemented and conducted by these bodies (Echiegu, 2017). In order to establish rules and regulation for nanotechnology, Bouwmeester et al. (2009) reported that there are numbers of aspect that should be taken into the account. For example, a risk assessment establishment for NPs to assist the regulatory discussions, research prioritization, and research exchange. Next, analytical tools for characterization of NPs and its discovery in the food matrices should be developed to estimate the exposure, kinetics, and toxicology for specific dose and the response. The kinetics of oral bioavailability and toxicity in specific body parts should be investigated. The commercial NPs or those which are being developed should be assessed by their types and consumption. A detailed regulatory approach for the NPs production and association information disclosure should be designed.

10.12  Safety Issues and Challenges of Beverages With Nano-Ingredient Nanotechnology has gained interest in food industry in recent years with the increasing application of engineered nano particles (ENPs) in various productions of appliances and consumer items (Goswami et al., 2017). Nanotechnology applications are expected to bring huge benefits to the food industry by introducing broad range of new taste, texture, healthier, advanced absorption of nutrients, enhanced packaging, and security of the food products (Chaudhry et al., 2008). However, there are suspicions among the consumers on the food products and packaging materials that use nanomaterials whether they are safe to be consumed or will not affect human body negatively (Jafari, 2017). Potential benefits of new evolving technologies are emphasized but the safety information of the nanotechnologies in food sector is hardly known (Bouwmeester et  al., 2009). ENPs have the potential to exhibit different properties from their nonnano counterparts as a result of ­surface-to-mass ratio increment and higher surface reactivity and able to penetrate biological barriers and cause contrary biological responses and health outcomes (Eleftheriadou et al., 2017).

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There are numerous safety issues and challenges that arise with the application of nanotechnology in food and beverages. For example, the release system of the NPs is not guaranteed to be in the targeted body parts as it can be transported through the bloodstream to other vital organs which may lead to cardiovascular or extrapulmonary complications. Also, the high reactivity and mobility of NPs might generate bioaccumulation and toxicity to human health and environment. The challenges of nanotechnology existed because there is little firm and persistent knowledge on the exposure evaluation and the toxicity; nonetheless the knowledge of the toxicology of nanomaterials is continuously progressing (Di Sia, 2017). The ENPs information on the benefits, food safety, quality, and nutrient improvement should be well documented in order to expand the commercialization. The understanding of potential risks of ENPs to humans, animal, and environment should complement the new materials development (Eleftheriadou et  al., 2017). Therefore, the risk assessment containing analytical approaches to provide decision makers with guidelines on how to formulate NP design with balanced risk and technological profits and costs should be implemented (Fadel et al., 2015). Validated and reliable science-based methods and tools were assessed by US regulatory community and nanotechnology industry to enhance current approach for risk analysis and regulation of NPs. The efforts include collecting the environmental, health, and safety (EHS) risk information to identify the nanomaterials procedures and effects. National Nanotechnology Initiative (NNI) has organized workshops to deliver and discuss the relevant policy on the application of the information retrieved (Fadel et  al., 2015). A successful implementation of the regulation and guidelines of nanotechnology will produce advanced environmental sustainability and global economic growth (Eleftheriadou et al., 2017).

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