Encapsulation of polyphenols – a review

Trends in Food Science & Technology 21 (2010) 510e523

Review

Encapsulation of polyphenols e a review Zhongxiang Fanga,b,* and Bhesh Bhandaria a

School of Land, Crop and Food Sciences, The University of Queensland, Brisbane, Qld 4072, Australia b School of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310029, China (School of Land, Crop and Food Sciences, The University of Queensland, Brisbane, Qld 4072, Australia. Tel.: D61 7 33469187; e-mail: [email protected]) Research on and the application of polyphenols, have recently attracted great interest in the functional foods, nutraceutical and pharmaceutical industries, due to their potential health benefits to humans. However, the effectiveness of polyphenols depends on preserving the stability, bioactivity and bioavailability of the active ingredients. The unpleasant taste of most phenolic compounds also limits their application. The utilization of encapsulated polyphenols, instead of free compounds, can effectively alleviate these deficiencies. The technologies of encapsulation of polyphenols, including spray drying, coacervation, liposome entrapment, inclusion complexation, cocrystallization, nanoencapsulation, freeze drying, yeast encapsulation and emulsion, are discussed in this review. Current research, developments and trends are also discussed.

Introduction Microencapsulation, developed approximately 60 years ago, is defined as a technology of packaging solids, liquids, or gaseous materials in miniature, sealed capsules that can release their contents at controlled rates under specific conditions (Desai & Park, 2005; Vilstrup, 2001). The packaged materials can be pure materials or a mixture, which are also called coated material, core material, actives, fill, internal * Corresponding author. 0924-2244/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tifs.2010.08.003

phase or payload. On the other hand, the packaging materials are called coating material, wall material, capsule, membrane, carrier or shell, which can be made of sugars, gums, proteins, natural and modified polysaccharides, lipids and synthetic polymers (Gibbs, Kermasha, Alli, & Mulligan, 1999; Mozafari, 2006) Microcapsules are small vesicles or particulates that may range from sub-micron to several millimeters in size (Dziezak, 1998). Many morphologies can be produced for encapsulation, but two major morphologies are more commonly seen (Fig. 1): one is mononuclear capsules, which have a single core enveloped by a shell, while the other is aggregates, which have many cores embedded in a matrix (Schrooyen, van der Meer, & De Kruif, 2001). Their specific shapes in different systems are influenced by the process technologies, and by the core and wall materials from which the capsules are made. Various techniques are used for encapsulation. In general, three steps are involved in the encapsulation of bioactive agents: (i) the formation of the wall around the material to be encapsulated; (ii) ensuring that undesired leakage does not occur; (iii) ensuring that undesired materials are kept out (Gibbs et al., 1999; Mozafari et al., 2008). The current encapsulation techniques include spray drying, spray cooling/chilling, extrusion, fluidized bed coating, coacervation, liposome entrapment, inclusion complexation, centrifugal suspension separation, lyophilization, cocrystallization and emulsion, etc. (Augustin & Hemar, 2009; Desai & Park, 2005; Gibbs et al., 1999). The main objective of encapsulation is to protect the core material from adverse environmental conditions, such as undesirable effects of light, moisture, and oxygen, thereby contributing to an increase in the shelf life of the product, and promoting a controlled liberation of the encapsulate (Shahidi & Han, 1993). In the food industry, the microencapsulation process can be applied for a variety of reasons, which have been summarized by Desai and Park (2005) as follows: (i) protection of the core material from degradation by reducing its reactivity to its outside environment; (ii) reduction of the evaporation or transfer rate of the core material to the outside environment; (iii) modification of the physical characteristics of the original material to allow easier handling; (iv) tailoring the release of the core material slowly over time, or at a particular time; (v) to mask an unwanted flavor or taste of the core material; (vi) dilution of the core material when only small amounts are

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Wall material

Wall material

Core material

Core material

Fig. 1. Two major forms of encapsulation: mononuclear capsule (left) and aggregate (right).

required, while achieving uniform dispersion in the host material; (vii) to help separate the components of the mixture that would otherwise react with one another. Food ingredients of acidulants, flavoring agents, sweeteners, colorants, lipids, vitamins and minerals, enzymes and microorganisms, are encapsulated using different technologies (Desai & Park, 2005). Recently, research and application of polyphenols have been areas of great interest in the functional foods, nutraceutical and pharmaceutical industries (Manach, Scalbert, Morand, Re´me´sy, & Jime´nez, 2004; Scalbert, Manach, Morand, Re´me´sy, & Jime´nez, 2005). Polyphenols constitute one of the most numerous and ubiquitous groups of plant metabolites, and are an integral part of both human and animal diets which possess a high spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, and antiviral functions (Bennick, 2002; Haslam, 1996; Quideau & Feldman, 1996). A large body of preclinical research and epidemiological data suggests that plant polyphenols can slow the progression of certain cancers, reduce the risks of cardiovascular disease, neurodegenerative diseases, diabetes, or osteoporosis, suggesting that plant polyphenols might act as potential chemopreventive and anti-cancer agents in humans (Arts & Hollman, 2005; Scalbert, Johnson, & Saltmarsh, 2005; Scalbert, Manach et al., 2005; Surh, 2003). Unfortunately, the concentrations of polyphenols that appear effective in vitro are often of an order of magnitude higher than the levels measured in vivo. The effectiveness of nutraceutical products in preventing diseases depends on preserving the bioavailability of the active ingredients (Bell, 2001). This is a big challenge, as only a small proportion of the molecules remain available following oral administration, due to insufficient gastric residence time, low permeability and/or solubility within the gut, as well as their instability under conditions encountered in food processing and storage (temperature, oxygen, light), or in the gastrointestinal tract (pH, enzymes, presence of other nutrients), all of which limit the activity and potential health benefits of the nutraceutical components, including polyphenols (Bell, 2001). The delivery of these compounds therefore requires product formulators and manufacturers to provide protective mechanisms that can maintain the active molecular form until the time of consumption, and deliver this form to the physiological target within the organism (Chen, Remondetto, & Subirade, 2006). Some physicochemical characteristics and food properties of the

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major polyphenols from different plant sources are present in Table 1, which shows their limited stability and conditioned solubility. Another unfortunate trait of polypheonls is their potential unpleasant taste, such as astringency (Table 1), which needs to be masked before incorporation into food products (Haslam & Lilley, 1988). The utilization of encapsulated polyphenols instead of free compounds can overcome the drawbacks of their instability, alleviate unpleasant tastes or flavors, as well as improve the bioavailability and half-life of the compound in vivo and in vitro. There have been a number of recent reviews or mini-reviews on the encapsulation of foods or food ingredients (Augustin & Hemar, 2009; Desai & Park, 2005; de Vos, Faas, Spasojevic, & Sikkema, 2010; Flanagan & Singh, 2006; Gouin, 2004; Jafari, Assadpoor, He, & Bhandari, 2008; Khaled & Jagdish, 2007; McClements, Decker, Park, & Weiss, 2009; Mozafari, 2005; Mozafari, 2006; Mozafari et al., 2008; Peter & Given, 2009). This review focuses on the encapsulation of the more widely used polyphenols, discussing their effectiveness, variations, developments and trends. Spray drying Spray drying encapsulation has been used in the food industry since the late 1950s. Because spray drying is an economical, flexible, continuous operation, and produces particles of good quality, it is the most widely used microencapsulation technique in the food industry and is typically used for the preparation of dry, stable food additives and flavors (Desai & Park, 2005). For encapsulation purposes, modified starch, maltodextrin, gum or other substances are hydrated to be used as the wall materials. The core material for encapsulation is homogenized with the wall materials. The mixture is then fed into a spray dryer and atomized with a nozzle or spinning wheel. Water is evaporated by the hot air contacting the atomized material. The capsules are then collected after they fall to the bottom of the drier (Gibbs et al., 1999). The typical shape of spray dried particles is spherical, with a mean size range of 10e100 mm (Fig. 2). One limitation of the spray-drying technology is the limited number of shell materials available, since the shell material must be soluble in water at an acceptable level (Desai & Park, 2005). Maltodextrins are widely used for encapsulation of flavours (Bhandari, 2007), which are also used for polyphenol encapsulation. The ethanol extracts of black carrots, which contain a high level of anthocyanins (125
17.22 mg/100 g), have been spray dried using maltodextrins as a carrier and coating agents (Ersus & Yurdagel, 2007). High air inlet temperatures (>160e180  C) caused greater anthocyanin losses, while the maltodextrin of 20e21 DE gave the highest anthocyanin content powder at the end of drying process (Ersus & Yurdagel, 2007). The maltodextrin can also be mixed with gum arabic as wall material. A mixture of maltodextrin (60%) and gum arabic (40%) has been used for encapsulation of procyanidins

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Table 1. Major polyphenols, sources and their properties. Polyphenol groups

Examples

Sources

Properties

Anthocyanidins

Cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin and their glycosides. Catechin, epicatechin, gallocatechin, epigallocatechin and epigallocatechin gallate Hesperetin, hesperidin, homoeriodictyol, naringenin, naringin Apigenin, luteolin, tangeritin

Fruit, flowers

Natural pigments; Highly sensitive to temperature, oxidation, pH, and lights; water soluble

Tea

Sensitive to oxidation, lights and pH; astringent and bitter; slightly soluble in water

Citrus

Sensitive to oxidation, lights and pH; aglycones insoluble but glycosides soluble in water Natural pigments; sensitive to oxidation and pH; aglycones slightly soluble but glycosides soluble in water Sensitive to oxidation, lights and pH; aglycones slightly soluble but glycosides soluble in water Sensitive to alkaline pH; astringent and bitter; soy smell; water soluble Sensitive to temperature, oxidation, pH, and lights; most soluble in water Sensitive to oxidation and pH; Most slightly soluble in water Relatively stable under normal conditions; unpleasant flavour; water soluble. Sensitive to high temperature and oxidation; astringent and bitter; water soluble

Catechins

Flavanones Flavones Flavonols Isoflavones Hydroxybenzoic acids Hydroxycinnamic acids Lignans Tannins (proanthocyanidines)

Kaempferol, myricetin, quercetin and their glycosides Daidzein, genistein, glycitein Gallic acid, p-hydroxybenzoic, vanillic acid Caffeic acid, ferulic acid, p-coumaric acid, sinapic acid Pinoresinol, podophyllotoxin, steganacin. Castalin, pentagalloyl glucose, procyanidins

Fruit/vegetables Fruit/vegetables Soybeans, peanuts Berries, tea, wheat Fruit, oats, rice Flax, sesame, vegetables Tea, berries, wines, chocolate

from grape seeds (Zhang, Mou, & Du, 2007). The ratio of core substance to wall material was 30:70 w/w, while the concentration of the slurry was 20% w/v. The encapsulation efficiency was up to 88.84%, and the procyanidin was not changed during drying. The stability of the products was obviously improved by spray drying. Chitosan has also been used as a wall material in spray drying of olive leaf extract (OLE) (Kosaraju, D’ath, & Lawrence, 2006). The loading percent of polyphenolic compounds was 27%, and the OLE-loaded microspheres normally had a smooth surface morphology. The FTIR spectroscopy results indicated that the majority of the OLE in the chitosan microsphere were physically encapsulated in the chitosan matrix. Chiou and Langrish (2007) introduced citrus fruit fiber as an encapsulating agent for spray drying of bioactives extracted from Hibiscus sabdariffa L. The main bioactive compounds in H. sabdariffa L. extract are polyphenols, or more specifically, the anthocyanin complexes. The presence of the bioactive material in the fibers did not appear to significantly affect the product size or shape. The results demonstrated that natural fruit fibers might be a potential replacement carrier for spray drying sticky materials. This encapsulation process combined two products (fruit fiber and polyphenols) into one multipurpose functional food, creating a novel nutraceutical product suitable for a variety of applications in functional food manufacturing (Chiou & Langrish, 2007). More recently, the effects of drying aids comprising colloidal silicon dioxide (tixosil 333), maltodextrin and starch on spray drying of soybean extract have been studied (Georgetti, Casagrande, Souza, Oliveira, & Fonseca, 2008). The resulting product, to which was added tixosil

333, showed a lower degradation of its polyphenol content and lower reduction of its antioxidant activity, suggesting that the correct selection of the drying excipients is an important step in guaranteeing the stability and the quality of the finished product. The results also indicated that the inlet gas temperature had a significant effect on the total polyphenol, protein and genistein contents of the dried extracts (Georgetti et al., 2008). Another wall material successfully used for encapsulation of polyphenol was protein-lipid (sodium caseinate-soy lecithin) emulsion, which has been used in spray drying of grape seed extract, apple polyphenol extract and olive leaf extract (Kosaraju, Labbett, Emin, Konczak, & Lundin, 2008). Optical microscopy and particle size distribution analysis indicated that the encapsulated particles all had spherical morphology and uniform size distribution. Radical scavenging activity studies demonstrated a significant retention of antioxidant activity after encapsulation by the spray-drying process (Kosaraju et al., 2008). Coacervation The concept behind coacervation microencapsulation is the phase separation of one or many hydrocolloids from the initial solution and the subsequent deposition of the newly formed coacervate phase around the active ingredient suspended or emulsified in the same reaction media (Gouin, 2004). Coacervation encapsulation can be achieved simply with only one colloidal solute such as gelatin, or through a more complex process, for example, with gelatin and gum acacia. Complex coacervation is usually associated with no definite forms (Fig. 2), and is considered an expensive method for encapsulating food ingredients

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Fig. 2. Illustration of the characteristics of encapsulated polyphenolic capsules produced by various encapsulation processes.

(Gouin, 2004); however, this process should be related to the potential benefits it might offer, especially to highvalue, labile functional ingredients, such as the encapsulation of polyphenols. Yerba mate (Ilex paraguariensis) extract (containing 62.11
1.16 mg of gallic acid/g yerba mate) has been encapsulated with two different systems: calcium alginate and calcium alginate-chitosan (Deladino, Anbinder, Navarro,& Martino, 2008). A high load of active compound (>85%) was obtained in the alginate beads but in chitosan coated beads the entrapment was lower (around 50%), on account of the active compound being lost during immersion in

chitosan. The polyphenols can be retained in a chitosan-alginate membrane, but maximum release in water was achieved in a shorter time for chitosan coated beads than with the alginate beads. These results implied that the wall materials can affect the release of the natural antioxidants of yerba mate. Gelatin is a protein containing many glycine, proline and 4-hydroxyproline residues. A new type of protein/polyphenol microcapsule based on ()-epigallocatechin gallate (EGCG) and gelatin (type A), has been produced using the layer-by-layer (LbL) assembly method (Shutava, Balkundi, & Lvov, 2009). The first layer was a gelatin layer

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over the MnCO3 microcores, over which an EGCG layer was formed by adding EGCG solution to the gelatin-coated microparticles. The MnCO3 microcores were dissolved in EDTA solution to form the stable (Gel A/EGCG)4 capsules. The EGCG content of the protein/polyphenol film material was as high as 30% w/w, while the EGCG in the LbL assemblies retained its antioxidant activity (Shutava, Balkundi & Lvov, 2009). Glucan is a polysaccharide, and also a thermoreversible gelling agent, whose gelling behavior depends on its molecular weight and concentration (Vaikousi, Biliaderis, & Izydorczyk, 2004). During cooling of the glucan water solution from 80  C to room temperature, a network structure can be formed through an interaction of the chain segment association and aggregated junction zones (Morgan & Ofman, 1998). Black currant extract has been encapsulated in glucan by simply mixing with hot dispersed glucan gel, followed by cooling and cutting into cubes, or being dropped into oil to produce a bead morphology (Xiong, Melton, Easteal, & Siew, 2006). Recovery of 73e79% of encapsulated anthocyanins was achieved using normal oven drying to dehydrate the gel matrix. Larger amounts of anthocyanins were released from cubes than from beads using the same drying process. The encapsulated anthocyanins exhibited little difference as free radical scavengers, with an increase in their reducing ability with time. Other coacervation coating systems such as gliadin, heparin/gelatin, carrageenan, soy protein, polyvinyl alcohol, gelatin/carboxymethylcellulose, b-lactoglobulin/gum acacia, and guar gum/dextran have also been studied (Gouin, 2004). However, most of the core materials in these studies were essential oils rather than polyphenols. Liposomes Liposomes were first described by Bangham and coworkers in 1965 at Cambridge University (Bangham, Standish, & Watkins, 1965). They are colloidal particles consisting of a membranous system formed by lipid bilayers encapsulating aqueous space(s) (Fig. 2). Owing to the possession of both lipid and aqueous phases, liposomes can be utilized in the entrapment, delivery, and release of water soluble, lipid-soluble, and amphiphilic materials. The underlying mechanism for the formation of liposomes and nanoliposomes is basically a hydrophilicehydrophobic interaction between phospholipids and water molecules. A major advantage of their use is the ability to control the release rate of the incorporated materials and deliver them to the right place at the right time (Scha¨fer et al., 1992). Bioactive agents encapsulated into liposomes can be protected from digestion in the stomach, and show significant levels of absorption in the gastrointestinal tract, leading to the enhancement of bioactivity and bioavailability (Takahashi et al., 2007). There are several methods for producing liposomes, and there are a number of excellent books and published reviews that provide details of the most common production techniques (Betageri & Kulkarni, 1999; Frezard, 1999;

Mozafari & Mortazavi, 2005; Mozafari et al., 2008; Watwe & Bellare, 1995). A variety of liposome techniques have been employed for the encapsulation of polyphenols. Fan, Xu, Xia, and Zhang (2007) compared the effects of five different liposome methods on the encapsulation of salidroside e thin film evaporation, sonication, reverse phase evaporation, melting, and freezing-thawing. Multilamellar vesicles can be obtained by thin film evaporation, larger unilamellar vesicles by reverse phase evaporation, and small unilamellar vesicles by sonication or extrusion technique (Bangham et al., 1965; Cevce, 1993.). The freezing-thawing treatment leads to the production of special freezing-thawing multilamellar vesicles (Maestrelli, Gonzalez-Rodriguez, Rabasco, & Mura, 2006). The encapsulating efficiency of liposomes is highest when they are prepared by freezing-thawing, followed by thin film evaporation, then reverse phase evaporation, while melting and sonication has the lowest efficiency. Loading capacity of salidroside can have significant effects on encapsulating efficiency, average diameter, and z potential of liposomes. Liposomal systems prepared by sonication, melting, and reverse phase evaporation, displayed better dispersivity. Salidroside liposomes show a slower increase in particle size than liposomes without salidroside, suggesting salidroside plays an important role in preventing the aggregation and fusion of liposomes. Fan et al. (2007) illustrated that these differences might come from the different morphologies of liposomes prepared by different methods. The nature of the core materials is another factor that affects the efficiency of liposome encapsulation. The isomers of (þ)-catechin and ()-epicatechin entrapped in liposomes show similar encapsulation levels and release rates (Fang, Hwang, Huang, & Fang, 2006). However, another type of catechin, ()-epigallocatechin-3-gallate (EGCG), has been observed to have a much higher level of encapsulation for the same liposome system. EGCG contains a galloyl group, indicating a greater lipophilicity. Hence it is possible that EGCG was stronger when to locate within the liposome bilayers, thereby increasing the entrapment. Liposome encapsulation efficiency can be increased by the addition of ethanol (15%) to the preparation hydration solution (Fang, Lee, Shen, & Huang, 2006). In response, the core material of EGCG in the liposomes showed a high rate of encapsulation of nearly 100%, compared to 84.6% encapsulation for conventional liposome. It was also shown that ethanolic solutions of phospholipids exhibit high encapsulation efficiency for both hydrophilic and lipophilic actives (Dayan & Touitou, 2000). The liposomes made in the presence of ethanol had a relatively small size of 133.1 nm. The further addition of deoxycholic acid (DA) significantly increased the size of the vesicles to 378.2 nm. EGCG encapsulated in liposomes with ethanol and DA gave a 20 fold increase in active deposition in basal cell carcinomas relative to the free form (Fang et al., 2006). The larger vesicle size of this formulation was suggested to be the predominant factor governing this enhancement.

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Evidence of liposomes enhancing the bioactivity and bioavailability of polyphenols has been reported by a number of researchers. Curcumin [1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-hepadiene-3,5-dion] is the principle curcuminoid of the popular India spice turmeric, which exhibits anti-HIV, antitumor, antioxidant, and anti-inflammatory activities (Maheshwari, Singh, Gaddipati, & Srimal, 2006). However, curcumin is poorly absorbed from the gastrointestinal (GI) tract after oral administration, due to its low water solubility and low stability against GI fluids and/or alkaline/higher pH conditions. To enhance the bioavailability and food functionality of curcumin, liposomeencapsulated curcumin (LEC) can be prepared from commercially available lecithins (SLP-PC70) and curcumin, by using a microfluidizer (Takahashi, Uechi, Takara, Asikin, & Wada, 2009). The resulting LEC is composed of small unilamellar vesicles with a diameter of approximately 263 nm, with encapsulation efficiency for curcumin of 68.0%. A faster rate and better absorption were observed for LEC relative to other forms. The results indicated that curcumin enhanced the gastrointestinal absorption by liposome encapsulation, while the plasma antioxidant activity following oral LEC was significantly higher than that of other treatments. Another example reported was quercetin liposomes prepared from egg phosphatidylcholine/cholesterol (2:1) (Priprem, Watanatorn, Sutthiparinyanont, Phachonpai, & Muchimapura, 2008). The resulting liposomes were approximately 200 nm in mean particle diameter with a negative surface charge and a range of encapsulation efficiency between 60% and 80%. Both conventional and quercetin liposomes have shown anxiolytic and cognitive-enhancing effects. A lower dose (20 mg/kg body weight day) and a faster rate of absorption were observed with intranasal quercetin liposomes when compared with oral quercetin (300 mg/kg body weight/day). The results suggested that intranasal delivery of quercetin in the form of liposomes to the brain could allow a reduction in the dose and thereby reduce the potential of toxicity of the quercetin (Priprem et al., 2008). A modified liposome system encapsulating of resveratrol has been developed, with the encapsulated particles being called “acoustically active lipospheres” (AALs) or “microbubbles” (Fang et al., 2007). The liposome is prepared using dissolved soybean phosphatidylcholine, cholesterol, coemulsifier, and resveratrol in chloroformemethanol. After evaporation of the organic solvent and rehydration, AALs are formed by stabilization using coconut oil and perfluorocarbons. The benefits of AALs are high core material loading capacity (>90%) with a small droplet size (mean diameter of w300 nm), together an acceptable level of safety, sustained core material release, and high sensitivity to ultrasound treatment. The ultrasound sensitivity of AALs is very useful, as they possess the potential to be “magic bullet” agents for the delivery of core materials to precise locations in the body, with the locations being determined by focusing the ultrasound energy.

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Inclusion encapsulation Molecular inclusion is generally achieved by using cyclodextrins (CDs) as the encapsulating materials. CDs are a group of naturally occurring cyclic oligosaccharides derived from starch, with six, seven or eight glucose residues linked by a (1-4) glycosidic bonds in a cylinder-shaped structure, and denominated as a-, b- and g-cyclodextrins, in which b- cyclodextrin is commonly applied (Pagington, 1986.) The external part of the cyclodextrin molecules is hydrophilic, whereas the internal part is hydrophobic (Fig. 2). This structure characteristic makes CDs a satisfactory medium for encapsulation of less polar molecules (such as essential oils) into the apolar internal cavity through a hydrophobic interaction (Bhandari, D’Arcy, & Padukka, 1999; Dziezak, 1998). One outstanding advantage of the inclusion of polyphenols in CDs is the effect in improving their water solubility, especially for the less water soluble phytochemicals. The inclusion of hesperetin and hesperidin in (2-hydroxypropyl)-b-cyclodextrin (HP-b-CD) (Tommasini et al., 2005), resveratrol in b-CD and maltosyl-b-CDs (LucasAbella´n, Fortea, Lo´pez-Nicola´s, & Nu´n˜ez-Delicado, 2007), olive leaf extract (rich in oleuropein) in b-CD (Mourtzinos, Salta, Yannakopoulou, Chiou, & Karathanos, 2007), quercetin and myricetin in HP-b-CD, maltosyl-b-CDs and b-CDs, (Lucas-Abella´n, Fortea, Gabaldo´n, & Nu´n˜ez eDelicado, 2008), kaempferol, quercetin and myricetin in HP-b-CD (Mercader-Ros, Lucas-Abella´n, Fortea, Gabaldo´n, & Nu´n˜ez-Delicado, 2010), 3-hydroxyflavone (3-OHeF), morin and quercetin in a- and b-CDs (Calabro` et al., 2004), rutin in b-CD (Ding, Chao, Zhang, Shuang, & Pan, 2003) have been studied, and their water solubilities improved by inclusion encapsulation. In addition, their antioxidant activities all increased in these CDs encapsulated systems. The improved antioxidant efficacy of the inclusion complex may come from the protection of the polyphenols against rapid oxidation by free radicals (Mercader-Ros et al., 2010), which may in part be explained by an increase in their solubility in the biological moiety (Ding et al., 2003). The encapsulation efficacy of CDs inclusion is affected by the core materials. Generally, the higher the hydrophobicity and smaller the molecule is, the greater the affinity for the CDs. For example, based on their relative CDs affinity, hesperetin was more effective than hesperidin (Tommasini et al., 2005), and 3-OHeF was more effective than morin or quercetin (Calabro` et al., 2004). On the other hand, different wall materials affect the encapsulation capacity for the same core material. For example, a number of studies have been reported on the encapsulation of curcumin in different CD variants (Tang, Ma, Wang, & Zhang, 2002; Tomren, Masson, Loftsson, & Tonnesen, 2007; Tonnesen, Masson, & Loftsson, 2002). It has been shown that HP-b-CD has the highest encapsulation capacity for curcumin (Tomren et al., 2007). For the core materials of quercetin and myricetin, the affinity to CDs was HPb-CD > maltosyl-b-CDs > b-CDs, reflecting the greater

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affinity of modified cyclodextrins (Lucas-Abella´n, Fortea, & Gabaldo´n, 2008) To illustrate the structures of polyphenol-CD inclusion complexes, some advanced analytical instruments were applied. The spatial configuration of the complex of rutin with b-CD has been proposed, based on NMR and molecular modeling (Ding et al., 2003), which revealed that the binding site for rutin is a single ring of rutin molecule penetrating into the b-CD cavity in the shallow position, forming a 1:1 inclusion complex. This structure can be confirmed by 1H NMR and circular dichroism spectroscopy (Calabro` et al., 2005). The structure of the inclusion complex of ferulic acid (FA) with a-CD has been analyzed by rotating frame nuclear overhouser effect spectroscopy (ROESY) (Anselmi et al., 2008). Based on this technology and modeling simulation, the insertion of the FA into the lipophilic interior of a-CD involves the -COOH and a, b-unsaturated groups and part of its aromatic moiety. The phenol and methoxyl groups of FA lie on the plane of the wider rim. This encapsulation increases the photo-stability of FA, slows FA release, and would provide safer and longer-lasting protection of the skin against solar radiation, if applied in cosmetic formulations (Anselmi et al., 2008) With the exception of CDs, other types of biopolymers have been employed in the molecular inclusion of polyphenols, such as curcumin being encapsulated in hydrophobically modified starch (HMS) (Yu & Huang, 2010). The complexed curcumin showed a 1670 fold increase in solubility, possibly reflecting the hydrophobic interaction and hydrogen bonding between curcumin and HMS. The encapsulated curcumin revealed enhanced in vitro anti-cancer activity compared to the free form. Cocrystallization Co-crystallization is an encapsulation process in which the crystalline structure of sucrose is modified from a perfect to an irregular agglomerated crystal, to provide a porous matrix in which a second active ingredient can be incorporated (Chen, Veiga, & Rizzuto, 1988). Spontaneous crystallization of supersaturated sucrose syrup is achieved at high temperature (above 120  C) and low moisture (95e97  Brix). If a second ingredient is added at the same time, the spontaneous crystallization results in the incorporation of the second ingredient into the void spaces inside the agglomerates of the microsized crystals (Fig. 2), with a size less than 30 mm (Bhandari, Datta, D’Arcy, & Rintoul, 1998). The main advantages of cocrystallization are improved solubility, wettability, homogeneity, dispersibility, hydration, anticaking, stability and flowability of the encapsulated materials (Beristain, Va´zquez, Garcı´a, & VernonCarter, 1996). Other advantages are that the core materials in a liquid form can be converted to a dry powdered form without additional drying, and the products offer direct tableting characteristics because of their agglomerated structure, and thus offer significant advantages to the candy and pharmaceutical industries (Desai & Park, 2005). Deladino, Anbinder, Navarro, and Martino (2007) reported on the encapsulation of yerba mate (I. paraguariensis)

extract containing caffeoyl derivatives and flavonoids, by cocrystallization in a supersaturated sucrose solution. The co-crystallized product had a typically cluster-like agglomerate structure with void spaces and a sucrose crystal size varying between 2 and 30 mm. An extra layer of a network with neat edges covered the crystals. The microstructure was further confirmed by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy (Deladino, Navarro, & Martino, 2010). The cocrystallization of yerba mate extract changed it from a cohesive material to be a non-cohesive product, and notably reduced its hygroscopic characteristics without affecting its high solubility; this demonstrated that cocrystallization is a good alternative for the preservation and handling of yerba mate extract for further application in food products. There have been very few reports of the application of the cocrystallization process. Nanoencapsulation Nanoencapsulation involves the formation of activeloaded particles with diameters ranging from 1 to 1000 nm (Reis, Neufeld, Ribeiro, & Veiga, 2006). The term nanoparticle is a collective name for both nanospheres and nanocapsules. Nanospheres have a matrix type of structure. Actives may be absorbed at the sphere surface or encapsulated within the particle. Nanocapsules are vesicular systems in which the active is confined to a cavity consisting of an inner liquid core surrounded by a polymeric membrane (Fig. 2) (Couvreur, Dubernet, & Puisieux, 1995). The active substances are usually dissolved in the inner core but may also be adsorbed to the capsule surface (Alle´mann, Gurny, & Doekler, 1993). It is proposed that any target actives, while incorporated into a complex of polymers, which result in nanoscalesized particles, might be called ‘encapsulated nanoparticles’. Compared to micron-sized particles, nanoparticles provide a greater surface area and have the potential to increase solubility due to a combination of large interfacial adsorption of the core compound, enhanced bioavailability, improved controlled release, which enable better precision targeting of the encapsulated materials (Mozafari et al., 2008). A variety of techniques have been employed to develop polyphenol nanoparticles. Barras et al. (2009) describe the loading of quercetin and EGCG by lipid nanocapsules (LNC) through the application of the phase inversion process. Briefly, the actives were mixed in the oil phase prior to preparation. Soybean lecithin, surfactant, NaCl and distilled water were then mixed and heated to form a W/O emulsion. The mixture was cooled, and distilled cold water (0  C) added, with stirring to form O/W nanocapsules. The benefits of this method are that the average volume sizes of particles are a function of the formulation composition, which means the LNC size can be tailored by formulation design. The higher encapsulated quercetin LNC increased its apparent aqueous solubility by a factor of 100. The encapsulated quercetin and

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()-EGCG have proved to be more stable compared to the free ones. The nanoprecipitation technique has been used for curcumin entrapment, based on poly (lactide-co-glycolide) (PLGA) and a stabilizer polyethylene glycol (PEG)-5000 (Anand et al., 2010). The nanoprecipitation technique involves three steps: First, the target actives and a polymer are mixed in an organic solution; second, the mixture is added, drop wise, to an aqueous solution, normally containing a surfactant; third, the resulting dispersion of nanoparticles is vacuum evaporated to eliminate the organic solvent, and then centrifuged or filtered to obtain the particles. In the case of curcumin-loaded nanoparticles, the encapsulation efficiency was reported to have reached 97.5%, with the particle diameter being about 80.9 nm, which enhanced its cellular uptake, and increased in vitro bioactivity, resulting in superior in vivo bioavailability over free curcumin (Anand et al., 2010). Other quercetin loaded nanoparticles were developed by using a similar technique, with a particle size of <85 nm, and encapsulation efficiency of over 99% (Wu et al., 2008). The encapsulated active of quercetin might have an amorphous state, which formed intermolecular hydrogen bonding with carriers. The release of the nanoparticals was 74-fold times higher when compared with the pure active, and possessed more effective antioxidant activities. A method based on the concept of emulsionediffusioneevaporation, using polyethylene glycol (PEG) 400 as a co-solvent, has been applied on ellagic acid (EA) loaded PLGA nanoparticles (Bala, Bhardwaj, Hariharan, Kharade, Roy, & Ravi Kumar, 2006). Didodecyldimethylammomium bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with chitosan (CS), were used as the stabilizer. The basis of this technique is as follows: the stirring of the EA-PLGA-PEG 400 mixture causes the dispersion of the solvent in the form of irregularly sized droplets in equilibrium with the continuous phase, while the stabilizer is adsorbed on to the larger interface, thereby creating the first emulsion stage; then, the homogenization results in smaller droplets with more homogenous size distribution; the addition of water and subsequent heating destabilizes the equilibrium and causes the organic solvent to diffuse into the aqueous phase and then out of the system, leading to precipitation of the polymer along with the active as very small particles (Kumar, Bakowsky, & Lehr, 2004). The initial release of EA from nanoparticles in pH 7.4 phosphate buffer is rapid, followed by a slower sustained release. An in situ intestinal permeability study in rats showed a higher uptake of active encapsulated in nanoparticles prepared using PVA, PVAeCS blend and DMAB as stabilizers, than pure active (Bala et al., 2006). Resveratrol is incorporated into amphiphilic copolymers of mPEGePCL (methoxy poly(ethylene glycol)-poly(caprolactone)), with an active loading content of 19.4
2.4% and an encapsulation efficiency of >90%

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(Shao et al., 2009). The mPEGePCL based nanoparticles are composed of a hydrophilic segment and a hydrophobic segment, which are capable of loading the target active by self assembling into nanoscale spherical structures with a hydrophilic outer shell and a hydrophobic inner core (Liu et al., 2008). In this way, lipophilic actives can be entrapped into the hydrophobic core of the nanosphere, while its hydrophilic outer shell is maintained as a stabilizer for the system. Other actives with lipophilicity can also be incorporated into this nanoparticle system to enhance their bioavailability. Tea catechins have been successfully encapsulated in chitosan- tripolyphosphate (CS-TPP) nanoparticles using a simple ionotropic gelation method (Hu et al., 2008). By controlling the critical fabricating parameters of the CS molecular mass, CS concentration, and CS-TPP mass ratio, desirable CS-TPP nanoparticles can be spontaneously formed when the freshly prepared CS solution containing tea catechins is added with TPP solution, while stirring at room temperature (Hu et al., 2008). In comparison with this simple method, a relatively complicated method has been developed for the encapsulation of polyphenols of EGCG, tannic acid, curcumin, and theaflavin (Shutava, Balkundi, Vangala et al., 2009). First, gelatin nanoparticles are prepared using a twostep desolvation method. These particles are then further encapsulated in polyelectrolytes using a layer-by-layer shell assembly method. Finally, the polyphenols are loaded into the prepared nanoparticles by adsorption under certain pH values. The adsorption of polyphenols to the nanoparticles depends on the chemical nature of the molecules. Adsorption of polyphenols with higher molecular weights and a larger number of phenolic -OH groups was found to be higher. The amount of theaflavin, the polyphenol with the highest molecular weight among those investigated, was as high as 70% of the mass of nanoparticle solid material. Loading of tannic acid and EGCG is lower, while it is almost negligible for curcumin (Shutava, Balkundi, Vangala et al., 2009). Freeze drying Freeze drying, also known as lyophilization or cryodesiccation, is a process used for the dehydration of almost all heat-sensitive materials and aromas. Freeze-drying works by freezing the material and then reducing the surrounding pressure and adding enough heat, to allow the frozen water in the material to sublimate directly from the solid phase to the gas phase (Oetjen & Haseley, 2004). Encapsulation by freeze drying is achieved as the core materials homogenize in matrix solutions and then co-lyophilize, usually resulting in uncertain forms (Fig. 2). Except for the long dehydration period required (generally 20 h), freeze-drying is a simple technique for encapsulating water-soluble essences and natural aromas, as well as drugs (Desai & Park, 2005). Freeze dried samples of pomace containing anthocyanin and maltodextrin DE20 have shown good shelf life stability during storage at 50  C/0.5 water activity for up to two months (Delgado-Vargas, Jimenez,

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& Pardes-Lopez, 2000). Recently, Laine, Kylli, Heinonen, and Jouppila (2008) encapsulated phenolic-rich cloudberry extract by freeze drying, using maltodextrins DE5-8 and DE18.5 as wall materials. The microencapsulated cloudberry extract offered better protection for phenolics during storage, while the antioxidant activity remained the same or even improved slightly. However, there is also some evidence of freeze drying induced encapsulation being unable to improve stability or bioactivity. When Hibisus anthocyanin extract was encapsulated in pullulan by freeze drying, it was only when samples stored at higher relative humidity levels (aw>0.75) that the free anthocyanins showed w1.5e1.8 times faster degradation than the pullulan-anthocyanin colyophilized materials (Gradinaru, Biliaderis, Kallithraka, Kefalas, & Garcia-Viguera, 2003). Obviously, this was not a big difference. Furthermore, both free and co-lyophilized with pullulan, Hibiscus anthocyanins exhibited good antiradical activity throughout storage, and no significant differences were observed between them, suggesting that the encapsulation might not be necessary if the Hibisus anthocyanin extract is to be freeze dried.

Yeast encapsulation Encapsulation of essential oils and flavours by using yeast cells (Saccharomyces cerevisiae) as wall material have proven to to be a low cost, high volume process (Bishop, Nelson, & Lamb, 1998). Yeast encapsulation depends on the yeast cells, which allow the actives to pass freely through the cell wall and membrane, while remaining passively within the cells (Fig. 2). Encapsulation by yeast cells can control the diffusion of actives through the cell wall and membrane, using a defined temperature and time, in a pre-determined solution mix, with the wall of the yeast cells providing protection of the liquid active ingredients against evaporation, extrusion, oxidation and light (MICAP PLC, 2004).This technology has been typically used for encapsulation of small lipophilic molecules such as essential oils. The yeast cells have proved to be able to absorb and retain water-soluble flavor compounds when pre-treated with a plasmolyser (Serozym Laboratories, 1973). This technique has been adopted in water soluble polyphenol encapsulation. After treatment with 5% sodium chloride at 54  C for 24 h for autolysis, the yeast cells can be used to encapsulate water soluble polyphenol of chlorogenic acid, with an encapsulation efficiency of 12.6% (Shi et al., 2007). The yeast encapsulated chlorogenic acid was found to be highly stable under wet and thermal stresses, with the release profiles suggesting that the yeast cells could prevent chlorogenic acid from change, without significantly slowing down the release. Another obvious benefit of this technique is that no additives apart from water, yeast and core materials are used during processing, thereby ensuring its safety in the food industries (Blanquet et al., 2005).

Emulsions Emulsion technology is generally applied for the encapsulation of bioactives in aqueous solutions, which can either be used directly in the liquid state or can be dried to form powders (e.g., by spray, roller, or freeze drying) after emulsification. Therefore it is actually a part of encapsulation process. Basically, an emulsion consists of at least two immiscible liquids, usually as oil and water, with one of the liquids being dispersed as small spherical droplets in the other (Friberg, Larsson, & Sjoblom, 2004; McClements, 2005). Typically, the diameters of the droplets in food systems range from 0.1 to100 mm (McClements et al., 2009). Emulsions can be classified according to the spatial organization of the oil and water phases. A system that consists of oil droplets dispersed in an aqueous phase is called an oil-in-water (O/W) emulsion, whereas a system that consists of water droplets dispersed in an oil phase is called a water-in-oil (W/O) emulsion (Fig. 2). With the exception of the simple O/W or W/O systems, various types of multiple emulsions can be developed, such as oil-in-water-in-oil (O/W/O) or water-in-oil-in-water (W/O/W) emulsions (Benichou, Aserin, & Garti, 2004; van der Graaf, Schroen, & Boom, 2005). To obtain a kinetically stable solution, stabilizers such as emulsifiers or texture modifiers, are commonly added in the emulsion systems. The use of this technology for delivering food components and nutriceuticals has been comprehensively reviewed by Augustin and Hemar (2009), Flanagan and Singh (2006) and McClements et al. (2009). A US patent named “functional emulsions”, relates to dissolved polyphenols in ethanol (polyglycerol oleic acid ester added), which are then stirred with vegetable oil in a homogenizer, or emulsified, to obtain E/O type or E/O/W type emulsions (Nakajima, Nabetani, Ichikawa, & Xu, 2003). These emulsions can be used in pharmaceutical, nutriceutical or food industries as polyphenol delivery systems. Naturally these polyphenols are insoluble or have low solubility in water and oil, so the obvious advantage of these emulsions is that they contain a high concentration of polyphenols. Most recent researches in relation to polyphenol emulsions have been used for the reduction of lipid oxidation or increase lipid stability. In one study, after dissolving Tween 20 in water containing lyophilized tea infusion and bovine serum albumin (BSA), sunflower oil (from which tocopherols has been removed) was added dropwise to the aqueous sample in an ice bath and sonicated for 5 min (Almajano, Carbo´, Jime´nez, & Gordon, 2008). The W/O emulsions containing tea extracts have shown strong antioxidant activity against oil oxidation. Another W/O emulsion prepared by the same research group using a similar method but containing caffeic acid as an antioxidant and Fe (III) as a pro-oxidant ion, also noted the antioxidant activity of caffeic acid (Almajano, Carbo´, Delgado, & Gordon, 2007). However, when different polyphenols were used in the W/O emulsions, their antioxidant activities showed different characteristics. In the Tween 20-phosphate buffer-olive oil emulsion system, gallic acid can

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Table 2. Technologies for encapsulation of polyphenols. Encapsulation Technologies Spray Drying Wall materials: Maltodextrins Maltodextrin and gum arabic Chitosan Citris fruit fiber Colloidal silicon dioxide, maltodextrin and starch Sodium caseinate-soy lecithin Coacervation Wall materials: Calcium alginate and calcium alginateechitosan Gelatin (type A) Glucan Liposome Specific methods: Thin film evaporation, sonication, reverse phase evaporation, melting, and freezing-thawing Thin film evaporation Using microfluidizer Lipid thin film formation and extrusion Thin film evaporation and sonication Inclusion encapsulation Wall materials: HP-b-CD b-CD and maltosyl-b-CDs b-CD HP-b-CD, maltosyl-b-CDs and b-CDs HP-b-CD a- and b-CDs b-CD HP- b-CD HP- b-CD, maltosyl-b-CDs, b-CDs, b-CD a-CD hydrophobically modified starch Cocrystallization Freeze drying Wall materials: Maltodextrin DE20 Maltodextrins DE 5-8 and DE18.5 Pullulan Nanoencapsulation Specific methods: Phase inversion Nanoprecipitation Nanoprecipitation Emulsionediffusioneevaporation Amphiphilic copolymers Ionotropic gelation Adsorption to prepared nanoparticles (layer-by-layer assembly) Yeast cells Emulsions Systems: Tween 20-BSA- Fe (III)- sunflower oil O/W emulsion Tween 20-BSA- sunflower oil O/W emulsion Tween 20-phosphate buffer-olive oil O/W emulsion

Polyphenols

References

black carrot extracts (anthocyanins) procyanidins olive leaf extract Hibiscus sabdariffa L. extract (anthocyanins) soybean extract grape seed extract, apple polyphenol extract and olive leaf extract

Ersus & Yurdagel, 2007 Zhang et al., 2007 Kosaraju et al., 2006 Chiou & Langrish, 2007

yerba mate extract EGCG black currant extract

Deladino, Anbinder, Navarro, & Martino, 2008 Shutava et al., 2009a Xiong et al., 2006

salidroside

Fan et al., 2007

(þ)-catechin, ()-epicatechin, EGCG curcumin quercetin resveratrol

Fang, Hwang, Huang, & Fang C.-C, 2006a Takahashi et al., 2009 Priprem et al., 2008 Fan et al., 2007

hesperetin and hesperidin resveratrol olive leaf extract (rich in oleuropein) quercetin and myricetin kaempferol, quercetin and myricetin 3-hydroxyflavone, morin and quercetin rutin curcumin quercetin and myricetin rutin ferulic acid curcumin

Tommasini et al., 2005 Lucas-Abella´n et al., 2007 Mourtzinos et al., 2007 Lucas-Abella´n et al., 2008 Mercader-Ros et al., 2010 Calabro` et al., 2004 Ding et al., 2003 Tomren et al., 2007 Lucas-Abella´n et al., 2008 Ding et al., 2003 Anselmi et al., 2008 Yu & Huang, 2010

Yerba mate extract

Deladino et al., 2007

anthocyanin cloudberry extract Hibisus anthocyanin

Delgado-Vargas et al., 2000 Laine et al., 2008 Gradinaru et al., 2003

quercetin and EGCG curcumin quercetin ellagic acid resveratrol tea catechins EGCG, tannic acid, curcumin, and theaflavin

Barras et al., 2009 Anand et al., 2010 Wu et al., 2008 Bala et al., 2006 Shao et al., 2009 Hu et al., 2008 Shutava et al., 2009b

chlorogenic acid

Shi et al., 2007

caffeic acid Tea extract Gallic acid, catechin, quercetin

Almajano et al., 2007 Almajano et al., 2008 Di Mattia et al., 2009

Georgetti et al., 2008 Kosaraju et al., 2008

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stabilise the colloidal properties towards physical instability, while showing low activity towards secondary oxidation. Catechin showed an interfacial localisation which was reflected in the enhancement of primary oxidation and in the inhibition of secondary oxidation. Quercetin was poorly partitioned in the aqueous phase and had no effect on slowing down the bimolecular phase of auto-oxidation (Di Mattia, Sacchetti, Mastrocola, & Pittia, 2009). These results suggested that not only polarity but also antioxidant activity, can affect the polyphenol protective role towards lipids auto-oxidation in emulsions.

Summary and trends The abundant work on encapsulation of polyphenols is summarized in this paper. The characteristics of capsules produced by the various encapsulation processes are illustrated in Fig. 2, which also shows that the different morphologies can be achieved by these techniques. All of the work reported and summarized in this paper, has been undertaken since the year 2000 (Table 2), with the research and related reporting indicating the current worldwide interest in the subject. From the literature, it is clear that the utilization of encapsulated polyphenols instead of free compounds, can lead to improvements in both the stability and bioavailability of the compounds in vivo and in vitro, and optimize routes for their administration. Although most of the encapsulation technologies employed for other chemicals have been adopted in polyphenol encapsulation, there are still some technologies not being applied for these special phytochemicals, including spray cooling/chilling, spinning disk and centrifugal coextrusion, extrusion and fluidized bed. However, this does not necessary mean that these technologies are not suitable for polyphenol encapsulation. Because there is still a lack of direct evidence for the use of polyphenols in preventing and treating of human diseases (Scalbert, Manach et al., 2005), most of the polyphenol encapsulated particles are classified as ‘functional foods’ or ‘nutriceuticals’, which limits their potential markets. In food grade products, cost is an important factor for their industrialization. Yeast encapsulation of chlorogenic acid is an example of a successful low cost but high volume processing (Shi et al., 2007). Future research of polyphenol encapsulation is likely to focus on aspects of delivery and the potential use of co-encapsulation methodologies, where two or more bioactive ingredients can be combined to have a synergistic effect. It can be foreseen that, with a deep understanding of the health benefits of polyphenols, improvements in manufacturing technologies, new strategies for stabilization of fragile nutraceuticals, and the development of novel approaches to site-specific carrier targeting, encapsulated polyphenols will play an important role in increasing the efficacy of functional foods or even pharmaceuticals, over the next decade.

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