Isoprenoids (terpenes) are formed by coupling of isoprene (2-methylbutadiene) units in a pattern called head-to-tail joining, and their structure contains a multiple of five carbon atoms (Mann et al., 1994; Baser and Buchbauer, 2010). Hence, the structural classification of terpenes is based on the number of isoprene units in a molecule. Hemiterpenes are built from one isoprene unit (C5); monoterpenes contain 10 carbons (C10), and sesquiterpenes contain 15 (C15), whereas diterpenes contain 20 (C20). Functional characterization depends on cyclic or linear structure, degrees of unsaturation, or type of substituents (hydrocarbons, alcohols, ethers, oxides, aldehydes, ketones, esters). The term terpenoids is restricted to isoprenoids bearing oxygen moiety (Baser and Buchbauer, 2010; Moghaddam and Mehdizadeh, 2017). Some molecules presented in EOs are the degradation products of larger, usually not volatile structures. Norisoprenoids are degradation products resulting from the enzymatic or non-enzymatic cleavage of triterpenoids or tetraterpenoids. Ionones, damascones, or megastigmanes result from degradation of the central part of the chain of carotenoids, whereas irones are the degradation products of triterpenoid iripallidal (Fleischmann and Zorn, 2008; Baser and Buchbauer, 2010).

The basic structure in shikimate derivatives is C6–C3 unit of benzene ring (C6) linked usually to three-carbon side chain (C3) at position 1 and oxygenated in the third/fourth/fifth position/s. C3 often possess a carbon–carbon double bond; however, the side chain can also be shortened to one carbon (C1). Phenols or phenol ethers are phenylpropanoids frequently found in EOs (Baser and Buchbauer, 2010; Moghaddam and Mehdizadeh, 2017).

Fatty acid derivatives found in EO are formed in condensation reactions of polyketides, degradation of lipids or cyclization of arachidonic acid (Dudareva et al., 2006). Condensation of polyketides results in formation of phenolic rings, which are oxidized on alternate carbon atoms, either as acids, ketones, phenols, or as one end of a double bond (Baser and Buchbauer, 2010). The array of enzymatic reactions on fatty acids, such as cleavage, oxidation, lactonization, reduction, or elimination, gives rise to short-chain lactones, alcohols, or aldehydes, whereas cyclization or arachidonic acid results in production of prostaglandins and jasmonates (Dudareva et al., 2006; Baser and Buchbauer, 2010).

Amino acids, such as alanine, valine, leucine, isoleucine, and methionine, are the precursors of aldehydes, alcohols, esters, acids, and nitrogen- and sulfur-containing constituents of EOs (Dudareva et al., 2006). Sulfur compounds (sulfides, disulfides, trisulfides, sulfoxides, and isothiocyanates), as well as heterocyclic compounds containing nitrogen (indole, methyl anthranilates, pyridines, and pyrazines) or oxygen (lactones, coumarins, and furanoids) in a ring, are rarely found in EOs. These molecules have relatively simple structures and intensive characteristic or pungent odor (Moghaddam and Mehdizadeh, 2017). Some examples of the main groups of EO constituents are presented in Figure 2.

The basic characteristic of EOs is their odor. Constituents of EOs are partly in the vapor state due to high vapor pressure at atmospheric pressure and at room temperature (Dhifi et al., 2017). Higher number of carbon atoms in the structure results in decreased volatility. The highest boiling points have monoterpenes; hence, compounds from this class are highly volatile and evaporate quickly. Sesquiterpenes are still sufficiently volatile to be present as EOs; however, diterenes are less frequently found in volatile fractions (Baser and Buchbauer, 2010).

The distillation of plant material usually yields a transparent, colorless, or pale yellow liquid, immiscible with water and having density lower than water. However, some exceptions are known. Solid or semisolid EOs are obtained from orris and guaiac wood or plumeria, respectively. Chamomile gives blue EO; and European valerian, green; and vetiver, brown, whereas cinnamon gives yellow to brownish. Cinnamon, sassafras, and vetiver EOs have density equal to or near one, relative to water (Dhifi et al., 2017; Moghaddam and Mehdizadeh, 2017). Essential oils are soluble in fats, alcohols, and most organic solvents. Their constituents contain asymmetric carbons, what results in optical activity (optical rotation). They are also characterized by refractive index (Moghaddam and Mehdizadeh, 2017). Density, optical rotation, and refractive index are the parameters used to control quality of EOs. Their correct determination is described in standards published by ISO¹ (ISO/TC 54: ISO 279:1998; ISO 280:1998; ISO 592:1998), and the range of acceptable values is provided for most commercially available EO. Basic physical characteristics of some terpene compounds and EOs are provided in Tables 1, 2, respectively.

During release from plant structures (ducts or glands), volatiles become susceptible to temperature, light, oxidation, or hydrolysis. The final composition of EOs depends not only on chemical composition of plant material, but also on plant material processing and storage, distillation processes, and subsequent handling of EOs (Turek and Stintzing, 2013; Moghaddam and Mehdizadeh, 2017). The major factor influencing stability of EOs is the chemical character of their constituents. Compounds containing double bonds are prone to autoxidation because hydrogen atom abstraction results in resonance-stabilized radicals. Polyunsaturated terpenic hydrocarbons can form radicals stabilized by conjugated double-bonds. At the same time, isomerization to tertiary radicals can take place, leading to oxidative deterioration (Turek and Stintzing, 2013). The access to aerial oxygen causes the spontaneous free radical chain reactions, resulting in production of unstable hydroperoxides, which decompose in the presence of light, heat, or upon increasing acidity. Monovalent to polyvalent alcohols, aldehydes, ketones, epoxides, peroxides, acids, or oxygen-bearing polymers are stable secondary oxidation products. Some oxygen-bearing terpenoids are, however, directly converted into oxidized secondary products without hydroperoxides formation (Geier, 2006; Turek and Stintzing, 2013). Because the oxygen present in headspace diffuses into the sample over storage time, the EOs should be kept in completely filled containers or, if possible, should be treated with inert gas to remove remaining air and prevent oxidative reactions (Geier, 2006; Turek et al., 2012). The two other factors strictly correlated with oxidative deterioration of EOs are light and temperature. Light accelerates autoxidation and formation of alkyl radicals, catalyzes intramolecular isomerization reactions or trans–cis conversions in monoterpenes, and increases the degradation of monoterpenes (Turek and Stintzing, 2013). Heat accelerates chemical reactions and contributes to formation of primary auto-oxidation products—hydroperoxides, which are subsequently decomposed with increasing temperature, resulting in final oxidation products (Turek and Stintzing, 2012, 2013; Turek et al., 2012). Volatiles are thermolabile and susceptible to rearrangement processes at elevated temperatures. Thermal degradation of terpenes is classified into four types of oxidative reactions: cleavage of double bonds, epoxidation, dehydrogenation into aromatic systems, and allylic oxidation into alcohols, ketones, and aldehydes (McGraw et al., 1999). Because oxygen solubility is lower at elevated temperatures, alkyl or hydroxyl radical formation is more pronounced. On the other hand, storage of EOs at low temperatures favors the solubility of oxygen in liquids and results in peroxide formation (Turek and Stintzing, 2013). In complex mixtures, such as EOs, compounds easily undergo oxidation, predominantly isoprenoids, affecting more stable structures initiating their rearrangement and decomposition reactions. In return, phenylpropanoids present as EOs act as antioxidants able to scavenge free radicals and to protect other molecules from deterioration (Turek and Stintzing, 2013). As a result of decomposition processes described above, EOs are losing their quality. The most evident signs of aging are changes in colors, consistency, and odor, and at the last being as unpleasant and often pungent.

General physicochemical features of EOs (complexity and interactions of individual compounds) and their constituents (low molecular weight, presence of different functional groups in the molecule, reactivity, and hydrophobicity) strongly affect the biological activity of EOs.

Bioavailability and bioaccessibility of plant metabolites, including EOs and their individual terpene compounds, are studied by different in vivo and in vitro methods. In vitro digestion models are commonly used for bioaccessibility estimation. The most of these methods simulate the conditions of gastrointestinal (GI) system by adjusting the pH and introduction of particular digestive enzymes (e.g., salivary amylase, pepsin, gastric lipase, trypsin, chymotripsin, pancreatic lipase, etc.), bile salts, and, sometimes involving fermentation reactions to reproduce the colon performance (Jones et al., 2019). Recent in vitro bioaccessibility/bioavailability studies include cell models, primarily Caco-2 cells isolated from the human colorectal adenocarcinoma, where absorbed target compound is collected on the basolateral side of the monolayer model cells (Jones et al., 2019; Thakur et al., 2020). Bioavailability studies have been also performed by in vivo animal and clinical studies.

As for the other drugs, bioavailability of EOs and their compounds represents the concentration threshold reaching the blood circulation system and includes digestion (in case of oral administration), absorption, transformation (metabolism), tissue distribution, and bioactive performance at the target sites (Carbonell-Capella et al., 2014).

Bioavailability comprises pharmacodynamic and pharmacokinetic performances of bioactive compounds. Pharmacodynamics of EOs includes effects of their individual compounds on human and animal biochemical and physiological processes, i.e., should include the monitoring of biological activity at target organs, tissues, and cells. Independently of low selectivity of EOs, their bioactive effects are expressed after reaching the blood circulation.

Pharmacokinetics of EOs in fact reflects the destiny of each individual compound from the intake toward final elimination from the body, referring different processes of bioaccessibility and bioavailability.

The primary intake routes of EOs are skin application, inhalation, and oral intake.

Various factors affect the bioavailability of EOs, such as physiochemical, biochemical, and physiological interactions. The comprehension of bioavailability of EOs includes the monitoring of successive phases of their absorption, distribution, and excretion in the human body. There is limited information on their behavior and fate in human, and most studies are performed either in vitro (e.g., Volić et al., 2018) or on animal models (e.g., Michiels et al., 2008; Zhang Y. et al., 2014). It is assumed that bioavailability of EOs is maximal (100%) by intravenous administration and decreases upon other administration routes. However, the bioavailability of EO constituents orally administrated might be very high, as reported for 1,8-cineole with bioavailability rate of 95.6% (Zimmermann et al., 1995).

Nevertheless, recent reports confirm that most EOs are rapidly absorbed under dermal, oral, or pulmonary administration. To assume the bioavailability and especially the bioactivity of EOs, it is necessary to know how and in which amount they could enter the blood circulation and how they are distributed within the body, all reflecting the safety issues of EOs (Tisserand and Young, 2014).

To enhance bioavailability, the bioactive compound should exhibit sufficient absorption and low (renal) clearance, i.e., excretion ability. As soon as an EO component comes in the bloodstream, the body begins to modify it, i.e., to break it into the smaller and more polar molecules for easier kidney filtration and elimination (Djilani and Dicko, 2012).

Liver metabolism includes transformation processes of oxidation and hydroxylation, as well as adding of some polar accessories, known as phase I (metabolism via the cytochrome P450 path) and phase II (glucuronidation, sulfation, and glutathione conjugation), respectively. Metabolic fate is highly dependent on the chemical nature of EOs and their individual compounds. Essential oil metabolites of phase II were found in human and animals, in form of glucoronides and sulfates, whereas excreted metabolites are mainly glycine and glucuronic acid or are exhaled as CO₂ (Kohlert et al., 2002). Terpenes are distributed from blood circulation to other tissues. Because of high clearance and short elimination half-life, their accumulation is doubtful. It was shown that, after oral administration of menthol, 35% of the original amount of the compound was excreted renally as menthol glucuronide, the major biliary metabolite able to enter enterohepatic circulation (e.g., Kohlert et al., 2000; Grigoleit and Grigoleit, 2005). The similar was reported for thymol, carvacrol, limonene, and eugenol. After oral intake of EOs, sulfate and glucuronide metabolites have been found in urine and in plasma, respectively (Guénette et al., 2007; Michiels et al., 2008).

Lipophilic substances, such as EO components, are able to penetrate the blood–brain barrier and to interact with various brain receptors, such as γ-aminobutyric acid and glutamate receptors (Tisserand and Young, 2014). Monoterpenes and sesquiterpenes would be expected to spend a short time in the bloodstream before being redistributed first to muscle and then over a longer period to fat (Tisserand and Young, 2014). However, it is known that EO compounds are easily absorbed, and only a small portion of the EO remains unchanged (e.g., Kohlert et al., 2000; Djilani and Dicko, 2012), independently on administration route. The fast metabolism and short half-life of active compounds of EOs ensure minimum risk of their accumulation in body tissues (Kohlert et al., 2002).

Characteristic and distinctive properties of EOs and their constituents relating their physicochemical characteristics, bioavailability, and especially biological effects at the target site are a crucial point for the determination of appropriate carrier system and related encapsulation technique.

Polysaccharides, such as alginate, chitosan, and maltodextrin, are widely used in the form of physical or chemical hydrogels for encapsulation of EOs (Ravichandran et al., 2014; Gomez-Mascaraque et al., 2015; Pasukamonset et al., 2016). Alginate is a common name for a whole family of natural, water-soluble, linear macromolecules of high molecular mass (between 32,000 and 400,000 g/mol) primarily extracted from brown algae species. The distribution of mannuronic acid and guluronic acid units in alginate chain containing blocks of G-G, M-M, and M-G residues [where G is α-l-gluronic acid, and M is β-d-mannuronic acid Milivojevic et al., 2015], as well as their ratio (M/G), depends on the natural source of alginate (type of algae, season, location etc.) and predominately determine their physical and chemical properties. Chitosan is composed mainly of (1, 4) linked 2-amino-2-deoxy-d-glucan. Similarly as alginate, the chitosan chains also behave as semiflexible chains. Anion-like alginate chains spontaneously form gel with cation-like chitosan chains at pH 7.0 with various rheological behavior, depending on the alginate-to-chitosan ratio. Maltodextrin is extracted from starch by partial hydrolysis. This type of polysaccharide consists of d-glucose units connected in chains of variable length.

Ca–alginate has been proposed in order to improve bioavailability, thermal stability, and biological activity of active compounds under simulated GI conditions (Cho et al., 2014; Pasukamonset et al., 2016). However, undesirable leakage of EOs could be resulted by weak interactions between active compounds and hydrogel matrix. In order to improve the carriers performances, Ca–alginate beads could be coated with chitosan. The additional stability of carriers is provided by formation of alginate–chitosan complexes (Popa et al., 2000; Anbinder et al., 2011). Devi and Maji (2009) used chitosan–carrageenan carriers to encapsulate neem EO. Neem seed oil is a commercialized product derived from fruits of the neem tree, also named margosa oil. Microencapsulation of pimento EO in chitosan and k-carrageenan ensures antimicrobial activity against various bacteria, such as Candida utilis, Bacillus cereus, and Bacillus subtilis (Dima et al., 2014). Dong et al. (2011) used gum Arabic as carriers for microencapsulation of peppermint EO. Prolonged release of peppermint EO (and its major compounds, mainly menthol and isomenthol) is ensured by encapsulation (Sarkar et al., 2013).

Maltodextrin is a hydrolyzed starch commonly used for microencapsulation of EOs in combination with surface active biopolymers, such as gum Arabic (Fernandes et al., 2008; Bule et al., 2010; Kausadikar et al., 2015), modified starches (Bule et al., 2010), and proteins (Hogan et al., 2003; Bae and Lee, 2008) in order to ensure an effective encapsulation by spray drying process. It is in accordance with the fact that maltodextrin provides good thermal stability and protection against oxidation. However, this polysaccharide ensures low emulsifying capacity. Consequently, it is desirable to mix maltodextrin with surface-active biopolymers in order to advance the volatile retention of bioactive compounds during the drying process (Ersus and Yurdagel, 2007; Fang and Bhandari, 2010; Paz et al., 2010; Mahadivi et al., 2016; Tolun et al., 2016). Composite made by gum Arabic, modified starch, and maltodextrin has been used for microencapsulation of cardamom EO in order to increase the stability of components, such as 1,8-cineole and α-terpinyl acetate (Krishnan et al., 2005). Kanakdande et al. (2007) used similar carriers for microencapsulation of cumin oleoresin. They reported that cumin volatile EO consists of terpenes (such as β-pinene, p-cymene, and γ-terpinene), aldehydes (cuminaldehyde, 1,3-pmentha, and 3-p-menthen-7-al), and terpene alcohol. Oxygen barrier properties of maltodextrin depend on the dextrose equivalent (DE). Carriers with higher DE ensure intensive interactions between active compounds and matrix, which ensure higher encapsulation efficiencies. These carriers are less permeable to oxygen.

Maltodextrin with high DE has been successfully utilized in the encapsulation of lemon EO, orange peel EO, cardamom EO, and ginger EO to protect it from oxidation (Touré et al., 2011; Simon-Brown et al., 2016). Recently, it was shown that maltodextrin as carrier material has also an ability to provide protection of the polyphenol compounds against enzyme actions in simulated GI conditions (Romano et al., 2017). The xanthan gum, an extracellular microbial polysaccharide, has been used as a carrier for antioxidants and phenolic compounds (Da Rosa et al., 2013; Rutz et al., 2013). Xanthan gum has potential to be used as a carrier material in combination with maltodextrin and chitosan in order to ensure strong electrostatic interactions, between the amino groups of chitosan (polycation) and the carboxylic groups of xanthan (polyanion). This type of blend carriers has demonstrated improvement in the controlled release rate of encapsulated ingredient (Martínez-Ruvalcaba et al., 2007; Da Rosa et al., 2013). It was also reported that the biopolymer complexes of xanthan gum and whey proteins have emulsifying power and also the positive effect on the control release of water-soluble nutraceuticals in the delivery systems type of W/O/W double emulsions (Benichou et al., 2007; Prichapan and Klinkesorn, 2014).

Proteins as natural food-grade polymers were used: (1) alone and (2) in combination with polysaccharide hydrogel as carrier materials for microencapsulation of many EOs, because of their binding hydrophobic interactions and hydrogen bonding attraction between molecules (Zou et al., 2012; Haratifar and Corredig, 2014; Chuacharoen and Sabliov, 2016). Protein interchain and intrachain self-cross-linking is prerequisite in formation of protein carrier matrix. This crosslinking could be induced in some cases by heat treatment or by changing the pH of a solution (Shpigelman et al., 2010; Tavares et al., 2014). Protein-based carriers, such as gelatin, casein, whey proteins, and soy proteins, have been mostly used for encapsulation of thermosensitive, hydrophobic bioactive compounds (Pool et al., 2013; Xue et al., 2014; Jia et al., 2016). Encapsulation efficiency of these carriers depends on binding affinity of the polyphenols and EOs to protein matrix (Livney, 2010). Release property of bioactive compounds from the protein-based carriers depends on pH conditions. Pronounced swelling of protein-based carriers obtained at neutral pH could induce the undesirable leakage of bioactive compounds (Kimpel and Schmitt, 2015; Liu et al., 2015). Important disadvantage of this type of carriers is significant disintegration under gastric condition caused by pepsin attack (Kumar et al., 2016). Sutaphanit and Chitprasert (2014) used gelatin for microencapsulation of basil EO. Its main components include methyl eugenol (42.58%) followed by caryophyllene (26.88%) and eugenol (10.66%).

Compared to protein-based carriers, combination of protein–polysaccharide carriers can improve mechanical and release properties of the delivery systems and prevent the enzymatic degradation of the proteins in gastric condition (Diaz-Bandera et al., 2013; Jia et al., 2016). In addition, many studies have shown that globular proteins, as well as whey proteins hydrolysates, have antioxidant activity. They can reduce the undesirable oxidation of EOs and provide better oxidative stability of the carriers (Dryakova et al., 2010; Carneiro et al., 2013). The protein–polysaccharide carriers are excellent systems for encapsulation of EOs in order to (1) stabilize these active compounds and (2) protect them from chemical degradation (Turasan et al., 2015; Campelo et al., 2017). Oregano EO emulsion was stabilized by Tween 80 and encapsulated in various types of microcarriers, such as milk powder and whey protein particles, rice starch particles and inulin, and gelatin–sucrose composite (Beirãao da Costa et al., 2012).

Advantage of polysaccharide carriers is in nutrition quality, easy preparation procedure, and low cost. The disadvantage is related to low encapsulation efficiency, loading capacity, and release efficiency in small intestine (de Oliveira et al., 2014). Addition of protein clusters improves their thermal and mechanical stabilities and nutrition quality. The disadvantage of polysaccharide/protein carriers for encapsulation of EOs is also related to low encapsulation efficiency, loading capacity, and release efficiency in small intestine (Dajić Stevanović et al., 2018; Volić et al., 2018).

Lipid-based carriers made by vegetable oils have been widely used for encapsulation of EOs (Bilia et al., 2014). The main advantages of these carriers are (1) good encapsulation efficiency, (2) stability of active compounds under storage conditions and under gastric condition, and (3) thermal stability (Campos et al., 2014). Vegetable oils represent a mixture of triglycerides (major components) and minor components (<5%), such as glycerolipids, such as monoglycerides and diglycerides, phospholipids, and non-glycerolipids, including sterols, tocopherols/tocotrienols, free fatty acids, vitamins, pigments, proteins, phenolic compounds, water, and so on (Yara-Varon et al., 2017).

Other types of lipid-based particles are liposomes and solid lipid carriers. This type of the carriers can be used for encapsulation of hydrophobic, hydrophilic, and amphiphilic molecules (Yoshida et al., 2010). The thin film hydration, freeze–thaw, sonication, and reverse-phase evaporation were mostly used methods for their preparation and encapsulation of EOs. The disadvantages of liposomes are: (1) complex and expensive preparation procedure and (2) reduced stability under storage conditions that could restrict their applications (Akbarzadeh et al., 2013). Solid lipid nanoparticles and nanostructured lipid carriers were used as nanocarriers for the delivering of polyphenol-type catechins (EGCG) (Shi et al., 2013).

Lipid carriers can be combined with proteins in order to improve their chemical and mechanical stabilities, as well as encapsulation efficiency. Carriers made by mixing of proteins and lipid components (β-lactoglobulin-medium chain triglyceride) have been successfully used for the encapsulation of polyphenols (Pool et al., 2013).

Advantages of lipid carriers are higher encapsulation efficiency, loading capacity, and release efficiency in small intestine in comparison with polysaccharide/protein carriers. However, the disadvantage is related to low mechanical and thermal stabilities, which significantly reduce their usefulness, as well as complex preparation procedure, and higher cost in comparison with polysaccharide/protein carriers (Akbarzadeh et al., 2013).

Examples of combined carriers for encapsulation of EOs are provided in Table 3, whereas main challenges in choice of carrier systems for EO encapsulation are illustrated in Figure 4.

Chemical stability of carrier matrices under gastric condition is considered at molecular level and supramolecular level in order to improve their resistance to the attack of pepsin. Affinity and activity of pepsin to the various components of carrier's matrix, such as polysaccharides and proteins under gastric condition, are considered at molecular level in the context of various physical and chemical factors. The structural changes of carrier's matrix represent the cumulative effects of pepsin interactions with the carrier's components and could lead to undesirable carrier weakening and the leakage of active compounds. Deeper understanding of these structural changes is necessary in order to improve the carrier's performances.

Pepsin is the one of the aspartic protease enzymes. All members of this class of enzymes have two aspartic acid residues within their structure that act as the active site. Pepsin could not form chemical bonds with biopolymers. The mechanism of pepsin action is related to the ability of the two aspartic acids at the reaction site to simultaneously act as both an acid and a base.

Affinity and activity of pepsin to biopolymers, such as polysaccharides and proteins under gastric conditions depend on chemical and physical factors. The physical factors of biopolymers are (1) isoelectric point; (2) the surface activity of biopolymer; (3) the flexibility of chains; (4) the conformation of chains under gastric condition, which is related to its hydrophobic/hydrophilic behavior; and (5) chain length. Chemical factors are related to (1) possible pepsin attack to biopolymers and (2) possible pepsin inactivation caused by the presence of biopolymers. Pepsin attack is directed to glycoside bonds (characteristic for polysaccharides) and the peptide bonds of aromatic amino acids, such as tryptophan, tyrosine, phenylalanine, and glutamate (characteristic for proteins). Pepsin inactivation is induced primarily by carboxyl groups and hydroxyl groups of biopolymers.

Polysaccharides rich by carboxyl groups, such as alginate, maltodextrin, and pectin, can inactivate pepsin (Strugala et al., 2005). At the same time, pepsin can hydrolyze these polysaccharide chains. The efficiency of hydrolyze depends on (1) the number of glycoside bonds, which correlates with chain length, (2) the flexibility of chains, and (3) branching of polysaccharide chains. Mannuronic acid is more flexible and more reactive with pepsin than guluronic acid (Chater et al., 2015). Polysaccharides, such as xanthan gum have rigid rod-like chains, which are more resistant to pepsin attack. Branched polysaccharides, such as maltodextrin are more resistant to pepsin attack than unbranched polysaccharide, such as alginate. Pepsin–polysaccharide interactions depend on the charge of polysaccharide under gastric conditions. Interactions between pepsin and polysaccharide molecules are more intensive for molecules with lower value of the isoelectric point. The isoelectric point of (1) xanthan gum is 2.8 (Souza et al., 2013), (2) α-l-gluronic acid is 3.65, (3) β-d-mannuronic acid is 3.38 (Draget et al., 1996), and (4) chitosan is 5.14 (Kalliola et al., 2017). Consequently, short-chain chitosan is more resistant to pepsin attack than alginate because of the higher value of isoelectric point (Boeris et al., 2011). Short chains correspond to lower amount of glycoside bonds per chain, which is desirable.

Efficiency of pepsin attack to proteins depends on (1) their hydrophilic-to-hydrophobic ratio, (2) isoelectric point, (3) the conformation of chains, and (4) interrelation between the mentioned factors under gastric condition. More open conformations enable pepsin attack to aromatic amino acids. β-Lactoglobulin, the major constituent of whey protein, is resistant to pepsin attack in its native form because of its close conformation and low hydrophilic-to-hydrophobic ratio (Lorieau et al., 2018). Contrary, casein and soybean proteins are more reactive with pepsin (Cui et al., 2013; Lorieau et al., 2018).

Lipid carriers represent the best choice in order to keep entrapped active compounds out from the attack of pepsin. Vegetable oils are suitable for the entrapment of EOs, whereas liposomes could be used for immobilization of both hydrophilic and hydrophobic active compounds. Vegetable oils rich by long-chain triglycerides, such as corn oil, nut oil, and canola oil are more suitable because of small digestion rate and resistance to pepsin attack (Majeed et al., 2015).

Polysaccharide hydrogels and polysaccharide–protein composites in the form of microbeads have been widely used for the entrapment of hydrophilic compounds, whereas polysaccharide–protein microbeads have been used for the entrapment of hydrophobic compounds. It is in accordance with the advantage of these carriers, such as (1) easy and cheap preparation procedure and (2) stability under storage conditions in dry state. Ca–alginate have been frequently used for various applications compared with other polysaccharide hydrogels. However, pepsin can easily diffuse through porous structure of amorphous hydrogels and disintegrate them. Hydrodynamic radius of pepsin is 3 nm (Gtari et al., 2017), whereas the average pore size of ionic polysaccharide hydrogel, such as Ca–alginate is in the range from 10 to 20 nm (Funueanu et al., 1999). Diffusion time corresponds to the minute time scale. Grunwald (1989) reported that the internal diffusion of small molecules, such as glucose within 2% Ca–alginate beads was equilibrated during 3 min for a corresponding bead radius of 1.53 mm and during 8 min for corresponding bead radius of 3.20 mm at room temperature.

The process of hydrogel disintegration is much faster than the process of pepsin inactivation by alginate chains. Pepsin inactivation by alginate chains corresponds to the several tens of minutes to hours' time scale (Koutina et al., 2018). The process of hydrogel disintegration corresponds to the diffusion time. In order to improve its stability under gastric condition, Ca–alginate beads have been coated by low-viscosity chitosan (Huguet and Dellacherie, 1996). This is an efficient way to keep hydrophilic active compounds under gastric condition and ensure their transport to low intestine. The blending of Ca–alginate with whey proteins (Zhang S. et al., 2014) improves carriers' resistance to pepsin under gastric condition. Polysaccharide–protein hydrogel carriers consist of (1) polysaccharide phase, which represents the continuum, and (2) dispersed phase, which consists of partially connected protein clusters. Interactions between proteins and polysaccharides at the interface are primarily electrostatic repulsive. The mechanical behavior of these carriers could be understood in the context of two opposite tendencies. Protein clusters are stiffer than surrounding polysaccharide hydrogel. It could be expected that protein addition induces the reinforcement of the carriers. However, both of them are positively charged under gastric condition. Electrostatic repulsive interactions between polysaccharide and protein chains at the interface could induce the weakening of the beads, depending on polysaccharide-to-protein mass ratio.

In summary, most polymeric and oligomeric wrapping structures serving as EOs carriers, such as proteins and carbohydrates, break down by acidic conditions of the gastric phase (Wood, 2005). Digestion rate is directly dependent on the droplet size (Salvia-Trujillo and McClements, 2016), but adversely related to viscosity of dispersion (Ahmad et al., 2018).

Some materials are resistant to gastric digestion (e.g., cellulose and cellulose derivates, resistant starch, some pectins and alginates, etc.) and serve for release of active compounds in the colon, being exposed to subsequent microbial degradation (Belali et al., 2019). Many reports stressed that gut microbial transformation could potentially improve the therapeutic effects of plant bioactive products, including EOs and particular terpenoids (Wang et al., 2019).

In general, the choice of appropriate carrier system and encapsulation technology should be dependent on (1) active ingredient/carrier interaction, (2) bioavailability of the both internal (the active) and the external phase (shell material), (3) release and bioactivity of the active phase at the target site, (4) application needs (e.g., medicine, food, agriculture), (5) safety issues (related to administration route), and (6) sustainability of the entire encapsulation process and economy-based aspects.

Apart from entrapment of EOs for target drug delivery, there is wide current application and further possibility for their use in agriculture and the food and textile industry. Upon recent information, the encapsulated EOs and their individual constituents are used in agriculture, mostly as natural pesticides (e.g., Bakry et al., 2016; Kumar et al., 2019) and phytogenic feed additives (e.g., Dajić Stevanović et al., 2018), because of their antibacterial, antifungal, and insecticidal effects. Because of strong antimicrobial activity and expressed fragrance, encapsulated EOs are used in home textiles and personal care products, as well as in production of functional and fragrant textile products (e.g., Bakry et al., 2016).

The application of encapsulated EOs and their constituents is in evident expansion in industry of functional foods and beverages (e.g., Gomez-Mascaraque et al., 2015; Ye et al., 2018; Dima et al., 2020), natural food preservatives and additives (Stratulat et al., 2014; Bakry et al., 2016), and in production of active food packaging as incorporation of these active additives in polymer matrices results in extended food shelf life (Ribeiro-Santos et al., 2017).

There are many-fold benefits of encapsulated EO products application in biomedicine, cosmetics, agriculture, and food and textile industry, referring to enhanced functionality and bioctivity, prolonged shelf life, improved sensory characteristics, increase of systemic activity, and novelty and innovations. However, the main challenges in wider application of such products are the following: safety and regulation issues, achievement of stability and solubility of the active compound, its integration and interfering with other components of a product, possible development of multicapsulation systems for better performances, and the industrial scale-up and high production costs. Finally, there is a need for implementation of green and sustainable technologies in fabrication of encapsulated products.