**4. Cyclodextrins**

Cyclodextrin had its origin around 1981, when Villier discovered a new starch derivative obtained from bacterial degradation, which presented properties similar to those of cellulose, and distinguished two types of crystals of cellulosin: the cyclodextrins α and β [95]. Twelve years later, when studying the bacterial digestion of starch, Szejtli [95] identified two crystalline products with the same characteristics as Villier's cellulosins. Deepening his studies, he perfected the process of obtaining these crystals and isolated the bacterium that produced them, deeming it *Bacillus macerans*. The crystalline products were called crystallized α-dextrin and β-dextrin. Later, λ-dextrin was also isolated, and several fractionation schemes for the production of cyclodextrins were developed [96].

Cyclodextrins (CD's) are cyclic oligosaccharides consisting of glucose units linked by α-(1,4) glycosidic bonds derived from the enzymatic degradation of starch by certain bacteria, and they are chemically and physically stable molecules [95, 97]. The most common natural CDs have six, seven, and eight d-glucopyranose units and are named α, β, and γ cyclodextrin, respectively, and they differ from each other by virtue of ring size and solubility [98]. While the central cavity of CDs has a hydrophobic character, the surrounding walls are hydrophilic, and this feature allows CDs to form capsules, acting as a host for lipophilic compounds in their cavities and forming inclusion complexes [97, 99–101].

The binding of bioactive compounds within the host cyclodextrin is not fixed or permanent, but rather a dynamic equilibrium. This way, the formation of inclusion complexes is result of an equilibrium between the free and CD molecules and the bioactive compounds—CD complex [99]. Therefore, some factors may affect inclusion complex formation, such as type of cyclodextrin, cavity size, pH and ionization state, temperature, and method of preparation [102].

CD molecules are cone-like in shape with a cavity 7.9 Å deep. The upper and lower diameters of the CD wells are 4.7 and 5.3 Å, 6.0 and 6.5 Å, and 7.5 and 8.3 Å for α-CD, β-CD, and γ-CD, respectively [45].

Marques [102] notes that the goal of encapsulation using cyclodextrin is to reduce the volatility and toxicity of the encapsulated compounds, provide protection of compounds that are sensitive to factors that promote their degradation, and alter the kinetics of migration and

**α-CD β-CD γ-CD**

β-Cyclodextrins as Encapsulating Agents of Essential Oils http://dx.doi.org/10.5772/intechopen.73568 181

14.2 1.85 23.2

The use of cyclodextrins is verified in diverse industrial products, such as pharmaceuticals [107, 111, 112], agrochemicals [113–115], and foods [116–119]. In the food area, cyclodextrins are nontoxic and considered GRAS, and thus are used for several purposes [120, 121]. These structures offer increased resistance to degradation of the active compounds and make the

Szente and Szejtli [104] studied the toxicity of CDs and demonstrated that oral administration of high doses of CDs does not cause any harm. Several studies have shown that CDs are nontoxic and do not present intoxication risks, because they are not absorbed in the gastrointestinal tract or through lipophilic biological membranes, and the same results have been obtained with regard to teratogenicity and mutagenicity [124–128]. Antisperger [129] also evaluated the toxicity of CDs when introduced in an amount equivalent to 20% in the diet of

The thermal degradation is one of the main natural compounds' degradation forms. In most cases, the increase in temperature is undesirable, as it favors the volatilization of less stable compounds, which are responsible for the biological activity. Therefore, the thermal degradation makes it impossible to apply many of the natural compounds studied, due to the

release of the encapsulated active components into the external environment.

Glucose number 6 7 8 Molecular mass 972 1135 1297

Cavity diameter (Â) 4.7–5.3 6.0–6.5 1.5–8.3

Pk 12.332 12.202 12.081 Melting point (°C) 275 280 275 Surface tension (nM/m) 73 73 73 Rate of acid hydrolysis (h−1) 0.11 0.13 0.23

) 174 262 427 Crystal form Hexagonal blades Monoclinic parallelograms Quadratic prisms

host-microcapsule complex more stable [53, 56, 57, 122, 123].

**Table 1.** Physical and chemical properties of α-CD, β-CD, and γ-CD.

rats and dogs and found no toxicity.

Aqueous solution (g 100 mL−1

at 25°C)

Cavity volume (Â<sup>3</sup>

Source: [95].

**5. Cyclodextrins in thermal protection**

Among the CDs, β-CD is the most used, because its apolar cavity can host molecules of molecular masses between 100 and 400 g mol−1, which is the molecular mass range of most molecules of interest. β-CD is also easy to recover industrially through the crystallization process [103], and it has the lowest solubility and an intermediate size (**Table 1**). In addition, β-CD production is the most economically viable, with an industrial cost per kilogram approximately 20 times lower than that of the other CD types [104].

These inclusion complexes are important because they improve the chemical and physical stability and solubility of the compounds encapsulated in water. Due to the solubility of CDs in water and because they have the ability to form reversible inclusion complexes with nonpolar molecules in aqueous solution, the water molecules inside the ring are easily replaced by non-polar molecules or molecules with less polarity than water, forming structures that are energetically more stable [105].

The encapsulation can reduce volatilization rates, and promote the gradual release of the encapsulated molecules, which improves their efficacy and bioavailability. Furthermore, they act as protectors against oxidative damage, light degradation, and heat, and other adverse effects linked to the medium in which they are inserted and maintain the initial characteristics of the compound for a long period. These inclusion complexes are relatively more hydrophilic and larger in size than the non-associated active compound, which helps to increase the retention of the encapsulated substance. They are also very interesting because they can mask undesirable flavors and odors that the encapsulated compounds may present [21, 56, 72, 101, 102, 106–110].


**Table 1.** Physical and chemical properties of α-CD, β-CD, and γ-CD.

years later, when studying the bacterial digestion of starch, Szejtli [95] identified two crystalline products with the same characteristics as Villier's cellulosins. Deepening his studies, he perfected the process of obtaining these crystals and isolated the bacterium that produced them, deeming it *Bacillus macerans*. The crystalline products were called crystallized α-dextrin and β-dextrin. Later, λ-dextrin was also isolated, and several fractionation schemes for the produc-

Cyclodextrins (CD's) are cyclic oligosaccharides consisting of glucose units linked by α-(1,4) glycosidic bonds derived from the enzymatic degradation of starch by certain bacteria, and they are chemically and physically stable molecules [95, 97]. The most common natural CDs have six, seven, and eight d-glucopyranose units and are named α, β, and γ cyclodextrin, respectively, and they differ from each other by virtue of ring size and solubility [98]. While the central cavity of CDs has a hydrophobic character, the surrounding walls are hydrophilic, and this feature allows CDs to form capsules, acting as a host for lipophilic compounds in

The binding of bioactive compounds within the host cyclodextrin is not fixed or permanent, but rather a dynamic equilibrium. This way, the formation of inclusion complexes is result of an equilibrium between the free and CD molecules and the bioactive compounds—CD complex [99]. Therefore, some factors may affect inclusion complex formation, such as type of cyclodextrin, cavity size, pH and ionization state, temperature, and method of preparation [102].

CD molecules are cone-like in shape with a cavity 7.9 Å deep. The upper and lower diameters of the CD wells are 4.7 and 5.3 Å, 6.0 and 6.5 Å, and 7.5 and 8.3 Å for α-CD, β-CD, and γ-CD,

Among the CDs, β-CD is the most used, because its apolar cavity can host molecules of molecular masses between 100 and 400 g mol−1, which is the molecular mass range of most molecules of interest. β-CD is also easy to recover industrially through the crystallization process [103], and it has the lowest solubility and an intermediate size (**Table 1**). In addition, β-CD production is the most economically viable, with an industrial cost per kilogram approxi-

These inclusion complexes are important because they improve the chemical and physical stability and solubility of the compounds encapsulated in water. Due to the solubility of CDs in water and because they have the ability to form reversible inclusion complexes with nonpolar molecules in aqueous solution, the water molecules inside the ring are easily replaced by non-polar molecules or molecules with less polarity than water, forming structures that are

The encapsulation can reduce volatilization rates, and promote the gradual release of the encapsulated molecules, which improves their efficacy and bioavailability. Furthermore, they act as protectors against oxidative damage, light degradation, and heat, and other adverse effects linked to the medium in which they are inserted and maintain the initial characteristics of the compound for a long period. These inclusion complexes are relatively more hydrophilic and larger in size than the non-associated active compound, which helps to increase the retention of the encapsulated substance. They are also very interesting because they can mask undesirable flavors and odors that the encapsulated compounds may present [21, 56, 72, 101, 102, 106–110].

tion of cyclodextrins were developed [96].

180 Cyclodextrin - A Versatile Ingredient

respectively [45].

energetically more stable [105].

their cavities and forming inclusion complexes [97, 99–101].

mately 20 times lower than that of the other CD types [104].

Marques [102] notes that the goal of encapsulation using cyclodextrin is to reduce the volatility and toxicity of the encapsulated compounds, provide protection of compounds that are sensitive to factors that promote their degradation, and alter the kinetics of migration and release of the encapsulated active components into the external environment.

The use of cyclodextrins is verified in diverse industrial products, such as pharmaceuticals [107, 111, 112], agrochemicals [113–115], and foods [116–119]. In the food area, cyclodextrins are nontoxic and considered GRAS, and thus are used for several purposes [120, 121]. These structures offer increased resistance to degradation of the active compounds and make the host-microcapsule complex more stable [53, 56, 57, 122, 123].

Szente and Szejtli [104] studied the toxicity of CDs and demonstrated that oral administration of high doses of CDs does not cause any harm. Several studies have shown that CDs are nontoxic and do not present intoxication risks, because they are not absorbed in the gastrointestinal tract or through lipophilic biological membranes, and the same results have been obtained with regard to teratogenicity and mutagenicity [124–128]. Antisperger [129] also evaluated the toxicity of CDs when introduced in an amount equivalent to 20% in the diet of rats and dogs and found no toxicity.
