Cyclodextrin
Cyclodextrins are a family of cyclic
Cyclodextrins are composed of 5 or more α-D-glucopyranoside units linked 1->4, as in amylose (a fragment of starch). Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape:
- α (alpha)-cyclodextrin: 6 glucose subunits
- β (beta)-cyclodextrin: 7 glucose subunits
- γ (gamma)-cyclodextrin: 8 glucose subunits
The largest well-characterized cyclodextrin contains 32 1,4-anhydroglucopyranoside units. Poorly-characterized mixtures, containing at least 150-membered cyclic oligosaccharides are also known.
Applications
Drug delivery
Cyclodextrins are ingredients in more than 30 different approved medicines.[2] With a hydrophobic interior and hydrophilic exterior, cyclodextrins form complexes with hydrophobic compounds. Alpha-, beta-, and gamma-cyclodextrin are all generally recognized as safe by the U.S. FDA.[3][4] They have been applied for delivery of a variety of drugs, including hydrocortisone, prostaglandin, nitroglycerin, itraconazole, chloramphenicol. The cyclodextrin confers solubility and stability to these drugs.[1] The inclusion compounds of cyclodextrins with hydrophobic molecules are able to penetrate body tissues, these can be used to release biologically active compounds under specific conditions.[5] In most cases the mechanism of controlled degradation of such complexes is based on pH change of water solutions, leading to the loss of hydrogen or ionic bonds between the host and the guest molecules. Alternative means for the disruption of the complexes take advantage of heating or action of enzymes able to cleave α-1,4 linkages between glucose monomers. Cyclodextrins were also shown to enhance mucosal penetration of drugs.[6]
Chromatography
β-cyclodextrins are used to produce
Other
Cyclodextrins bind
Cyclodextrins are also used to produce alcohol powder by encapsulating ethanol. The powder produces an alcoholic beverage when mixed with water, or can also be taken in a pill.[8] The approval of powdered alcohol by the FDA in 2014 was met with wide-spread bans and backlash in the United States.[9]
Structure
Typical cyclodextrins are constituted by 6-8 glucopyranoside units. These subunits are linked by 1,4
Synthesis
Cyclodextrins are prepared by enzymatic treatment of
Derivatives
Interest in cyclodextrins is enhanced because their host–guest behavior can be manipulated by chemical modification of the hydroxyl groups. O-
Both β-cyclodextrin and methyl-β-cyclodextrin (MβCD) remove
Due to the covalent attachment of thiol groups to cyclodextrins high mucoadhesive properties can be introduced as these thiolated oligomers (thiomers) are capable of forming disulfide bonds with cysteine-rich subdomains of mucus glycoproteins. The gastrointestinal and ocular residence time of thiolated cyclodextrins is therefore substantially prolonged.[16][17] Furthermore, thiolated cyclodextrins are actively taken up by target cells releasing their payload into the cytoplasma. The cellular uptake of various model drugs, for instance, was up to 20-fold improved by using thiolated α-cyclodextrin as carrier system.[18]
Research
In
β-Cyclodextrin complexes with certain carotenoid food colorants have been shown to intensify color, increase water solubility and improve light stability.[20][21]
Complexes formed between β-cyclodextrin and adamantane derivatives have been used to make self-healing materials, such as hydrogels[22] and low-friction surfaces.[23]
History
Cyclodextrins were called "cellulosine" when first described by A. Villiers in 1891.[24] Soon after, F. Schardinger identified the three naturally occurring cyclodextrins: α, β, and γ, referred to as "Schardinger sugars". For 25 years, between 1911 and 1935, Hans Pringsheim in Germany was the leading researcher in this area,[25] demonstrating that cyclodextrins formed stable aqueous complexes with many other chemicals. By the mid-1970s, each of the natural cyclodextrins had been structurally and chemically characterized and many more complexes had been studied. Since the 1970s, extensive work has been conducted by Szejtli and others exploring encapsulation by cyclodextrins and their derivatives for industrial and pharmacologic applications.[26] Among the processes used for complexation, the kneading process seems to be one of the best.[27]
Safety
Cyclodextrins are of wide interest in part because they appear nontoxic in animal studies. The
References
- ^ ISBN 978-3527306732.
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- ^ GRAS Notice No. GRN 000155, alpha-cyclodextrin;GRAS Notice No. GRN 000074, beta-cyclodextrin;GRAS Notice No. GRN 000046, gamma-cyclodextrin
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- ^ "Powdered Alcohol: An Encapsulation | National Alcohol Beverage Control Association". www.nabca.org. Retrieved 2024-01-22.
- ^ "Powdered Alcohol". Alcohol.org. Retrieved 2024-01-22.
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- ^ Villiers A. "Sur la transformation de la fécule en dextrine par le ferment butyrique". Compt. Rend. Acad. Sci. 1891: 536–8.
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