Cyclodextrin
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by
Cyclodextrins are composed of 5 or more
α (alpha)-cyclodextrin: 6 glucose subunitsβ (beta)-cyclodextrin: 7 glucose subunitsγ (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
[edit]Drug delivery
[edit]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
Chromatography
[edit]Other
[edit]Cyclodextrins bind fragrances. Such devices are capable of releasing fragrances when heated, such as by ironing, body heat, or a dryer. A common application is a typical 'dryer sheet'. They are also the main ingredient in Febreze, which claims that the
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
[edit]Typical cyclodextrins are constituted by 6-8 glucopyranoside units. These subunits are linked by 1,4 glycosidic bonds. The cyclodextrins have toroidal shapes, with the larger and the smaller openings of the toroid exposing to the solvent secondary and primary hydroxyl groups respectively. Because of this arrangement, the interior of the toroids is considerably less hydrophilic than the aqueous environment and thus able to host hydrophobic molecules. In contrast, the exterior is sufficiently hydrophilic to impart cyclodextrins (or their complexes) water solubility. They are not soluble in typical organic solvents.
Synthesis
[edit]Cyclodextrins are prepared by enzymatic treatment of starch.[10][11] Commonly cyclodextrin glycosyltransferase (CGTase) is employed along with
Derivatives
[edit]Interest in cyclodextrins is enhanced because their host–guest behavior can be manipulated by chemical modification of the hydroxyl groups. O-Methylation and acetylation are typical conversions. Propylene oxide gives hydroxypropylated derivatives.[1] The primary alcohols can be tosylated. The degree of derivatization is an adjustable, i.e. full methylation vs partial.[14]
Both
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
Research
[edit]In supramolecular chemistry, cyclodextrins are precursors to mechanically interlocked molecular architectures, such as rotaxanes and catenanes. Illustrative,
Complexes formed between
Using the host-guest interaction between
History
[edit]Cyclodextrins were called "cellulosine" when first described by A. Villiers in 1891.[27] Soon after, F. Schardinger identified the three naturally occurring cyclodextrins:
Safety
[edit]Cyclodextrins are of wide interest in part because they appear nontoxic in animal studies. The LD50 (oral, rats) is on the order of grams per kilogram.[1]
Nevertheless, attempts to use
References
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