PRODUCTS

CYCLODEXTRIN

Cyclodextrins (CDs/ CD) = Celdex

Cas no: 12619-70-4

Cyclodextrins are composed of 5 or more α-D-glucopyranoside units linked 1->4, as in amylose (a fragment of starch).
The largest cyclodextrin contains 32 1,4-anhydroglucopyranoside units, while as a poorly characterized mixture, at least 150-membered cyclic oligosaccharides are also known.
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

Cyclodextrins are ingredients in more than 30 different approved medicines.
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.
They have been applied for delivery of a variety of drugs, including hydrocortisone, prostaglandin, nitroglycerin, itraconazol, chloramphenicol.
The cyclodextrin confers solubility and stability to these drugs.
Cyclodextrin 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.
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.

Chromatography
β-cyclodextrins are used to produce stationary phase media for HPLC separations.

Other
Cyclodextrins bind fragrances. Such devices are capable of releasing fragrances during ironing or when heated by human body.
Such a device commonly used is a typical 'dryer sheet'.
The heat from a clothes dryer releases the fragrance into the clothing.
They are the main ingredient in Febreze which claims that the β-cyclodextrins "trap" odor causing compounds, thereby reducing the odor.

Cyclodextrins are also used to produce alcohol powder by encapsulating ethanol. The powder produces an alcoholic beverage when mixed with water.

Structure
γ-CD toroid structure showing spatial arrangement.
Typical cyclodextrins are constituted by 6-8 glucopyranoside units.
These subunits are linked by 1,4 glycosidic bonds.
Cyclodextrins 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 not hydrophobic, but considerably less hydrophilic than the aqueous environment and thus able to host other 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
Cyclodextrins are prepared by enzymatic treatment of starch.
Commonly cyclodextrin glycosyltransferase (CGTase) is employed along with α-amylase.
First starch is liquified either by heat treatment or using α-amylase, then CGTase is added for the enzymatic conversion.
CGTases produce mixtures of cyclodextrins, thus the product of the conversion results in a mixture of the three main types of cyclic molecules, in ratios that are strictly dependent on the enzyme used: each CGTase has its own characteristic α:β:γ synthesis ratio.
Purification of the three types of cyclodextrins takes advantage of the different water solubility of the molecules: β-CD which is poorly water-soluble (at 25C) can be easily retrieved through crystallization while the more soluble α- and γ-CDs (145 and 232 g/l respectively) are usually purified by means of expensive and time consuming chromatography techniques.
As an alternative a "complexing agent" can be added during the enzymatic conversion step: such agents (usually organic solvents like toluene, acetone or ethanol) form a complex with the desired cyclodextrin which subsequently precipitates.
The complex formation drives the conversion of starch towards the synthesis of the precipitated cyclodextrin, thus enriching its content in the final mixture of products.
Wacker Chemie AG uses dedicated enzymes, that can produce alpha-, beta- or gamma-cyclodextrin specifically.
Cyclodextrin is very valuable especially for the food industry, as only alpha- and gamma-cyclodextrin can be consumed without a daily intake limit.
Crystal structure of a rotaxane with an α-cyclodextrin macrocycle.

Derivatives
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.
Cyclodextrin primary alcohols can be tosylated.
Cyclodextrin degree of derivatization is an adjustable, i.e. full methylation vs partial.

Both β-cyclodextrin and methyl-β-cyclodextrin (MβCD) remove cholesterol from cultured cells.
Cyclodextrin methylated form MβCD was found to be more efficient than β-cyclodextrin.
Cyclodextrin water-soluble MβCD is known to form soluble inclusion complexes with cholesterol, thereby enhancing its solubility in aqueous solution.
MβCD is employed for the preparation of cholesterol-free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside cyclodextrin rings.
MβCD is also employed in research to disrupt lipid rafts by removing cholesterol from membranes.
Research
In supramolecular chemistry, cyclodextrins are precursors to mechanically interlocked molecular architectures, such as rotaxanes and catenanes.
Illustrative, α-cyclodextrin form second-sphere coordination complex with tetrabromoaurate anion.

Beta-cyclodextrin complexes with certain carotenoid food colorants have been shown to intensify color, increase water solubility and improve light stability.

History
Space filling model of β-cyclodextrin.
Cyclodextrins, as they are known today, were called "cellulosine" when first described by A. Villiers in 1891.
Soon after, F. Schardinger identified the three naturally occurring cyclodextrins -α, -β, and -γ.
These compounds were therefore referred to as "Schardinger sugars".
For 25 years, between 1911 and 1935, Pringsheim in Germany was the leading researcher in this area, 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.
Among the processes used for complexation, the kneading process seems to be one of the best.

Safety
Cyclodextrins are of wide interest in part because they are nontoxic.
The LD50 (oral, rats) is on the order of grams per kilogram.
Nevertheless, attempts to use β-Cyclodextrin for the prevention of atherosclerosis,age-related lipofuscin accumulation and obesity encounter an obstacle in the form of damage to the auditory nerve and nephrotoxic effect.

Cyclodextrins are a family of cyclic oligosaccharides with widespread usage in medicine, industry and basic sciences owing to their ability to solubilize and stabilize guest compounds.
In medicine, cyclodextrins primarily act as a complexing vehicle and consequently serve as powerful drug delivery agents.
Recently, uncomplexed cyclodextrins have emerged as potent therapeutic compounds in their own right, based on their ability to sequester and mobilize cellular lipids. Cyclodextrin particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD) has garnered attention because of its cholesterol chelating properties, which appear to treat a rare neurodegenerative disorder and to promote atherosclerosis regression related to stroke and heart disease.

Introduction
Ototoxicity in the form of iatrogenic hearing loss arising from various pharmacological treatments has been well-described for more than 1000 years.
Cyclodextrin these cases, drug treatments, often administered for life-threatening diseases, bring to bear a dilemma balancing the risk to hearing with the desire to remedy disease.
Recently, a new class of ototoxic compounds was identified—cyclodextrins.
Though these compounds have many roles in industrial and medicinal applications as solvents and stabilizers, the risk to hearing only became apparent when highly concentrated doses of cyclodextrin were being evaluated as a treatment for the devastating neurological disorder, Niemann-Pick Disease Type C (NPC).
Cyclodextrin this review article, we summarize the nature of these compounds, the evidence of cyclodextrin-induced hearing loss in human patients and animal models, and speculate about potential mechanisms that may underlie this ototoxicity.

Cyclodextrin Types and Structure
Cyclodextrins are ring-shaped oligosaccharides formed in nature by the digestion of cellulose by bacteria.
They are composed of varying numbers of glucose units held together by α-1, 4 glycosidic bonds.
The naturally occurring varieties contain at least six glucose units, with the most common having six, seven, or eight (so called, α-, β-, and γ- cyclodextrins, respectively).
Cyclodextrins with more than eight glucose members are less common in nature and less well characterized, and compounds with five glucose units are only synthetic. Bountiful research has been poured into α-, β-, and γ- cyclodextrins and their properties are well characterized.
Cyclodextrin ring these molecules form is often depicted as a cup-shaped toroid.
Cyclodextrin outside of the cup is hydrophilic, and the inside is more hydrophobic.
Thus, these chemicals are water soluble with the ability to contain hydrophobic guest molecules within them, singly or as dimers.
Cyclodextrin resulting increase in solubility and stability of the guest compounds is the predominant basis for the vast medical, industrial and scientific uses of cyclodextrins.
Much effort has been expended on improving and tailoring this characteristic by chemical substitution of the hydrogen in the hydroxyl groups, which form the mouths of the toroidal openings, extending from the glucose units.
Some common substitutions at these sites are methyl, hydroxylpropyl and sulfobutylether groups.
Adding these groups occurs with different efficiencies and results in different sets of impurities along with the intended reaction product.
Cyclodextrin is chemically difficult to achieve substitution of all possible sites, so a reaction process results in a “degree of substitution”, often expressed as the average number of substituted groups present per molecule or per glucose unit.
Different processes produce varied degrees of substitution, and this can have advantages, since both the nature of the substituent group and the degree of substitution influence the performance of the cyclodextrin in ways that can be useful.

Abstract
Cyclodextrins (CDs) are cyclic oligomers of d-(+)-glucopyranose units linked through α-1,4-glycoside bonding.
CDs are produced from starch, not from fossil resources, and are practically nontoxic.
CDs recognize hydrophobic guest compounds, of which shape and size match the cavity, to form inclusion complexes in aqueous media.
CDs have thus been widely used in industry and academia as functional compounds with molecular recognition ability.
This entry overviews CDs; the historical background, basic characteristics and inclusion behavior, industrial applications, and cutting-edge applications.

Cyclodextrins
CDs are a family of the classical cyclic oligosaccharides formed during bacterial digestion of cellulose, and were discovered in 1891 by Villiers.
These cyclic oligosaccharides consist of (α-1,4)-linked α-d-glucopyranose units and contain a significantly hydrophobic central cavity and a hydrophilic outer surface.
Because of the chair conformation of the glucopyranose units, the CDs are shaped like a truncated cone.
Cyclodextrin central cavity is lined by the skeletal carbons and ethereal oxygens of the glucose residues, which gives it a hydrophobic character and is instrumental for binding nonpolar alkyl and aryl residues.
Cyclodextrin polarity of the cavity has been estimated to be similar to that of ethanol solution.
Cyclodextrin hydroxyl functions are orientated to the cone exterior, with the primary hydroxyl groups of the sugar residues at the narrow edge of the cone and the secondary hydroxyl groups at the wider edge.
This arrangement provides additional hydrogen bonding sites for the binding of organic guests, particularly anionic guest molecules.
Cyclodextrin natural α-, β- and γ-CDs consist of six, seven, and eight glucopyranose units, respectively.
CDs are the first receptor molecules whose binding properties toward organic molecules have been recognized and extensively investigated, yielding a wealth of results concerning physical and chemical features of molecular complexation.
The binding constants of CD-based host–guest complexes range typically from 10 to 105 M− 1,18,19 which requires millimolar concentrations of the macrocycle to achieve a significant complexation of the guest molecules in aqueous solution.
Although the natural CDs and their complexes are hydrophilic, their aqueous solubility is rather limited, especially that of β-CD (16 mM).
Cyclodextrin imposes limitations on the extensive uses of CD-based host–guest systems in various applications as quantitative complexation is often difficult to achieve with submillimolar concentrations of guests.
Cyclodextrin is, however, important to mention that the hydrophilic CDs are nontoxic at low to moderate oral dosages and they have immense prospects in medicinal use, especially in drug formulation.

Cyclodextrins were discovered in the late 19th century; beautiful crystals were observed from a starch digest of Bacillus amylobacter having the chemical composition represented.
Bacillus macerans contamination produced the cyclodextrins with impure bacterial cultures.
In 1903, Schardinger isolated crystalline products such as dextrins A and B and reported their lack of minimizing power.

In 1904, Schardinger used starch and sugar-containing plant material to isolate a new organism which can produce alcohol derivatives.
In 1911, he named Bacillus macerans to the strain, which is responsible for producing significant amounts of crystalline dextrins from starch.
Schardinger has given a name to his crystalline product, that is, crystallized dextrin α and dextrin β.
In 1935, before isolation of γ dextrin, different fractionation schemes were developed to produce cyclodextrins.
During this period, the cyclodextrins structures were still unknown, but in 1942, the structures of α-cyclodextrin and β-cyclodextrin were revealed with the use of X-ray crystallography method.
In 1948, it was identified that the unique structure of γ-cyclodextrins could form host-guest inclusion complexes.

Cyclodextrins are composed of primary (C6) and secondary (C2 and C3) hydroxyl groups which were recognized by CDs X-ray structures.
Cyclodextrin primary groups are located on the edge of CDs rings and secondary groups situated on the outer edge of the CDs ring and ether-like oxygen and polar C3 and C5 hydrogen groups inside the CDs torus.
Cyclodextrin outcome of this kind of structure represents the polar cavity inside, which provides lipophilic matrix and hydrophilic outside, which can be dissolved in water, and a ‘micro-heterogeneous environment’.

Chemistry of cyclodextrins
The cyclodextrins (CDs) are produced by enzymatic degradation of sugar and starch.
These are cyclic oligosaccharides comprised of glucose units linked by α-1,4-glycosidic bonds.
Cyclodextrins are available in three forms such as α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, which comprised of six, seven, and eight α-1,4-glycosidic bonds. These are lipophilic from inside which can host the guest molecules such as oils, waxes, and fats.
Cyclodextrin ability to form host-guest complexes is vital for stabilizing and solubilizing hydrophobic compounds in solvents

CDs are chemically and physically stable macromolecules.
They are synthesized by the enzymatic degradation of starch.
Chemically, they are cyclic oligosaccharides consisting of α-1,4-glycosidic bonded d-glycopyranose units.
They belong to the family of cage molecules.
The CDs are categorized based on the number of glucose residues in their structure; for example, a CD with the glucose hexamer is named as α-CD, the heptamer as β-CD, and the octomer as γ-CD.
CD molecules are shaped like a truncated cone or torus with two open ends because of their chair conformation of glucopyranose units.
The glucopyranose units are in 4C1 conformation, where the C stands for the “chair” conformation of the monosaccharide ring and the numbers indicate the location of carbon atoms that are above and below the rest of the carbons.
Due to this conformation, all secondary hydroxyl groups above are on one edge of the ring and the primary hydroxyl group is on the other edge.
Cyclodextrin secondary hydroxyl side opens up slightly more than the primary hydroxyl side, which is why the cavities are “V” shaped.
Cyclodextrin cavity is lined by the hydrogen atoms and the glycosidic oxygen bridges, respectively.
Cyclodextrin nonbonding electron pairs of the glycosidic oxygen bridges are directed toward the inside of the cavity producing a high electron density there and lending to it some Lewis base characteristics

Many metabolically important compounds, such as lipid-soluble vitamins and hormones, have very low solubilities in aqueous solutions.
Various techniques have been used to solubilize these compounds in tissue culture, cell culture, or other water-based applications.
A frequently used approach is to use cyclodextrin as a “carrier” molecule to facilitate the dissolution of these compounds.

The solubility of natural cyclodextrins is very poor and initially this prevented cyclodextrins from becoming effective complexing agents.
In the late 1960’s, it was discovered that chemical substitutions at the 2-, 3-, and 6-hydroxyl sites would greatly increase solubility.
Cyclodextrin degree of chemical substitution and the nature of the groups used for substitution determine the final maximum concentration of cyclodextrin in an aqueous medium.
Most chemically modified cyclodextrins are able to achieve a 50% (w/v) concentration in water.

Cavity size is the major determinant as to which cyclodextrin is used in complexation.
“Fit” is critical to achieving good incorporation of cyclodextrins.
α-Cyclodextrins have small cavities that are not capable of accepting many molecules.
γ-Cyclodextrins have much larger cavities than many molecules to be incorporated, and cyclodextrin hydrophobic charges cannot effectively interact to facilitate complexation.
The cavity diameter of β-cyclodextrins has been found to be the most appropriate size for hormones, vitamins, and other compounds frequently used in tissue and cell culture applications.
For this reason, β-cyclodextrin is most commonly used as a complexing agent.

Hydrophobic molecules are incorporated into the cavity of cyclodextrins by displacing water.
Cyclodextrin reaction is favored by the repulsion of the molecule by water.
Cyclodextrin effectively encapsulates the molecule of interest within the cyclodextrin, rendering the molecule water-soluble.
When the water-soluble complex is diluted in a much larger volume of aqueous solvent, the process is reversed, thereby releasing the molecule of interest into the solution.

Our product line of water-soluble complexes includes cyclodextrins and soluble cyclodextrin-complexes of biochemicals commonly used in tissue and cell culture applications.

Most of the drugs administered through oral route have poor aqueous solubility and dissolution rate.
Cyclodextrin and its derivates represent as pharmaceutical adjuvants to overcome this challenges and helps in development of stable formulation with enhanced bioavailability.
Cyclodextrins are unique structure with versatile physicochemical properties which aids the pharmaceutical scientists to overcome drug delivery challenges for poorly aqueous soluble drugs.
Cyclodextrin and its derivates are widely useful as solubilizers, assisting in preparation of various dosage forms such as liquid oral, solid, and parenteral preparations.
Cyclodextrins interacts with appropriately sized guest molecules to form inclusion complex and enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs.
Through the various reported literatures, the review highlights the concept of cyclodextrin and its derivatives in enhancing solubility and bioavailability of poorly aqueous soluble drugs.

Oral bioavailability of poorly aqueous soluble drugs remains one of the most challenging aspects for researchers in formulation development of dosage forms.
Nearby, 70 % of existing new drug molecules are poorly aqueous soluble and require a suitable candidate for enhancing oral bioavailability and solubility.
Drugs having the water solubility of <10 mg/ml over the pH range of 1-7 at 37°C show bioavailability issues.
According to Biopharmaceutical Classification System (BCS), drugs which are poorly soluble but highly permeable falls under BCS class II category.
These poorly aqueous soluble drug molecules exhibit slow drug absorption leading to poor and erratic bioavailability and finally causes GI mucosal toxicity.
Low solubility, poor dissolution rate and compromised oral absorption are the major problems of BCS Class II drugs and hence enhancing solubility of such actives is a major challenge for the pharmaceutical and academic researchers.

Cyclodextrins (CDs) represents one of the pharmaceutical excipient in overcoming this challenge. CDs are molecules of natural origin, discovered earlier by Villiers in 1891.
Cyclodextrin interest in application of CDs was later on studied by Austrian microbiologist Franz Schardinger in the twentieth century which became the most important topic of interest in pharmaceutical and other fields since from late 1970s to later on.
He described about two crystalline compounds isolated from bacterial digest of potato starch called α-dextrin and β-dextrin which were later and now called as α-CD and β-CD.
Over the span of time, CDs have created a quality platform for various applications like increasing drug solubility and stability, masking odors and tastes,enhancing drug absorption,6 controlling drug release profiles, alleviating local and systemic toxicity, and improving drug permeability across biological barriers.
CDs containing formulations have been delivered through various delivery systems like oral, ocular, nasal, dermal and rectal.
From application point of view, CDs offers various advantages like non-toxic, low cost, safety (recognized by safety health authorities) and easily available.
Various published reports demonstrate wide application of CDs to enhance oral bioavailability of poorly aqueous soluble drugs.

Structure of CDs
CDs are cyclic oligosaccharides obtained from starch degradation by cycloglycosyl transferase amylases produced by various bacilli (Bacillus macerans and B circulans). Depending on the exact reaction conditions, three main types of CDs are obtained, α-, β-, and γ-CD, each comprises six to eight dextrose units respectively.
CDs are ring molecules which lack free rotation at the level of bonds between glucopyranose units, they are not cylindrical rather they are toroidal or cone shaped. CDs consists of hollow tapered cavity consist of 0.79 nm in depth in which the active molecule is incorporated.
The primary hydroxyl groups are located on the narrow side whereas the secondary groups are on the wider side.
The properties of CDs can be modified by substituting different functional groups on the CDs rim.
Substituting the hydroxyl group of CD by chemical and enzymatic reactions by variety of substituting groups like hydroxypropyl-, methyl-, carboxyalkyl-, thio-, tosyl-, amino-, maltosyl-, glucosyl-, and sulfobutyl ether-groups to β-CD can increase the solubility.
Solubility of nonpolar solutes occurs due to the nonpolar nature (lipophilic) of the internal cavity of CDs whereas, the polar nature (hydrophilic) of CDs external part helps in solubilising the CDs and drug in aqueous solution.
Due to this characteristics nature, CDs have attained a great interest as a solubilising candidate and has overcome the biopharmaceutical deficiencies of various drugs in the recent years.
CDs are widely soluble in some polar, aprotic solvents, but insoluble in most organic solvents.
Although, CDs exhibit higher solubility in some of the organic solvents than in water, inclusion complexes do not take place in non-aqueous solvents because of the increased affinity of guest molecule for the solvent compared to its affinity for water.
Strong acids such as hydrochloric acid and sulfuric acid can hydrolyze CDs. This hydrolysis rate depends upon temperature and concentration of the acid. CDs are stable against bases.
Cyclodextrin hydrophobic cavity in CDs can partially accommodate low molecular lipophilic drug molecule and polymers.
Hydrophilic drug-CD complexes are formed by inclusion of lipophilic drug or lipophilic drug molecule in the central cavity.
The lipophilic cavity thus protects the lipophilic guest molecule from aqueous environment, while the outer polar surface of the CD provides the solubilizing effect.

β‒CD derivative in oral delivery
Certain CDs limit its application in pharmaceuticals due to its low solubility and poor safety.
One of them includes β-CD which shows low solubility and produces haemolytic activity and strong irritancy.
However, some β-CD derivatives can overcome these shortcomings.
Nevertheless, owing to its low price β-CD derivatives are widely used in pharmaceutically marketed formulations.
The solubility of β-CD in water is relatively low (approximately 18.5 54 mg/mL at 25 °C), whereas its derivative hydroxypropyl-β-Cyclodextrin has a higher aqueous solubility (approx. 600 55 mg/mL at 25 °C).
Based on published reports, Hydroxypropyl-β-cyclodextrin is widely used derivative of β-CD in improving the solubility of hydrophobic drugs with its better aqueous solubility and higher safety.
Table 1 represents the natural CDs and its available derivatives.
Various reports have been published on β-CD as a host in inclusion complexes with the guest molecules and have been patent.
Inclusion complex involves stoichiometric molecular phenomenon.
CDs as a host forms hydrophilic inclusion complexes (When this cavity is filled with the molecule of another substance, it is called an inclusion complex) with the hydrophobic drug moieties (guest) by incorporating the guest molecule into the internal cavity in the ratio of 1:1 and thereby altering the physicochemical properties of active molecule without any change in the intrinsic properties of active molecule.
Such, changes in the physicochemical properties of the drug molecules such as solubility, dissolution rate, stability and bioavailability contributes CDs as an apt candidate for oral drug delivery in the pharmaceutical field.
Figure 1 depicts the guest-host inclusion complexes formation.
Drug/CD inclusion complexes are usually prepared by simple unit processes such as precipitation, kneading, solvent evaporation, lyophilization and spray drying of solutions or suspensions of the components.
The binding forces of the guest molecule within these inclusion complexes include hydrophobic, van der Waals, hydrogen bonding or dipole interaction.

Cyclodextrins are cyclic oligosaccharides used for the improvement of water-solubility and bioavailability of drugs.
Because of the diverse types of application of cyclodextrins, several types of medicinal products may contain cyclodextrins.
They are used for example in tablets, aqueous parenteral solutions, nasal sprays and eye drop solutions.
Examples of the use of cyclodextrins in medicines on the European market are β-CD in cetirizine tablets and cisapride suppositories, γ-CD in
minoxidil solution, and examples of the use of β-cyclodextrin derivatives are SBE-β-CD in the intravenous antimycotic voriconazole, HP-β-CD in the antifungal itraconazole, intravenous and oral solutions, and RM-β-CD in a nasal spray for hormone replacement therapy by 17β-estradiol.
In Germany and Japan there are infusion products on the market, containing alprostadil (prostaglandin E1, PGE1) with α-CD.
Cyclodextrins are currently not included in the European Commission Guideline on excipients in the label and package leaflet of medicinal products for human use Both α-CD (Alphadex) and β-CD (Betadex) are listed in the European Pharmacopoeia (Ph.Eur.) and γCD is referenced in the Japanese Pharmaceutical Codex (JPC) and will be included in the Ph.Eur. A monograph for HP-β-CD (Hydroxypropyl-betadex) is available in the Ph.Eur. In 2000-2004, α-CD, β-CD and γ-CD were introduced into the generally regarded as safe (GRAS) list of the FDA for use as a food additive.
Alpha- and beta-CD are approved as novel food ingredients by the Commission.
Beta-CD is approved in Europe as a food additive (E 459) with an ADI (acceptable daily intake) of 5 mg/kg/day. SBE-β-CD and HP-β-CD are cited in the FDA's list of Inactive Pharmaceutical Ingredients

Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients.
Nevertheless, developments in cyclodextrin research have shown that some of these hosts can capture and include biomolecules, highlighting fatty acids and cholesterol, which implies that they are not inert and that their action may be used in specific medicinal purposes.
The present review, centered on literature reports from the year 2000 until the present day, presents a comprehensive description of the known biological activities of cyclodextrins and their implications for medicinal applications.
The paper is divided into two main sections, one devoted to the properties and applications of cyclodextrins as active pharmaceutical ingredients in a variety of pathologies, from infectious ailments to cardiovascular dysfunctions and metabolic diseases.
The second section is dedicated to the use of cyclodextrins in a range of biomedical technologies.

Historical Overview
Cyclodextrins (CDs), first reported by Villiers in 1891, have completed their 128th anniversary. Described by Villiers as carbohydrates that precipitate slowly (amidst the fermentation products of starch) in the form of “beautiful radiant crystals”, these molecules have kept as much attractiveness as mystery through the first five decades that followed their discovery.

In the early 50 years of their knowledge to humans, cyclodextrins were the subject of intense scientific curiosity.
Scientists of different groups sought to understand the origins of their formation, their reactivity (including the ability to host other molecules) and, most importantly, their structure. The cyclic nature of cyclodextrins was postulated in 1939; however, this first proposal, based on modelling alone, has also erroneously defined α-CD—the smallest cyclodextrin—as having five glucose units. It was not until 1948, with the adequate purification and crystal structure resolution of each of the native cyclodextrins, that their composition was accurately defined, being of six, seven, and eight glucose units for α-CD, β-CD, and γ-CD .

Cyclodextrin the second half of the 20th century, as the structure and properties of cyclodextrins became known with greater detail, studies were directed towards the exploration of their ability to form inclusion complexes with various molecules.
Cyclodextrins were found to protect sensitive organic guest molecules from volatilization and from oxidation and their solubilizing action on apolar guests made them attractive for a variety of applications.
When the industrial production of cyclodextrins started to make them available in larger quantities and the toxicological safety was ascertained, applications in the pharmaceutical, cosmetic, and food chemistry have blossomed, and, more recently, applications expanded to (re-)emerging areas as nutraceutics and natural products .
Cyclodextrin all of these products, cyclodextrins were essentially regarded as excipients or inert materials.

With the turn of the new millennium, developments in cyclodextrin biomedical research have once more surprised the scientific community by demonstrating that these molecules are not quite so inert and they that may, in fact, be used to treat some human ailments.
Such medicinal properties are the main topic of this review and are presented in detail in Section 2.
Regulatory Status of Cyclodextrins
Native CDs are regarded in Japan as natural products, and for this reason they are used without many restrictions both in medicines and in foods.
In western countries, the ingestion of native cyclodextrins is regulated by the JECFA (Joint WHO/FAO Expert Committee on Food Additives), with the pharmaceutical applications falling under the European Medicines Agency (EMA) in Europe and under the Food and Drug Administration in the United States of America.
Native CDs can be ingested without significant absorption, being thus ‘Generally Regarded As Safe’ by the FDA; they are commonly referred to as molecules with ‘GRAS status’. α-CD and γ-CD can be taken without restrictions while the oral intake of β-CD should be limited to a maximum of 5 mg per kilogram of weight each day. Regarding parenteral use, native cyclodextrins suffer from much stronger restrictions. Indeed, the EMA recommends against the administration of α-CD and β-CD directly into the bloodstream due to renal toxicity.
Cyclodextrin addition, native CDs are known to cause hemolysis in vitro, at concentrations of 6, 3, and 16 mM for α-, β-, and γ-CDs, respectively, due to extraction of phospholipids and cholesterol from the erythrocyte membrane.

Native CDs can be functionalized to afford a large variety and number of derivatives, surpassing 1500 different molecules according to a report of 2012.
Of these, only a few are approved for human use in the fields of pharmaceutics.
The U.S. Food and Drug Administration (FDA) lists 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2-hydroxypropyl-γ-CD (HPγCD) as approved inert materials (excipients), with HPβCD being suited for oral and intravenous administration while HPγCD can only be used in topical products and in a maximal concentration of 1.5% (w/v).
Within O-methylated CDs, the approval status varies from one molecule to the next.
For instance, heptakis-2,3,6-tris-O-methyl β-CD (TRIMEB) is deemed unsafe for human use due to its hemolytic action and renal toxicity.
Cyclodextrin sister cyclodextrin, heptakis-2,6-di-O-methyl-β-CD (DIMEB), also features some toxicity, mostly targeting the liver: Doses of 300 mg/kg in mice caused elevated levels of glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT), two biomarkers of hepatic injury.
Despite this, DIMEB is approved by the FDA for commercial use in a few injectable vaccines , probably due to the fact that it is present in low amounts in such products.
Cyclodextrins that have undergone O-methylation in random positions have different safety profiles, according to the different degrees of substitution. RAMEB (from randomly methylated beta-cyclodextrin), with an average of 1.8 methoxyl groups per glucose unit, has some hydrolytical action on erythrocytes, as well as renal toxicity that is higher than that of the parent βCD.
For these reasons, RAMEB is not recommended for parenteral use by the EMA.
CRYSMEB (named after the fact that it is a crystalline solid, crystalline methylated beta-cyclodextrin) has a deliberately low substitution degree (average of 0.56 methyl groups per glucose unit, i.e., only four methyl groups in each CD molecule) because it was designed for high biotolerability.
CRYSMEB does not cause hemolysis and it is already approved for dermal applications and as an ingredient in cosmetics.
Another biocompatible CD is sulfobutyl ether β-CD (SBEβCD), developed to be non-nephrotoxic and present in several FDA-approved marketed medications for both oral and intravenous administration

Cyclodextrins consist of multiple glucose building blocks linked together in a ring.
Depending on the size of the ring, a distinction is made between α-cyclodextrin with six, β-cyclodextrin with seven and γ-cyclodextrin with eight glucose units.
WACKER is the only company in the world to produce all three naturally occurring cyclodextrins, marketing them under the trade names CAVAMAX® W6 (α-cyclodextrin), W7 (β-cyclodextrin) and W8 (γ-cyclodextrin).

The cyclodextrin derivatives produced by modifying these α-, β- and γ-cyclodextrins by hydroxypropylation or methylation are marketed by WACKER under the name CAVASOL®.

Thanks to the special properties of cyclodextrins, they enable a variety of applications.
For example, cyclodextrins can be used for stabilizing sensitive substances, for controlled release of bioactives, masking unwanted aromas, rheology control or for improving solubility and bioavailability. And that is only the start of the potential offered by cyclodextrins.

Cyclodextrins are cyclic oligosaccharides with the shape of a hollow truncated cone.
Their exterior is hydrophilic and their cavity is hydrophobic, which gives cyclodextrins the ability to accommodate hydrophobic molecules/moieties in the cavity.
This special molecular arrangement accounts for the variety of beneficial effects cyclodextrins have on proteins, which is widely used in pharmacological applications.
We have studied the interaction between β‐cyclodextrin and four non‐carbohydrate‐binding model proteins: ubiquitin, chymotrypsin inhibitor 2 (CI2), S6 and insulin SerB9Asp by NMR spectroscopy at varying structural detail.
We demonstrate that the interaction of β‐cyclodextrin and our model proteins takes place at specific sites on the protein surface, and that solvent accessibility of those sites is a necessary but not compelling condition for the occurrence of an interaction.
If this behaviour can be generalized, it might explain the wide range of different effects of cyclodextrins on different proteins: aggregation suppression (if residues responsible for aggregation are highly solvent accessible), protection against degradation (if point of attack of a protease is sterically ‘masked’ by cyclodextrin), alteration of function (if residues involved in function are ‘masked’ by cyclodextrin).
The exact effect of cyclodextrins on a given protein will always be related to the particular structure of this protein.

Cyclodextrins (CDs) are natural cyclic oligosaccharides that are produced by enzymatic degradation of starch.
There are three native CDs designated αCD, βCD and γCD, which are composed of 6, 7 and 8 D-glucopyranose units linked by α-(1, 4) glycosidic, respectively .
The molecules are commonly described as truncated cone, bucket-like or donut-shaped, with a hydrophilic outer surface and a relatively hydrophobic inner cavity that allows entrapment of small hydrophobic drug molecules or hydrophobic moieties of larger molecules , thereby providing drugs with new physicochemical characteristics without altering their intrinsic properties.
Table 1 summarizes the characteristics of different CDs.
Natural CDs are preferred for complexation; however, their usability is limited by the small cavity size of αCD, poor aqueous solubility of βCD and low productivity of γCD .
Derivatized CDs can be obtained by substituting their hydroxyl groups with desired functional moieties.
Methyl-(MeβCD and MeγCD) 4, 5, hydroxypropyl-(HPαCD, HPβCD and HPγCD) 6-8 and sulphobutylether (SEBβCD) derivatives are frequently found in pharmaceutical products and have improved solubility and inclusion capacity over natural CDs.
Pharmaceutical applications of both natural CDs and their derivatives are common when drug/CD complexes are used to increase drug solubility, improve organoleptic properties , enhance drug permeation and increase drug stability, resulting in increased product shelf-life and drug bioavailability.
In addition, spontaneous self-assembly of drug/CD complexes into aggregates can lead to innovative drug delivery systems, such as CD-containing liposomes and microspheres as well as micro- and nanoparticles .
Polymerized CDs (e.g. Epi-αCD and Epi-βCD) have also been synthesized to enhance the self-assembly ability of CDs, and to strengthen their interactions with drugs and biological membranes.
Compared with other pharmaceutical excipients, CDs have been shown to reduce the toxicity of several drugs and are biocompatible.
As a result, they are appealing for use in the development of pharmaceutical formulations, including the reformulation of existing drug products.

Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds.
Cyclodextrins are produced from starch by enzymatic conversion.
They are used in food, pharmaceutical, drug delivery, and chemical industries, as well as agriculture and environmental engineering.
Cyclodextrins are composed of or more α-D-glucopyranoside units linked 1->4, as in amylose (a fragment of starch).
The largest cyclodextrin contains 1,4-anhydroglucopyranoside units, while as a poorly characterized mixture, at least 150-membered cyclic oligosaccharides are also known.
Typical cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape: α (alpha)-cyclodextrin: glucose subunits β (beta)-cyclodextrin: glucose subunits γ (gamma)-cyclodextrin: glucose subunits

What Are Cyclodextrins and Why Are They of Interest?
The CDs of biomedical and pharmaceutical interest are cyclic oligosaccharides made up of six to eight dextrose units (α-, β-, and γ-CDs, respectively) joined through one to four bonds.
These so-called “parent CDs” have themselves been used in food and pharmaceutical products for many years, although their use in the United States has been more limited than in Japan and Europe.
A generalized chemical structure of these CDs is shown in Table 1, which also contains the names and abbreviations of some CDs commonly discussed in CD-related biomedical articles.

Cyclodextrin pharmaceutical uses of CDs, which are the focus of this article, have been discussed in numerous reviews and books and are a major subject of a biennial International Cyclodextrin Symposium.
In addition, the Society of Cyclodextrins, Japan, symposium is held every year.
Cyclodextrin reader is directed to these publications and proceedings from these symposia for both a historical perspective and a more comprehensive discussion than can be accomplished here.

CDs are useful pharmaceutically because they can interact with drug molecules to form inclusion complexes.
This formation of an inclusion complex, often a 1:1 interaction, is usually described by Equation 1 or as in Scheme 1, although higher order complexes are often seen or postulated.

In forming the complex, the physicochemical and biological properties of the drug can be altered to effect an advantage.

What can Cyclodextrins Do and What can’t they Do?
In forming inclusion complexes, major changes in drug candidate properties, including enhanced solubility, physical and chemical stability, and other physicochemical properties, have been well documented.
These changes have then resulted in better biological performance, and thus, in the use of CDs in various commercially successful pharmaceutical products.

Ever since the discovery of cyclodextrins, a family of cyclic oligosaccharides based on α (1 → 4) linkage among glucopyranose subunits, these versatile supramolecular hosts have received tremendous attention for scientific explorations.
Due to their property of forming host–guest type inclusion complex, cyclodextrins and their synthetic derivatives exhibit wide range of utilities in different areas viz. pharmaceuticals, drug delivery systems, cosmetics, food and nutrition, textile and chemical industry etc.

Objective: The purpose of this review is to highlight properties, advantages, recent studies and versatile benefits of cyclodextrins and to re-strengthen their prospective applications in novel directions for future research.

Methods: This article summarizes a variety of applications of cyclodextrins in various industrial products, technologies, analytical and chemical processes and recent industrial advancements by extensively literature search on various scientific databases, Google and websites of various associated pharmaceutical industries and patenting authorities across the world.

Results and conclusion: Due to possibility of multidimensional changes in physical and chemical properties of molecules upon inclusion complexation in cyclodextrins, these compounds are of great commercial interest and may offer solution to many of the scientific problems of the current world.

Cyclodextrins (CDs) are defined as the class of cyclic oligosaccharides which contains glucopyranose units and which are linked to each other by α-(1,4) bonds.
Three naturally occurring cyclodextrins, also known as first generation CDs or parent CDs, are: α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD), containing 6, 7 and 8 glucopyranose units, respectively.

Although, the natural CDs and their complexes are hydrophilic, but their aqueous solubility is reported to be limited, mainly in the case of β-CD.
Cyclodextrin is because CD molecules binds relatively strongly in their crystal state.
CDs contain glucopyranose units which further consists of three free hydroxyl groups differing on the basis of both functions as well as reactivity.
The different reaction conditions like pH, temperature and reagents affect the relative reactivity of C-2 and C-3 secondary and the C-6 primary hydroxyls of the CD molecule.
With the substitution of hydrogen and hydroxyl group with large number of substituting groups, such as alkyl, hydroxyl alkyl, carboxy alkyl, amino, thio, tosyl, glucosyl, maltosyl etc., and thousands of ethers, esters, anhydro, deoxy, acidic and basic etc., 21 hydroxyl groups of β-CD can be modified to obtain different CD derivatives by chemical and enzymatic reactions.

Such derivatizations are done to accomplish the following objectives:
to enhance the solubility of different CD derivatives and their complexes;
to improve the fitting and/or the association between the CD and its guest, with concomitant stabilization of the guest, reducing its reactivity and mobility;
to achieve insoluble, immobilized CD-containing structures and polymers, e.g. for chromatographic purposes.
CD derivatives are mainly categorized as:
(a) chemically modified CD derivatives and
(b) natural enzymatically modified CD derivatives.

Enzymatically modified CD derivatives are formed with the help of pullulanase enzyme and are known as branched CDs.
When the hydroxyls of β-CD are made to react with a chemical reagent, the substitution occurs and a heterogeneous product is generated.
The extent to which substitution occurs can be defined and expressed in different ways as follows:

Degree of substitution: It is defined as the number of the hydroxyl groups in a glucose moiety of CD molecule that has been substituted.
Therefore, it can be ranged from 1 to 3. The average degree of substitution (DS) is the average number of hydroxyl groups being substituted in a glucose unit of CD.
Cyclodextrin value can vary from 0 to.

Molar degree of substitution: Cyclodextrin is the critical parameter, which is mainly defined as the average number of substituent’s that completely reacts with one glucopyranose repeat unit.
If the molar degree of substitution (MS) value is equal to 0, then no substitution or up to 3, when two or more substituents react and form oligomeric or polymeric side chains.

CD derivatives like hydroxypropyl derivatives of β and γ-CD (HP-β-CD and HP-γ-CD), randomly methylated β-CD (RM-β-CD), sulfobutylether β-CD sodium salt (SBE-β-CD) and the branched CDs, such as maltosyl-β-CD (M-β-CD) are of great pharmaceutical interest.

Cyclodextrins (CDs) are cyclic oligosaccharides, formed by α-1,4-linked glucose units, with a hydrophilic outer surface and a lipophilic central cavity.
α-Cyclodextrin (αCD), β-cyclodextrin (βCD), and γ-cyclodextrin (γCD) are natural products that can be found in small amounts in various fermented consumer products, such as beer.
Although the unsubstituted natural αCD, βCD, and γCD, and their complexes, are hydrophilic their solubility in aqueous solutions is somewhat limited, especially that of βCD.
Consequently the more soluble βCD derivatives, such as 2-hydroxypropyl-βCD (HPβCD) and sulfobutylether βCD sodium salt (SBEβCD), are preferred for use in aqueous pharmaceutical solutions, such as parenteral drug formulations, even though both αCD and γCD can be found at low concentrations in parenteral formulations.
Monographs for αCD, βCD, and γCD and two βCD derivatives are in the European Pharmacopoeia and the United States Pharmacopeia/National Formulary (Table 1).
CDs are included in over 40 marketed pharmaceutical products worldwide, in addition to numerous food, cosmetic, and toiletry products.

Due to their ability to change physiochemical properties of drugs and other compounds, CDs are frequently referred to as enabling pharmaceutical excipients.
CDs enable delivery of poorly water-soluble and chemically-unstable drugs to the body.
Hence, CDs are able to convert biologically-active compounds that lack drug-like physiochemical properties into therapeutically-effective drugs.
CDs (referred to as host molecules) are able to form inclusion complexes with drugs (referred to as guest molecules) by taking part of a drug molecule into the central CD cavity.
This will change the physiochemical properties of the included drug.
Formation of a drug/CD inclusion complex can, for example, increase the aqueous solubility of the drug, increase its chemical and physical stability, and enhance drug delivery through biological membranes.
No covalent bonds are formed or broken during the complex formation and, in aqueous solutions, drug molecules bound within the CD inclusion complex are in dynamic equilibrium with free drug molecules (Figure 1).
Drug molecules are readily released from the complex upon media dilution or by competitive complexation.
One or more drug molecules can form a complex with one CD molecule and one or more CD molecules can form a complex with one drug molecule.
However, most commonly, one drug molecule (D) forms a complex with one CD molecule.
The stoichiometry of the drug/CD complex (D/CD) is then 1:1 and the equilibrium constant (K1:1) defined as

Cyclodextrin molecular structure of cyclodextrins creates a bucket-like cavity that can function to complex with molecules or functional groups on molecules.
Cyclodextrin substitution of hydroxyl groups on native cyclodextrins to make hydroxypropyl-ß- or hydroxypropyl-γ-cyclodextrins (HPBCD or HBGCD) significantly enhances their solubility and makes them more suitable for drug solubilization.
This mechanism makes the Cavitron and CAVASOL HPBCDs and HPGCDs capable of masking unpleasant taste/odor and stabilizing drugs that are prone to degradation, and also can increase solubility of poorly soluble compounds in oral drug delivery systems.
Purification of the Cavitron cyclodextrins to remove endotoxins allows their use for solubilization of drugs for parenteral drug products.

The regulatory compliance information for all Ashland products varies by product family and grade.
For specific data about the grade you are interested in please refer to our Excipient Information Package, now called PRD, and the Certificate of Analysis (COA).

Cyclodextrin book is devoted to the highly versatile and potential ingredient Cyclodextrin, a family of cyclic oligosaccharides composed of ?-(1,4)-linked glucopyranose subunits.
Cyclodextrin molecular complexation phenomena and negligible cytotoxic effects attribute toward its application such as in pharmaceuticals, cosmetics, food, agriculture, textile, separation process, analytical methods, catalysis, environment protection, and diagnostics.
Efforts have also been made to concentrate on recent research outcomes along with future prospects of cyclodextrins to attract the interest of scientists from the industry and academia.
Cyclodextrin contributions of the authors are greatly acknowledged, without which this compilation would not have been possible.

Synonym(s)
BCD
betaCD
Cyclodextrin B
beta-Schardinger dextrin

Functional Classes
Carrier
Stabilizer
Thickener

Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility.
These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult.
An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system.
This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery.
Cyclodextrin present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents.
These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells.
Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency.
In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents.

A homologous group of cyclic GLUCANS consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates.
The enzyme is produced by certain species of Bacillus.
Cyclodextrins form inclusion complexes with a wide variety of substances.

Synonyms
Celdex;
Celdex CH 20;
Celdex CH 30;
Celdex SH 20;
Celdex SH 40;
Celdex SH 50;
Cycloamylose;
Rhodocap L 20;
Ringdex P
CAS Registry Number: 12619-70-4

Product Name: CYCLODEXTRIN
Molecular Weight: 0
Mol File: 12619-70-4

Cyclodextrins (CDs) are cyclic, nonreducing oligosaccharides linked through α-1,4 glycosidic bonds.
Due to steric repulsion, CDs have more than six glucose units. α-, β-, and γ-CDs contain six, seven, and eight glucose units, respectively.
The chair conformation of glucopyranose units results in CD molecules having a truncated cone shape, with a somewhat hydrophobic central cavity and a hydrophilic outer surface.
Cyclodextrin structure enables them to interact with poorly watersoluble compounds, thereby solubilizing them via the formation of host–guest inclusion complexes.
Normally, the hydrophobic chains of amphiphiles are included in host–guest complexes with 1:1 or 2:1 stoichiometry with high binding constants.
In the late 1960s, the appearance of polyether and realization of its recognition capacity created the concept of host–guest chemistry.
CDs possess excellent properties in terms of molecular recognition, molecular interaction,
and molecular aggregation, and many molecules of a suitable size can undergo inclusion complexation with CDs.
The wide availability and low cost of CDs facilitates their use in various fields including analysis, catalysis, and surface chemistry, and in many industries such as pharmaceuticals, cosmetics, textiles, and food.
In recent times, supramolecular chemistry has attracted considerable attention as an important subdiscipline of chemistry that develops molecular building blocks for the construction of novel systems with intriguing properties that differ from their separate components .
CDs are generally composed of both hydrophilic and hydrophobic moieties.
Through hydrophobic and other noncovalent interactions, CD molecules can form various self-assembled structures in aqueous solutions including micelles, vesicles, lyotropic liquid crystals, and gels, all of which have found many applications in the fields of cosmetics, drug delivery, materials synthesis, and microreactors.
A great deal of attention has been given to the construction of novel ordered and functional assemblies due to their delicate and highly organized aggregate structures.
Different approaches have been developed including molecular structure modification to tune the amphiphile hydrophilic/hydrophobic balance and introduce molecular motifs such as host molecules to form inclusion complexes, and CDs are now considered effective modulators of the self-assembly
of amphiphiles.
Host–guest interactions of CDs are derived from many aspects including hydrophobic interactions, Van der Waals interactions, the ring tension of the CD, the surface tension of the solvent, and the effect of hydrogen bonds.
Numerous guest molecules of an appropriate size are generally able to form inclusion complexes with CDs.
Polymeric systems based on CDs and certain guest molecules have been developed in recent years.
For example, the application of nanoparticle and micelle macromolecular materials has attracted widespread attention in medical and biological fields, especially for continuous drug release, targeted delivery, and tissue engineering.
Many stimuli-responsive polymeric networks with novel structures have been designed through chemical cross-linking, physical aggregation, and other means.
Polymeric systems based on CDs and guest molecule inclusion complexes can vary in structure and may be linear, branched, comb-like, or hyperbranched, as shown in.
These structures can subsequently form higher-order structures such as peels, micelles, vesicles, and tubes, which can be used in many ways.
Supramolecular systems often resemble naturally occurring molecules in structure and function; hence they are considered biomimetics.
Key life processes including photosynthesis and oxygen storage are dependent on complex formation via supramolecular building molecules such as porphyrinoids