Hubbry Logo
CyclodextrinCyclodextrinMain
Open search
Cyclodextrin
Community hub
Cyclodextrin
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Cyclodextrin
Cyclodextrin
Cyclodextrin
View on Wikipedia
from Wikipedia

Chemical structure of the three main types of cyclodextrins.

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.[1]

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:

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]
β-Cyclodextrin

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 α-1,4 linkages between glucose monomers. Cyclodextrins were also shown to enhance mucosal penetration of drugs.[6]

Chromatography

[edit]

β-cyclodextrins are used to produce stationary phase media for HPLC separations.[7]

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 β-cyclodextrins "trap" odor-causing compounds, thereby reducing the odor.[1]

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]
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. 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 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.[12] Purification of the three types of cyclodextrins takes advantage of the different water solubility of the molecules: β-CD which is poorly water-soluble (18.5 g/L or 16.3 mM at 25 °C) 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. Some researchers have developed dedicated processes that can produce alpha-, beta- or gamma-cyclodextrin specifically[13]. This 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.[14]

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.[15]

Both β-cyclodextrin and methyl-β-cyclodextrin (MβCD) remove cholesterol from cultured cells. The methylated form MβCD was found to be more efficient than β-cyclodextrin. The 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.[16]

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.[17][18] 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.[19]

Research

[edit]
Synthesis of acoustically active nanoparticles for 'Nanoparticle Mediated Histotripsy'.

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 ([AuBr4]-).[20]

β-Cyclodextrin complexes with certain carotenoid food colorants have been shown to intensify color, increase water solubility and improve light stability.[21][22]

Complexes formed between β-cyclodextrin and adamantane derivatives have been used to make self-healing materials, such as hydrogels[23] and low-friction surfaces.[24]

Using the host-guest interaction between β-Cyclodextrin and Perfluorohexane, acoustically active nanoparticles were created.[25] These nanoparticles were combined with histotripsy, leading to the development of Nanoparticle-Mediated Histotripsy (NMH). NMH addresses limitations of traditional histotripsy, such as non-selectivity and the requirement for high pressure.[26] This promising new method has potential applications in cell ablation for various purposes, including cancer treatment.[27]

History

[edit]
Space filling model of β-cyclodextrin.

Cyclodextrins were called "cellulosine" when first described by A. Villiers in 1891.[28] 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,[29] 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.[30] Among the processes used for complexation, the kneading process seems to be one of the best.[31]

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 β-cyclodextrin for the prevention of atherosclerosis,[32] age-related lipofuscin accumulation[33] and obesity encounter an obstacle in the form of damage to the auditory nerve[34] and nephrotoxic effect.[35]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Cyclodextrin

View on Grokipedia
from Grokipedia
Cyclodextrins are cyclic oligosaccharides produced from by enzymatic degradation, consisting of six or more D-glucopyranose units linked by α-(1,4) glycosidic bonds, which form a toroidal with a hydrophobic inner cavity and hydrophilic outer surface. This unique structure enables cyclodextrins to form host-guest inclusion complexes, encapsulating hydrophobic molecules to improve their , stability, and . First discovered in 1891 by Antoine Villiers during the bacterial digestion of , cyclodextrins were isolated as crystalline products and later characterized by Franz Schardinger, who identified alpha- and beta-forms using Bacillus amylobacter enzymes. The most common natural variants—α-cyclodextrin (six glucose units), β-cyclodextrin (seven units), and γ-cyclodextrin (eight units)—differ in cavity size, affecting their complexation capacity and ; β-cyclodextrin, for instance, has limited aqueous but forms stable complexes with many pharmaceuticals. In pharmaceuticals, cyclodextrins serve as excipients to enhance the delivery of poorly soluble drugs via oral, parenteral, and topical routes, reducing irritation and masking bitterness. Beyond medicine, they find applications in for flavor stabilization and reduction, as well as in and for pollutant sequestration.

Chemical Structure and Properties

Molecular Architecture

Cyclodextrins are cyclic oligosaccharides composed of α-D-glucopyranose units linked by α-(1→4) glycosidic bonds, forming a closed ring. The native forms include α-cyclodextrin (six glucose units), β-cyclodextrin (seven units), and γ-cyclodextrin (eight units). This ring structure adopts a macrocyclic configuration where each glucose residue assumes the ⁴C₁ chair conformation. The overall architecture resembles a truncated cone or toroid, with a wider secondary hydroxyl face (C2 and C3 positions) and a narrower primary hydroxyl face (C6 positions). The exterior surface is hydrophilic, featuring hydroxyl groups that enable hydrogen bonding with water, while the internal cavity is hydrophobic, lined primarily by the skeletal carbon and hydrogen atoms along with the glycosidic oxygen bridges. This apolar cavity, approximately 4.7–5.3 Å (α-CD), 6.0–6.5 Å (β-CD), and 7.5–8.3 Å (γ-CD) in diameter, facilitates host-guest inclusion complexes with suitably sized hydrophobic molecules. Intramolecular hydrogen bonding between the secondary hydroxyl groups on one side stabilizes the rigid , contributing to the slight bending of the ring and the conical asymmetry. The primary hydroxyl groups project outward, enhancing , whereas the cavity's electron-rich environment from glycosidic oxygens influences selectivity in complexation. These features underpin cyclodextrins' utility in molecular recognition and encapsulation.

Physical and Chemical Characteristics

Cyclodextrins are obtained as white to off-white crystalline powders that are odorless and possess a mildly taste. They exhibit low solubility in organic solvents such as , , and acetone, but varying degrees of aqueous solubility depending on the specific type, with β-cyclodextrin showing the lowest due to extensive intramolecular bonding among its secondary hydroxyl groups. Thermally, native cyclodextrins demonstrate high stability, decomposing without melting at temperatures exceeding 250–300 °C; for instance, β-cyclodextrin decomposes below 260 °C under conventional heating, while α- and γ-cyclodextrins require higher temperatures approaching 300 °C or more. The chemical stability of cyclodextrins is pronounced in neutral and alkaline environments, with reported pKa values ranging from 12.1 to 13.5, rendering them resistant to degradation at physiological levels. In contrast, exposure to strong acidic conditions (low ) promotes of the glycosidic oxygen atoms, increasing susceptibility to hydrolytic cleavage of the α-1,4-glycosidic bonds, particularly at elevated temperatures. This pH- and temperature-dependent stability influences their applications, as complex stability constants for inclusion compounds decrease under acidic or high-temperature conditions. A defining chemical characteristic is the formation of inclusion complexes, enabled by the toroidal molecular architecture featuring a hydrophobic internal cavity lined with C-H bonds and glucosidic oxygens, contrasted by a hydrophilic exterior rich in hydroxyl groups. Guest molecules, typically hydrophobic or poorly water-soluble compounds, are accommodated within the cavity through non-covalent interactions, including van der Waals forces, hydrophobic effects from water displacement, and occasionally hydrogen bonding or electrostatic contributions. This complexation enhances the aqueous , chemical stability, and of the guest while masking odors or tastes, without altering the cyclodextrin's inherent properties. The primary native cyclodextrins—α (6 glucose units), β (7 units), and γ (8 units)—differ in cavity size, molecular weight, and , as summarized below:
Propertyα-Cyclodextrinβ-Cyclodextrinγ-Cyclodextrin
Molecular formulaC₃₆H₆₀O₃₀C₄₂H₇₀O₃₅C₄₈H₈₀O₄₀
Molecular weight (g/mol)972.811351297
Water (g/100 mL, 25 °C)14.51.8523.2
These variations arise from ring size: the smaller α-cavity limits guest accommodation to smaller molecules, while the larger γ-cavity accommodates bulkier guests, influencing complexation efficiency and selectivity.

Types and Derivatives

Native Cyclodextrins

Native cyclodextrins are the unmodified cyclic oligosaccharides α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), and γ-cyclodextrin (γ-CD), composed of six, seven, and eight α-D-glucopyranose units, respectively, linked by α-(1→4) glycosidic bonds. These structures form a truncated cone-shaped with a hydrophobic cavity lined by the C3-H, C5-H, and C6-H groups and a hydrophilic exterior due to the hydroxyl groups on the primary and secondary faces. The cavity depth is approximately 7.9 Å across all three, enabling host-guest inclusion complexes with non-polar molecules of compatible size. The primary differences among native cyclodextrins arise from their cavity dimensions and profiles, which influence their complexation capacities. α-CD accommodates smaller guests, β-CD mid-sized ones like many pharmaceuticals, and γ-CD larger molecules. β-CD exhibits notably lower due to intramolecular in its , which hinders dissolution, whereas α-CD and γ-CD form less stable lattices, enhancing their .
Propertyα-Cyclodextrinβ-Cyclodextrinγ-Cyclodextrin
Glucose units678
Molecular weight (g/mol)972.91135.01297.1
Cavity diameter (Å)4.7–5.36.0–6.57.5–8.3
Aqueous solubility (g/L at 25°C)14518.5232
Native cyclodextrins demonstrate high thermal stability, with decomposition temperatures above 250°C, and in neutral to mildly alkaline conditions, though they hydrolyze under acidic or enzymatic . Their and low toxicity stem from their derivation from , making them suitable for diverse applications, though β-CD's limited often necessitates derivatization for enhanced utility.

Chemically Modified Derivatives

Chemically modified cyclodextrins are obtained by substituting hydroxyl groups on the native cyclic structures, primarily at the 2-, 3-, and 6-positions, to overcome limitations such as low aqueous (e.g., β-cyclodextrin of 18.5 mg/mL at 25°C) and potential in parenteral applications. These modifications, including etherification and sulfation, enhance water , stability against , and inclusion complexation capacity while altering pharmacokinetic properties like renal clearance. For instance, substitution degrees (DS) typically range from 0.6 to 7 per glucose unit, with higher DS correlating to increased but potentially reduced cavity accessibility for guest molecules. Hydroxypropyl-β-cyclodextrin (HPβCD) is produced via of β-cyclodextrin with under alkaline conditions, yielding an amorphous with an average DS of 0.8–1.0 hydroxypropyl groups per glucose unit, resulting in exceeding 600 mg/mL. This modification disrupts the crystalline lattice of native β-cyclodextrin, improving dissolution rates and enabling complexation with poorly soluble drugs like , where phase-solubility studies show linear increases in drug proportional to HPβCD concentration. HPβCD exhibits low (LD50 >5 g/kg orally in rats) and is approved for oral, topical, and parenteral use, though its solubilizing efficiency decreases with higher DS due to steric hindrance in the hydrophobic cavity. Sulfobutylether-β-cyclodextrin (SBEβCD), commercially known as Captisol, features an average of 6–7 sulfobutyl groups (-CH2CH2CH2CH2SO3Na) per cyclodextrin molecule, introduced through reaction with 1,4-butane sultone, conferring anionic character and solubility over 500 mg/mL (more than 50-fold that of β-cyclodextrin). The negatively charged groups enhance electrostatic repulsion for improved stability and reduce compared to native forms, making it suitable for intravenous formulations like injections, where it increases drug loading without precipitation. (NMR) analysis confirms substitution predominantly at the 6-position, optimizing cavity integrity for inclusion while minimizing . Methylated β-cyclodextrins, such as randomly methylated β-cyclodextrin (RMβCD) with ~1.7–2.0 methyl groups per glucose, are synthesized by treating β-cyclodextrin with methyl iodide or under basic conditions, achieving solubilities up to 600 mg/mL and strong complexation due to reduced hydrogen bonding. These derivatives excel in solubilizing lipophilic compounds via van der Waals interactions in the apolar interior but pose risks for parenteral use owing to disruption (e.g., higher than HPβCD in cell assays), limiting them primarily to oral and topical applications like enhancing of . Permethylated variants (heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin) further amplify , aiding chiral separations in . Other derivatives include amino-substituted and quaternary ammonium cyclodextrins for cationic properties, though less common due to synthetic complexity and potential instability; these are explored for targeted delivery but lack widespread regulatory approval. Overall, modifications are tailored via regioselective (e.g., using tosyl groups for 6-position specificity), with analytical techniques like and NMR verifying DS and substitution patterns to ensure reproducibility.

Synthesis and Production

Enzymatic Production from

Cyclodextrins are produced industrially from through enzymatic cyclization catalyzed by cyclodextrin glucanotransferase (CGTase), a bacterial that performs intramolecular transglycosylation on linear α-1,4-glucan chains to form cyclic oligosaccharides. This process exploits the enzyme's specificity for generating rings of 6 to 8 glucose units, corresponding to α-, β-, and γ-cyclodextrins, respectively. CGTase is typically derived from mesophilic or thermophilic species, such as Bacillus circulans for β-cyclodextrin production or Bacillus stearothermophilus for broader cyclodextrin mixtures. The production begins with starch gelatinization in water at temperatures around 90–105°C to disrupt granular structure, followed by liquefaction using thermostable α-amylase to hydrolyze starch into maltodextrins and reduce viscosity, yielding a substrate of short to medium-length glucan chains optimal for CGTase action. CGTase is then added at concentrations of 0.5–2% relative to starch dry weight, with reactions conducted at 50–70°C and pH 5.5–7.0 for 24–72 hours, depending on enzyme stability and desired cyclodextrin type. The enzyme's cyclization mechanism involves cleavage of an α-1,4-glycosidic bond and reformation into a cyclic structure, minimizing hydrolysis and favoring ring closure over linear products. Yields vary by process optimization; conventional batch methods achieve 20–40% conversion of dry weight to cyclodextrins, with β-cyclodextrin often predominant (up to 60% of total CDs) using selective CGTases, though mixtures require downstream separation. Advanced approaches, such as continuous systems or biofilm-immobilized CGTase, enhance productivity to over 100 g/L cyclodextrin while enzymes, reducing costs in large-scale operations. Alternative raw , like corn or seed, can be used without pretreatment in attrition-enhanced reactors, improving efficiency by direct mechanical disruption during enzymatic action. Purification typically follows via with organic solvents or selective adsorption, but enzymatic selectivity during production minimizes linear byproducts.

Post-Synthesis Modifications

Post-synthesis modifications of cyclodextrins entail chemical derivatization of enzymatically produced native forms (α-, β-, and γ-cyclodextrins) to address limitations such as the low aqueous of β-cyclodextrin (18.5 g/L at 25 °C), which restricts its utility in pharmaceutical and industrial applications. These modifications primarily target the hydroxyl groups at C-2 and C-3 (secondary rim) and C-6 (primary rim), introducing substituents via etherification, esterification, or other reactions to enhance , stability, and guest inclusion capacity. Derivatization often yields amorphous products with degrees of substitution (DS) ranging from 0.5 to 10, controlled by reactant ratios, temperature, and base catalysis (e.g., NaOH or NaH). Etherification techniques dominate , including with alkyl halides or under conditions for methylated derivatives like randomly methylated β-cyclodextrin (RAMEB), which exhibits solubility >200 g/L. Hydroxyalkylation involves ring-opening, as in the synthesis of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by reacting β-CD with in alkaline aqueous media at 40–60 °C for 4–8 hours, producing a mixture of positional and substitution isomers with DS typically 4–8 and solubility up to 600 g/L. Anionic derivatives, such as sulfobutylether-β-cyclodextrin (SBE-β-CD), are formed via nucleophilic attack on 1,4-butanesultone in basic media, achieving DS of 6–7 sulfobutyl groups and solubilities exceeding 500 g/L, approved by the FDA for parenteral use since 2001. Selective modifications enable precise functionalization, often requiring multi-step protection-deprotection sequences; for example, primary C-6 hydroxyls are tritylated, allowing secondary rim reactions before detritylation with . Esterification with acid chlorides or anhydrides yields acyl derivatives, while oxidation (e.g., with ) targets primary alcohols to aldehydes or carboxylic acids. Emerging solvent-free mechanochemical methods, using ball milling with bases and reagents, reduce environmental impact and improve yields for hydroxyalkyl and amino derivatives, as demonstrated in 2021 studies achieving DS comparable to conventional routes without high-boiling solvents. These techniques underpin over 100 commercial CD derivatives, with hydroxypropyl and sulfobutyl variants comprising the majority in drug formulations.

Historical Development

Early Discovery

Antoine Villiers, a French pharmacist and , first isolated a crystalline substance from the enzymatic degradation of by amylobacter in 1891, during experiments on reduction under ferment action. This product, obtained in low yield—approximately 3 grams from 1 of —was termed "cellulosine" and represented the initial observation of what later proved to be cyclodextrins, though its structure and properties remained unidentified at the time. In 1903, Austrian biochemist Franz Schardinger advanced this finding by systematically studying starch degradation by thermophilic bacteria, such as Bacillus macerans, which produced dextrinizing enzymes. Schardinger isolated two distinct crystalline dextrins from these digests between 1903 and 1911, demonstrating their ability to form crystalline complexes with iodine, , and other compounds—properties that distinguished them from linear dextrins. These isolates corresponded to α-cyclodextrin (six glucose units) and β-cyclodextrin (seven glucose units), though their cyclic nature was not elucidated until later crystallographic studies in . Schardinger's enzymatic production method and complexation observations established the foundational chemistry of cyclodextrins, earning him recognition as a pioneer despite initial interest limited to bacterial metabolism rather than practical applications. Early investigations from to the mid-1910s focused primarily on production yields and basic solubility behaviors, with yields remaining low (under 1% of weight) due to inefficient bacterial processes. Researchers like Pringsheim explored complexes in the , confirming unique binding capacities, but structural confirmation awaited analyses by Freudenberg and others in 1935, revealing the toroidal, hydrophobic cavity enabling host-guest inclusion. These discoveries occurred amid broader enzymology studies, with cyclodextrins initially viewed as microbial byproducts rather than versatile molecules.

Commercialization and Scaling

Commercial production of cyclodextrins commenced in the mid-, driven by refinements in enzymatic processes utilizing cyclodextrin glycosyltransferase (CGTase) derived from species to convert into cyclic oligosaccharides. Pilot-scale efforts in began around 1960, primarily targeting β-cyclodextrin for initial applications, though limited by low yields and high purification costs that restricted output to small quantities suitable only for . By the late , multiple manufacturers initiated industrial-scale operations, marking the transition from laboratory synthesis to viable commodity production. Scaling accelerated in the mid-1980s through process optimizations, including improved CGTase specificity, techniques, and downstream separation methods like and , which reduced production costs to 10-15 USD per and enabled output in large quantities. These advancements addressed key bottlenecks such as instability at high temperatures, variable cyclodextrin ratios (favoring β over α or γ forms), and energy-intensive purification, with annual global production rising from hundreds to several thousand tons by the . Leading producers, including AG (marketing under CAVAMAX) and , invested in dedicated facilities to supply native and modified variants for pharmaceutical and sectors. Further enhancements in the 1990s and 2000s involved recombinant CGTase expression in hosts like for higher activity, alongside innovations such as for enzyme reuse and immobilized biocatalysts, which minimized waste and boosted conversion efficiencies beyond 70% in optimized systems. For γ-cyclodextrin, which poses greater challenges due to high and lower enzymatic preference, specialized strains and surface-displayed enzymes have facilitated economical isolation, though it remains costlier than β-forms. These developments have sustained market growth, with current global capacity supporting a cyclodextrin industry valued at approximately 300 million USD annually, underscoring the causal link between biotechnological refinements and expanded commercial viability.

Applications

Pharmaceutical and Drug Delivery Uses

Cyclodextrins serve as pharmaceutical excipients primarily to enhance the aqueous , , and of poorly soluble s by forming non-covalent inclusion complexes, where the lipophilic is encapsulated within the hydrophobic cavity of the cyclodextrin . This host-guest interaction, driven by van der Waals forces and hydrogen bonding, has enabled their incorporation into diverse , including oral tablets, injectables, and ophthalmic solutions, with beta-cyclodextrin derivatives like hydroxypropyl-beta-cyclodextrin (HPβCD) being most prevalent due to superior and reduced compared to native beta-cyclodextrin. In parenteral formulations, sulfobutylether-beta-cyclodextrin (SBE-β-CD, marketed as Captisol) is FDA-approved for use in intravenous products, such as (Veklury) for treatment and (Kyprolis) for , where it solubilizes the active ingredient while maintaining low at doses up to 2 g per administration. HPβCD, similarly approved for parenteral, oral, and topical routes in the and , appears in products like itraconazole oral solution (Sporanox) to boost from less than 55% to over 90% in complexed form. , a modified gamma-cyclodextrin, encapsulates rocuronium to reverse neuromuscular blockade, with FDA approval in demonstrating rapid onset (under 2 minutes) and efficacy in over 95% of cases during recovery. For advanced drug delivery, cyclodextrins facilitate targeted systems such as nanoparticles and hydrogels; for instance, cross-linked beta-cyclodextrin nanoparticles have shown promise for anticancer drug loading, achieving controlled release via pH-sensitive degradation and up to 80% encapsulation efficiency for . In ocular delivery, HPβCD complexes with increase corneal penetration by 2-3 fold, reducing dosing frequency in treatments. Oral applications include taste-masking for bitter APIs like ibuprofen, where cyclodextrin inclusion reduces perceived bitterness by over 70% in pediatric formulations without altering dissolution profiles. Regulatory bodies recognize alpha-, beta-, and gamma-cyclodextrins as generally regarded as safe (GRAS) for pharmaceutical excipients, with derivatives like HPβCD limited to specific routes due to potential renal accumulation at high doses exceeding 16 g/day, though clinical data confirm safety in approved products with no significant or . Ongoing trials explore HPβCD as a therapeutic agent itself for Niemann-Pick type C by depleting lysosomal , with phase 3 data from 2022 showing slowed progression in pediatric patients at 2,000 mg/kg weekly infusions.

Food Industry and Nutraceutical Applications

Cyclodextrins (CDs), particularly α-, β-, and γ-CDs, serve as versatile excipients in the by forming host-guest inclusion complexes that encapsulate hydrophobic molecules, thereby enhancing their aqueous , , and controlled release. This mechanism relies on the CDs' toroidal , where the hydrophobic interior cavity traps guest molecules via non-covalent interactions, protecting them from oxidation, light, and heat degradation. In practice, β-CD is commonly used for flavor retention, achieving up to 79% preservation of odor during extrusion processing at concentrations of 1-4%. Similarly, CDs stabilize natural pigments like and , preventing color loss in products such as ginger extracts stored at 5°C for up to 4 weeks. Key applications include taste masking and bitterness reduction; for instance, 10% β-CD effectively diminishes the bitterness of milk casein hydrolysates by complexing bitter peptides. CDs also extend shelf life by mitigating lipid oxidation, as demonstrated by β-CD/limonene complexes retaining 40% of limonene after 10 days of exposure to air. In dairy processing, β-CD selectively sequesters cholesterol from milk fat, enabling low-cholesterol butter production without altering sensory attributes. Additionally, CDs remove undesirable contaminants like mycotoxins; 1% β-CD reduces patulin levels by 70% in apple juice via inclusion complexation. Solubility enhancement is evident in vanillin complexes with β-CD, which increase its water dispersibility for uniform flavor distribution in beverages. Regulatory approval supports these uses: α-, β-, and γ-CDs received (GRAS) status from the U.S. FDA in 2000, 2001, and 2004, respectively, for applications up to specified levels. In the , β-CD is authorized as E 459 with an (ADI) of 5 mg/kg body weight, primarily for stabilizing and solubilizing functions in categories like non-alcoholic beverages and . In formulations, CDs improve the and stability of bioactive compounds from natural sources, such as polyphenols and terpenoids, by overcoming their poor water and susceptibility to gastrointestinal degradation. Encapsulation with γ-CD, for example, boosts absorption by 18-fold in oral supplements through enhanced mucosal permeability. Curcumin-β-CD complexes demonstrate increased and efficacy , while resveratrol inclusion with hydroxypropyl-β-CD extends antioxidant activity in fortified foods like juices. Empirical data from studies show CDs protecting from against oxidation, yielding microcapsules with improved photostability and in models. These applications align with GRAS designations, facilitating CDs' integration into dietary supplements for targeted delivery of compounds like thymoquinone and .

Analytical and Industrial Techniques

Cyclodextrins serve as versatile agents in due to their ability to form host-guest inclusion complexes, facilitating selective molecular recognition, separation, and detection of analytes. In chromatographic techniques, cyclodextrin derivatives are incorporated into stationary phases or added to mobile phases to achieve high-resolution enantiomeric separations; for instance, β-cyclodextrin-bonded columns enable the resolution of chiral compounds in (HPLC) and (GC). Capillary electrophoresis (CE) employs cyclodextrins as chiral selectors, forming diastereomeric complexes that enhance separation efficiency, as demonstrated with analytes like dansyl-phenylalanine, allowing for portable, high-throughput analysis in devices such as the Mars Organic Analyzer. Spectroscopic applications leverage cyclodextrins to modulate analyte microenvironments, improving and signal intensity; this has enabled fluorescence-based detection of mycotoxins at concentrations as low as 25 parts per trillion by stabilizing excited states within the cyclodextrin cavity. utilize cyclodextrin-modified electrodes or sensors for enhanced selectivity in electrochemical detection, supporting applications in single-molecule analysis and through specific binding interactions. These techniques exploit both inclusion (analyte entering the hydrophobic cavity) and surface interaction modes, particularly in polar organic phases, providing advantages in sensitivity and reduced interference over traditional methods. In industrial processes, cyclodextrins are applied for encapsulation and stabilization in , where they form inclusion complexes with volatile fragrances like or , extending shelf life and enabling controlled release under thermal or mechanical stress. incorporates cyclodextrins via electrostatic adsorption or immobilization to create washable, non-adhesive aromatic nanocapsules on fabrics, achieving sustained fragrance delivery and improved eco-friendliness in flame-retardant formulations. Agricultural techniques use cyclodextrin complexes to encapsulate pesticides such as chloramidophos, enhancing their photostability and targeted release, thereby optimizing while minimizing off-target environmental exposure. These methods rely on the reversible nature of inclusion complexation, scalable through co-precipitation or processes for bulk production.

Environmental Remediation and Miscellaneous

Cyclodextrins facilitate primarily through host-guest inclusion complex formation, which enhances the and mobility of hydrophobic organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) in contaminated soils and water, enabling their extraction via washing processes or improved bioavailability for . In aged creosote-polluted soils, solutions of hydroxypropyl-β-cyclodextrin (HP-β-CD) and other derivatives have demonstrated extraction efficiencies for PAHs exceeding those of water alone, with specific studies reporting up to 50-70% removal of low-molecular-weight PAHs under optimized conditions. β-Cyclodextrin amendments have also boosted PAH and n-alkane uptake in setups using like Sedum alfredii, increasing pollutant concentrations in plant tissues by factors of 2-5 compared to controls. Functionalized cyclodextrins, such as those crosslinked or modified with polymers, serve as adsorbents for (e.g., lead, ) and pesticides in aqueous environments, achieving adsorption capacities of 100-300 mg/g for certain ions via and complexation, with regeneration possible through adjustments or solvent desorption for reuse in multiple cycles. Recent advancements include their use against per- and polyfluoroalkyl substances (PFAS), where cyclodextrin-based materials trap these persistent contaminants through hydrophobic cavity interactions, supporting sustainable . These applications leverage cyclodextrins' and low , though efficacy depends on derivative type, hydrophobicity, and matrix complexity, with peer-reviewed trials emphasizing the need for site-specific optimization over generalized deployment. In miscellaneous applications, cyclodextrins are incorporated into textiles for finishing treatments, where β-cyclodextrin onto fabrics enables controlled release of antimicrobials or odor-masking agents via inclusion complexes, improving against washing cycles by 20-50% in tested and substrates. In , they stabilize volatile fragrance compounds and active ingredients like retinoids by encapsulation, reducing evaporation losses by up to 80% and enhancing shelf-life in formulations such as creams and deodorants, as evidenced by phase solubility and DSC analyses confirming complex formation. Agricultural uses include enhancements, where cyclodextrins improve storage stability and targeted delivery, minimizing environmental leaching while maintaining efficacy against target pests. These non-core applications highlight cyclodextrins' versatility in material science, though remains constrained by production costs relative to synthetic alternatives.

Safety, Toxicology, and Regulatory Status

Human Health and Toxicity Data

Native α-, β-, and γ-cyclodextrins are classified as (GRAS) by the U.S. Food and Drug Administration () for oral use in food and pharmaceuticals, owing to their negligible systemic absorption following ingestion, with over 90% excreted unchanged in feces within 24 hours. Acute oral toxicity studies in report LD50 values exceeding 10 g/kg body weight, indicating low acute risk, though doses above 1000 mg/kg/day may induce reversible and cecal enlargement due to osmotic effects in the gut. Parenteral administration of unmodified β-cyclodextrin exhibits , characterized by renal tubular and crystal formation in preclinical models, attributed to its low water and accumulation in proximal tubules; this limits its intravenous use in humans, with solubility constraints preventing safe dosing above 0.1 mg/kg. In contrast, derivatives such as 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) demonstrate improved renal safety, with clinical trials for Niemann-Pick type C1 (NPC1) administering intravenous doses up to 2500 mg/m² weekly for up to 48 weeks, reporting primarily mild to moderate infusion-related reactions like and , without significant in patients without pre-existing renal impairment. However, long-term intrathecal HP-β-CD use in NPC1 trials has been associated with progressive , linked to cochlear damage via cholesterol depletion mechanisms, prompting dose adjustments and audiometric monitoring in protocols.31465-4/fulltext) Sulfobutylether-β-cyclodextrin (SBECD), used as a solubilizer in formulations like intravenous and , accumulates in renal impairment but shows no direct causation of in pharmacokinetic studies; post-marketing data from over 10,000 patients indicate reversible elevations in serum creatinine at doses up to 16 mg/kg, primarily due to interference rather than glomerular filtration decline. Certain methylated derivatives, such as heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB), are contraindicated for parenteral use due to hemolytic potential and renal observed in animal models and s. Overall, exposure data from approved uses affirm low systemic for oral and select parenteral forms, with risks primarily route- and derivative-dependent, supported by regulatory approvals from the FDA and for specific indications.

Environmental Fate and Impact

Cyclodextrins enter the environment primarily through industrial effluents, wastewater from pharmaceutical and , and agricultural applications involving remediation or formulations. Due to their high and cyclic , they exhibit limited volatility and to sediments, facilitating mobility in aqueous systems but also promoting microbial accessibility for degradation. In soil, cyclodextrins demonstrate biodegradability across various types, including α-, β-, and γ-cyclodextrins as well as derivatives like randomly methylated β-cyclodextrin (RAMEB) and hydroxypropyl-β-cyclodextrin (HPβCD). Laboratory and field studies in hydrocarbon-contaminated s with high and microbial activity showed depletion of even the more persistent RAMEB to approximately 40% of initial levels over two years under favorable aerobic conditions, indicating half-lives on the order of months to years depending on and microbial density. No evidence supports significant persistence or long-term accumulation in terrestrial compartments, as enzymatic by targets the glycosidic bonds, leading to complete mineralization to glucose and other innocuous products. Aquatic degradation follows similar microbial pathways, though rates may be slower in oligotrophic waters due to lower . Ecotoxicological assessments reveal low inherent , aligning with their use in to encapsulate persistent pollutants without secondary ecological harm. In aquatic systems, chronic exposure of hydroxypropyl-β-cyclodextrin at concentrations up to 1600 µg/L over 145 days in American (Jordanella floridae) produced no significant effects on adult , growth, or liver somatic index, though female gonadosomatic index increased slightly and second-generation larvae exhibited reduced growth and diminished tolerance to stress. Dextrin-based nanosponges incorporating cyclodextrins displayed mild to (Raphidocelis subcapitata) and cnidarians () at 1 mg/mL, but negligible impacts on (Artemia franciscana) and terrestrial seedling germination in pumpkin (), confirming ecosafety at environmentally relevant exposure levels. potential remains negligible owing to rapid , high molecular weight, and hydrophilicity, precluding in food webs. Overall, cyclodextrins pose minimal adverse impacts and may mitigate environmental contamination by enhancing pollutant for degradation.

Current Research and Future Directions

Recent Scientific Advances

Recent developments in cyclodextrin research have focused on enhancing precision through nanoscale systems and targeted formulations. In 2025, β-cyclodextrin-based multifunctional carriers were advanced for colon-targeted , demonstrating improved , controlled release, and reduced systemic in experimental models by leveraging host-guest interactions to encapsulate hydrophobic therapeutics. Similarly, cyclodextrin-in-liposome hybrids progressed for therapeutic applications, incorporating modified cyclodextrin derivatives with liposomal subtypes to achieve superior encapsulation efficiency and stability, as evidenced by and preclinical studies showing enhanced of entrapped agents. Biomedical material innovations include β-cyclodextrin-driven self-healing hydrogels, reported in August 2025, which exhibit reversible cross-linking via dynamic inclusion complexes, enabling applications in sustained drug release, , and with demonstrated and mechanical resilience in cellular assays. Cyclodextrins have also been integrated into theragnostic platforms for photothermal , where they stabilize nanoparticles for combined and tumor , with 2024-2025 studies confirming reduced off-target effects and improved photothermal conversion efficiency in murine models. Environmental applications saw a breakthrough in October 2025 with cyclodextrin-embedded membranes for sustainable water filtration, achieving approximately 75% removal of (from 11 mg/L initial concentration) through selective adsorption in lab tests, offering reusability after washing without performance degradation. In gene delivery, cyclodextrin polymers were refined in 2024 projects for non-viral vectors, improving efficiency and safety profiles by mitigating compared to viral alternatives, as validated in cellular and . These advances build on the 21st International Cyclodextrin Symposium in June 2024, which highlighted ongoing clinical evaluations of cyclodextrin-based formulations for inflammation-related diseases and bioactive complexes.

Potential Innovations and Challenges

Cyclodextrin derivatives are advancing through nanosponge architectures, which facilitate stimuli-responsive release of therapeutics such as anticancer agents, improving and site-specific in applications like . These innovations extend to multifunctional platforms incorporating cyclodextrins with or nanoparticles for enhanced cellular penetration and reduced off-target effects in and therapies. In environmental applications, cyclodextrin-based nanocomposites enable efficient adsorption of and organic pollutants from wastewater, achieving removal rates exceeding 90% in some β-cyclodextrin systems due to their hydrophobic cavities and . Further innovations include cyclodextrin-metal-organic frameworks for sustained release in agriculture and remediation, leveraging their structural versatility for encapsulating pesticides or nutrients with minimal leaching. Ultrasound-active cyclodextrin nanoparticles show promise for non-invasive imaging and therapy combinations, as demonstrated in synthesis methods enabling acoustic responsiveness. Key challenges encompass potential from high-dose or aggregated cyclodextrin polymers, necessitating expanded preclinical and clinical data to validate long-term safety. remains a barrier, with production costs and issues hindering commercialization of complex derivatives, alongside regulatory demands for proving inclusion complex stability under physiological conditions. In contexts, achieving uniform particle sizes and preventing premature guest release during storage or transit poses ongoing hurdles.

References

  1. https://pmc.ncbi.nlm.nih.gov/articles/PMC11050477/
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC11945013/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC7866268/
  4. https://www.sciencedirect.com/science/article/abs/pii/S0032959203002589
  5. https://pubmed.ncbi.nlm.nih.gov/2598927/
  6. https://chemiedidaktik.uni-wuppertal.de/fileadmin/Chemie/chemiedidaktik/disido/cyen/info/03_physical_cy.htm
  7. https://pubs.acs.org/doi/10.1021/acsomega.0c02760
  8. https://www.mdpi.com/1420-3049/30/14/3044
  9. https://www.sciencedirect.com/science/article/abs/pii/S0079670013001214
  10. http://www.thegoodscentscompany.com/data/rw1041811.html
  11. https://www.sciencedirect.com/topics/nursing-and-health-professions/cyclodextrin
  12. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9750405.htm
  13. https://www.mdpi.com/2673-4176/3/1/1
  14. https://www.sciencedirect.com/science/article/abs/pii/S0378517319305678
  15. https://www.nature.com/articles/srep35764
  16. https://pubchem.ncbi.nlm.nih.gov/compound/Alpha-Cyclodextrin
  17. https://pubchem.ncbi.nlm.nih.gov/compound/Gamma-Cyclodextrin
  18. https://pmc.ncbi.nlm.nih.gov/articles/PMC6099580/
  19. https://www.sciencedirect.com/science/article/pii/S2405844024159488
  20. https://pmc.ncbi.nlm.nih.gov/articles/PMC10459549/
  21. https://www.sciencedirect.com/science/article/pii/S0144861723009657
  22. https://pubmed.ncbi.nlm.nih.gov/2062811/
  23. https://www.jpharmsci.org/article/S0022-3549%2816%2941410-3/fulltext
  24. https://www.sigmaaldrich.com/US/en/product/sigma/h5784
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC7196545/
  26. https://www.sciencedirect.com/science/article/abs/pii/S0144861722012528
  27. https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.894386/full
  28. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/elps.201900134
  29. https://pubs.acs.org/doi/10.1021/acsomega.3c01950
  30. https://pmc.ncbi.nlm.nih.gov/articles/PMC7671212/
  31. https://www.mdpi.com/1420-3049/29/22/5319
  32. https://pubmed.ncbi.nlm.nih.gov/12226716/
  33. https://www.sciencedirect.com/science/article/pii/S0021925819534032
  34. https://pmc.ncbi.nlm.nih.gov/articles/PMC5015009/
  35. https://link.springer.com/article/10.1007/s00253-002-1057-x
  36. https://www.sciencedirect.com/science/article/pii/S0144861713007303
  37. https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2000.01031.x
  38. https://www.nature.com/articles/s41598-024-81490-z
  39. https://pubmed.ncbi.nlm.nih.gov/18600678/
  40. https://pubs.acs.org/doi/10.1021/cr970012b
  41. https://pmc.ncbi.nlm.nih.gov/articles/PMC8433980/
  42. https://pubs.acs.org/doi/10.1021/cr500081p
  43. https://chemiedidaktik.uni-wuppertal.de/fileadmin/Chemie/chemiedidaktik/disido/cyen/info/02_historical_cy.htm
  44. https://hal.science/hal-03259916v1/file/Morin-Crini-130yearsrevised.pdf
  45. https://www.sciencedirect.com/science/article/abs/pii/S0378517306009665
  46. https://cyclodextrinnews.com/2020/05/25/the-contribution-of-franz-schardinger-to-cyclodextrins/
  47. https://hal.science/hal-03259916/document
  48. https://www.alfachemic.com/cyclodextrin/history-of-cyclodextrin.html
  49. https://link.springer.com/chapter/10.1007/978-3-030-49308-0_1
  50. https://pubs.rsc.org/en/content/articlelanding/1997/jm/a605235e
  51. https://www.wacker.com/cms/en-us/products/product-groups/cyclodextrins-complexes/cyclodextrins-complexes.html
  52. https://www.scielo.br/j/cta/a/7kF8hBWc7rKZgPxpZCLLBdJ/?format=html&lang=en
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC10500893/
  54. https://www.kbvresearch.com/cyclodextrin-market/
  55. https://pubmed.ncbi.nlm.nih.gov/8897265/
  56. https://pmc.ncbi.nlm.nih.gov/articles/PMC2750546/
  57. https://www.sciencedirect.com/science/article/abs/pii/S0022354916414103
  58. https://www.captisol.com/
  59. https://www.sciencedirect.com/science/article/pii/S093964112200145X
  60. https://pubmed.ncbi.nlm.nih.gov/8923319/
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC6995511/
  62. https://pubs.acs.org/doi/10.1021/acsomega.4c10200
  63. https://pmc.ncbi.nlm.nih.gov/articles/PMC10574773/
  64. https://www.ema.europa.eu/en/documents/scientific-guideline/questions-and-answers-cyclodextrins-used-excipients-medicinal-products-human-use_en.pdf
  65. https://ift.onlinelibrary.wiley.com/doi/10.1111/1750-3841.17527
  66. https://www.alfachemic.com/cyclodextrin/regulatory-status-of-cyclodextrin.html
  67. https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2016.4628
  68. https://pmc.ncbi.nlm.nih.gov/articles/PMC10535610/
  69. https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.3288
  70. https://www.biosynth.com/blog/blog-series-3-applications-of-cyclodextrins-to-improve-the-stability-bioavailability-and-solubility-of-bioactive-compounds
  71. https://pubs.acs.org/doi/10.1021/ac400639y
  72. https://pubs.acs.org/doi/10.1021/cr970014w
  73. https://onlinelibrary.wiley.com/doi/abs/10.1002/rem.3440100206
  74. https://pmc.ncbi.nlm.nih.gov/articles/PMC7674206/
  75. https://www.sciencedirect.com/science/article/abs/pii/S0048969718342141
  76. https://www.researchgate.net/publication/236093775_Comparative_Effects_of_Several_Cyclodextrins_on_the_Extraction_of_PAHs_from_an_Aged_Contaminated_Soil
  77. https://www.tandfonline.com/doi/abs/10.1080/15226514.2024.2389563
  78. https://www.sciencedirect.com/science/article/pii/S002228602500016X
  79. https://link.springer.com/article/10.1007/s44274-024-00090-w
  80. https://link.springer.com/article/10.1007/s10311-025-01868-x
  81. https://pubmed.ncbi.nlm.nih.gov/34420160/
  82. https://pmc.ncbi.nlm.nih.gov/articles/PMC7465207/
  83. https://ris.utwente.nl/ws/files/6886338/Bhaskara11applications.pdf
  84. https://www.researchgate.net/publication/11320950_Applications_of_cyclodextrins_in_cosmetic_products_A_review
  85. https://www.sciencedirect.com/science/article/abs/pii/S0168365915302996
  86. https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00355/full
  87. https://pubmed.ncbi.nlm.nih.gov/15265610/
  88. https://dason.medicine.duke.edu/sites/dason.medicine.duke.edu/files/cyclodextrin_and_renal_function.pdf
  89. https://www.sciencedirect.com/science/article/abs/pii/S0278691511000950
  90. https://pubmed.ncbi.nlm.nih.gov/36279795/
  91. https://www.sciencedirect.com/science/article/pii/S2214426923000344
  92. https://pmc.ncbi.nlm.nih.gov/articles/PMC5676048/
  93. https://www.tandfonline.com/doi/full/10.1080/14740338.2021.1978976
  94. https://cyclodextrinnews.com/2024/02/27/renal-safety-of-sbecd/
  95. https://pubmed.ncbi.nlm.nih.gov/16018907/
  96. https://pubmed.ncbi.nlm.nih.gov/15993146/
  97. https://www.sciencedirect.com/science/article/abs/pii/S0045653505001396
  98. https://pubmed.ncbi.nlm.nih.gov/26467440/
  99. https://www.sciencedirect.com/science/article/pii/S0147651324001957
  100. https://cancer-nano.biomedcentral.com/articles/10.1186/s12645-025-00339-w
  101. https://www.sciencedirect.com/science/article/abs/pii/S0144861725013578
  102. https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202507227
  103. https://www.sciencedirect.com/science/article/abs/pii/S0144861725005764
  104. https://phys.org/news/2025-10-reusable-washable-nanofiber-membrane-filter.html
  105. https://www.carbohyde.com/2024/
  106. https://cyclodextrinnews.com/2025/01/02/end-of-year-statistics-2024/
  107. https://pmc.ncbi.nlm.nih.gov/articles/PMC11945956/
  108. https://www.researchgate.net/publication/380931311_Unleashing_the_potential_of_cyclodextrin-based_nanosponges_in_management_of_colon_cancer_A_review
  109. https://pmc.ncbi.nlm.nih.gov/articles/PMC12299055/
  110. https://www.sciencedirect.com/science/article/abs/pii/S0144861724012074
  111. https://pubs.acs.org/doi/abs/10.1021/acsanm.3c02026
  112. https://link.springer.com/article/10.1007/s10311-022-01509-7
  113. https://www.mdpi.com/1999-4923/16/8/1054
  114. https://www.sciencedirect.com/science/article/pii/S2590257125000203
  115. https://pmc.ncbi.nlm.nih.gov/articles/PMC11360519/
Add your contribution
Related Hubs
User Avatar
No comments yet.