Cyclodextrin Research Articles

Cyclodextrins and their potential applications for delivering vitamins, iron, and iodine for improving micronutrient status.

Cyclodextrins (CDs) have been investigated as potential biopolymeric carriers that can form inclusion complexes with numerous bioactive ingredients. The inclusion of micronutrients (e.g. vitamins or minerals) into cyclodextrins can enhance their solubility and provide oxidative or thermal stability. It also enables the formulation of products with extended shelf-life. The designed delivery systems with CDs and their inclusion complexes including electrospun nanofibers, emulsions, liposomes, and hydrogels, show potential in enhancing the solubility and oxidative stability of micronutrients while enabling their controlled and sustained release in applications including food packaging, fortified foods and dietary supplements. Nano or micrometer-sized delivery systems capable of controlling burst release and permeation, or moderating skin hydration have been reported, which can facilitate the formulation of several personal and skin care products for topical or transdermal delivery of micronutrients. This review highlights recent developments in the application of CDs for the delivery of micronutrients, i.e. vitamins, iron, and iodine, which play key roles in the human body, emphasizing their existing and potential applications in the food, pharmaceuticals, and cosmeceuticals industries.

Synthesis and characterization of a β-cyclodextrin-MOF-based porous hydrogel for efficient adsorption of Au3+, Ag+, and Pb2+ ions

Wastewater containing heavy metal ions produced by electroplating, smelting and other industries poses a threat to human safety. Recently, metal–organic frameworks (MOFs) have emerged as porous crystalline adsorbents for the removal of heavy metal ions. Starch-derived cyclodextrins (CDs), a series of cyclic oligosaccharides, have been explored for fabrication of cost-efficient MOF materials. However, the coordination bonds in CD-based MOFs can be destroyed by water, which limits their application as absorbent materials for the removal of heavy metal ions from wastewater. In this work, a β-CD-MOF-based porous hydrogel was developed by incorporating a crosslinked hydrogel network based on acrylic acid (AA) and N,N’-methylenebis(acrylamide) (MBA) monomers into a β-CD-based MOF structure. The synthesized porous hydrogel, denoted A/M−CDMOF−gel, not only showed enhanced structural stability but also exhibited excellent properties for simultaneous adsorption of Au3+, Ag+, and Pb2+ ions. A kinetic study revealed that the A/M−CDMOF−gel had a satisfactory binding rate within 60 min of contact, and the higher fit coefficient from the pseudo-second-order model indicated its chemical adsorption property. Moreover, according to the Langmuir isotherm model fitting results, the maximum capacity of the A/M−CDMOF−gel reached 316.4, 60.9, and 414.2 mg/g for Au3+, Ag+, and Pb2+, respectively. Therefore, the regenerable A/M−CDMOF−gel adsorbent is expected to provide ideas for the development of renewable absorbent materials in the field of wastewater treatment and remediation.

Exploring the bio-insecticidal activity of Eucalyptus globulus essential oil/β-cyclodextrin inclusion complexes: In vitro and in silico assessment against Ephestia kuehniella larvae

Owing to their beneficial functional capabilities, essential oils were largely used. However, their low aqueous solubility, instability, and high volatility urged scientists to their encapsulation with cyclodextrins (CDs) to tackle their shortcomings. In this study, the co-precipitation method was used to prepare β-CD/Eucalyptus globulus essential oil (EGEO) inclusion complexes (ICs). β-CD/EGEO ICs were prepared at ratios (w:w) 1:2 and 1:4 with an encapsulation efficiency of 93 and 96%, respectively. The ICs characterization using the Fourier transform Infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction, Dynamic Light Scattering, and Laser Doppler Velocimetry confirmed the formation of β-CD/EGEO ICs. The insecticidal activity of the free EGEO and ICs was explored and displayed that the complex β-CD/EGEO 1:4 had the highest activity with the lowest LC50 against Ephestia kuehniella larvae (5.03 ± 1.16 mg/g) when compared to the free oil (8.38 ± 1.95 mg/g). Molecular docking simulations stipulated that the compound α-Bisabolene epoxide had the best docking score (ΔG = −7.4 Kcal/mol) against the selected insecticidal target α-amylase. Additionally, toxicity evaluation of the studied essential oil suggested that it could be safely used as a potent bioinsecticide as compared to chemical insecticides. This study reveals that the formation of β-CD/EGEO ICs enhanced the oil activity and stability and could be a promising and safe tool to boost its application in food or pharmaceutical fields.

The influence of cyclodextrin on hydrophobicity of pipeline and asphalt distribution: A green and efficient corrosion inhibitor

Corrosion inhibitors face significant limitations due to their non-degradability and poor applicability to asphalt systems. The molecular simulation studies show that cyclodextrin (CD) and asphalt can form supramolecular corrosion inhibitors with pipeline hydrophobic modification and corrosion inhibition effects. In particular, the rich hydroxyl structure of CD enables it to stably bind to the pipeline by forming coordination bonds and feedback bonds. When 2 CD molecules are added, the initial wetting time of the emulsion is delayed by 257.81 % compared to Span 80 with the same mass fraction. When 4 CD molecules are added, the emulsion cannot wet the iron surface within the simulation time. Furthermore, the combination of CD and asphalt allows more than 90 % of the asphalt to emulsify and prevent the emulsion from spreading on the pipeline. This results in a synergistic corrosion inhibition effect. These findings suggest that CD-based supramolecular corrosion inhibitors have the potential to be effective and environmentally friendly alternatives to traditional inhibitors in asphalt systems.

Impact of the Position of the Hydroxyl Group in Monohydroxy Chalcones with 2-Hydroxypropyl-β-Cyclodextrin on Their Spectral, Biological, and Theoretical Properties

3-Hydroxychalcone (3HOCH) and 4-hydroxychalcone (4HOCH) compounds were synthesized from the reaction between acetophenone and either 3-hydroxybenzaldehyde or 4-hydroxy benzaldehyde, using KOH as a catalyst. Then the synthesized compounds were further reacted with two cyclodextrins (CDs) (2-hydroxypropyl-β-cyclodextrin and β-cyclodextrin), by a co-precipitation method to investigate their spectral (absorption, fluorescence, and Fourier transform infrared), biological, and theoretical properties. Two absorption maximums appeared at 307 and 253 nm for 3HOCH and 346 and 254 nm for 4HOCH in aqueous solution by absorption spectrophotometry. In the excited state, dual emission was observed at 362 nm and 426 nm for 3HOCH and 360 nm and 486 nm for 4HOCH in the same medium of H2O by fluorescence spectrophotometry. The apparent changes in the absorption and emission spectra were the result of the inclusion complex with a 1:1 molar stoichiometric ratio. The interaction of 3HOCH, 4HOCH, and the CDs in the solid state was characterized by Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction patterns (PXRD), scanning electron microscopy (SEM), antioxidant and antibacterial studies concerning the position of the hydroxyl (-OH) group at the m- or p-positions in chalcone. The optimized highest occupied molecular orbital (HOMO) diagram, lowest unoccupied molecular orbital (LUMO) diagram and molecular electrostatic potential (MEP) map for the isolated molecules and their inclusion complexes were done by Becke’s three-parameter (B3) hybrid functional method using the Lee-Yang-Parr (LYP) correlation levels of density functional theory (DFT) method with 3-21 G basis set.

Improving cyclodextrin yield via retarding retrogradation of debranched starches during the preparation of cyclodextrin with cyclodextrin glycosyltransferase and pullulanase

Improving substrate utilization is crucial for industrial conversion of starch. The introduction of pullulanase in cyclodextrin (CD) production has improved substrate utilization. However, complete utilization of debranched starches has not been achieved, mainly due to the retrogradation of debranched starches and the inhibitory effect of CDs on pullulanase during the catalytic reaction. This study aimed to establish an efficient CD preparation system by regulating the substrate concentration and reaction temperature. A Bacillus thermoleovorans pullulanase (BtPul) was selected for investigation of its interaction with CDs through inhibition pattern assays, fluorescence spectroscopy, and molecular docking. Results clarified that CDs inhibited BtPul, with α-CD showing the highest inhibition, followed by β-CD and γ-CD. γ-CD inhibited BtPul through a mixed mode of competitive and noncompetitive inhibition, while the other CDs inhibited BtPul competitively. When pullulan was used as the substrate, increasing the substrate concentration weakened the inhibitory effect of CDs to some degree, while changes in reaction temperature only had a minor contribution. When BtPul and β-CGTase collaboratively converted 30% (w/v) starch substrate, an increase in reaction temperature improved the conversion rate of β-CD from 67.6% to 86.8%. Optimization of substrate concentration showed that high concentration starch substrate had an adverse effect on CDs yield due to retrogradation. The optimal yields of α-CD and β-CD produced by BtPul and α-/β-CGTases were 55.7% and 90.3%, respectively. This study provides a reliable method and reference for the efficient conversion of starch into CDs.

Energy Transfer-Based Recognition of Membrane Cholesterol by Controlling Intradistance of Linker.

Gold nanoparticles (AuNPs) are good candidates for donor material in energy transfer systems and can easily be functionalized with various ligands on the surface with Au-S bonding. Cyclodextrin (CD) forms inclusion complexes with fluorophores due to its unique structure for host-guest interaction. In this study, we fabricated βCD-functionalized AuNPs using different lengths of thiol ligands and recognized cholesterol to confirm the energy-transfer-based turn-on fluorescence mechanism. AuNP-βCD conjugated with various thiol ligands and quenched the fluorescein (Fl) dye, forming βCD-Fl inclusion complexes. As the distance between AuNPs and βCD decreased, the quenching efficiency became higher. The quenched fluorescence was recovered when the cholesterol replaced the Fl because of the stronger binding affinity of the cholesterol with βCD. The efficiency of cholesterol recognition was also affected by the energy transfer effect because the shorter βCD ligand had a higher fluorescence recovery. Furthermore, we fabricated a liposome with cholesterol embedded in the lipid bilayer membrane to mimic the cholesterol coexisting with lipids in human serum. These cellular cholesterols accelerated the replacement of the Fl molecules, resulting in a fluorescence recovery higher than that of pure lipid. These discoveries are expected to give guidance towards cholesterol sensors or energy-transfer-based biosensors using AuNPs.

Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss.

Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss. Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model. Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure. Serum prestin levels were quantified using automated Western, and hair cell counts were obtained. All three doses induced an N -glycosylated ~134-kDa prestin burst; however, only the 3,000 and 4,000 mg/kg resulted in robust OHC loss. Prestin levels returned to baseline where they remained up to 15 weeks in the absence of OHCs. The ~134-kDa prestin burst induced after CDX administration is N -glycosylated, representing a posttranslational modification of prestin. Serum prestin seems to be a promising biomarker when using therapeutics with ototoxic properties because it is not dependent on OHC loss as a necessary event, thus affording the opportunity for early detection and intervention.

Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing

BackgroundSkin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds. RationaleIn this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. ResultsThe results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. ConclusionThis study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

The use of Cyclodextrin-SLS-PEG 4000 Complex to Solubilize Three BCS Class II and IV Drug´S through A Factorial Study Design

Objective: Drugs classified as Class II and IV on the Biopharmaceutical Classification System are commonly associated with solubility challenges. This research aims to investigate the impact of cyclodextrin combined with both PEG 4000 and SLS, individually and in combination, on the enhancement of solubility and dissolution rate of three drugs belonging to BCS Class II (celecoxib and Valsartan) and Class IV (Furosemide). Methods: A series of 23 factorial experiments were conducted to assess drug solubility in eight selected fluids containing Beta Cyclodextrin, Poly Ethylene Glycol 4000, Sodium Lauryl Sulphate, both separately and in binary and ternary combinations. Solid inclusion complexes of each drug with beta Cyclodextrin, PEG 4000 and SLS were prepared using the kneading method. The impact of each excipient on dissolution rates was evaluated through a23 factorial design. Results: The presence of the studied excipients significantly improved the solubility of the three drugs under investigation. Celecoxib solubility was highly enhanced by Cyclodextrin combined toPEG 4000 and SLS(2,77 ratio). Furosemide solubility was highly enhanced by Cyclodextrin combinedto SLS (ac) (2,96 ratio). And valsartan solubility by beta cyclodextrin combined to PEG 4000 and SLS(2,43 ratio). Among dissolution rates, the addition of PEG 4000 and SLS alongside Cyclodextrin led to even more substantial improvements: 14.96-ratio and 7.34-ratio enhancements, respectively on celecoxib dissolution rates, and 9,22-ratio and 11,73-ratio increases, respectively, for furosemide dissolution rates, then.2,09-ratio and 1,88-ratio, respectively on valsartan dissolution rates. Conclusion: Sodium Lauryl Sulphate demonstrates efficacy as a solubilizer both independently and in conjunction with ßCD and PEG 4000, effectively enhancing the solubility and dissolution rate of the selected BCS Class II and IV drugs.

Inclusion complex of ionic liquid 1-dodecylpyridinium tetrafluoroborate with sulfobutyl ether-β-cyclodextrin: Preparation and characterization

In this article an inclusion complex of hydrophobic ionic liquid 1-dodecylpyridinium tetrafluoroborate (PyrC12-BF4) and sodium salt of sulfobutyl ether β-cyclodextrin (SB-β-CD) has been synthesized and studied using NMR spectroscopy, UV–Vis spectroscopy, FT-IR, TGA, DSC and XRD. The results of 1H NMR study revealed physicochemical interactions between the hydrophobic alkyl chain of PyrC12-BF4 and protons of the inner cavity of SB-β-CD, as well as between the CH protons of pyridinium cation and the polar SB-β-CD groups. The formation of an inclusion complex has also been revealed by Wilhelmy plate method. The binding constant of the SB-β-CD/PyrC12-BF4 complex determined by the method of Higuchi and Connors was found to be 1210 M–1. According to DSC analysis data, only one endothermic peak is observed in the thermogram of the SB-β-CD/PyrC12-BF4 inclusion complex, thus confirming the formation of a new supramolecular system. Additional characterization methods such as thermal mass spectroscopy and TEM were also applied for characterization of the synthesized complex. Complexation of long-chain pyridinium salt with SB-β-CD can be an efficient approach for the preparation of new antimicrobial formulations with reduced toxicity.

Solubility and Dissolution Enhancement of Candesartan Cilexetil by Complexation with Cyclodextrin

At present, numerous novel chemical compounds face challenges related to their limited solubility in aqueous environments. These compounds are classified under the Biopharmaceutical Classification System (BCS) as either class II or class IV substances. Different carriers were used to increase their solubility. Candesartan cilexetil (CC) is one of the most widely used antihypertensive drugs, which belongs to class II drugs. The aim of this research was to enhance the solubility and dissolution rate of CC through a complexation approach involving β-cyclodextrin and its derivatives, specifically hydroxypropyl beta cyclodextrin (HP-β-CD), methyl beta cyclodextrin (M-β-CD), and sulfonyl ether beta-cyclodextrin (SBE-β-CD), serving as complexing agents. This complexation process was investigated both with and without the inclusion of poloxamer 407 (PX407) as a hydrophilic polymer. The complex was prepared through a combination of grinding, kneading, and co-evaporation techniques. The resulting complex underwent characterization, including assessments of its percentage yield, drug content, solubility, and dissolution properties, as well as analyses using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and fourier transforms infrared spectroscopy (FTIR). The results revealed that, the complex prepared using 1:1 molar ratio of M -β-CD:CC in the presence of 5% w/w PX407 by co-evaporation method had the highest percentage yield (97%) with drug content of 98.5%, the highest solubility (0.052 mg/mL) and fastest release of drug within 45 minutes compared to the other methods. The FTIR, DSC, and XRD confirmed the development of a partial inclusion complex of an amorphous nature

Auxiliary Substances for Enhancement of Complexation Efficiency and Dissolution Rate of Drug-Cyclodextrin Complexes

Background: Enzymatic starch breakdown yields 1, 4-linked D-glucopyranoside subunits, which are the building blocks of the cyclodextrin (CD) family of macromolecules. β-Cyclodetrins (β-CDs) have the capability to improve the solubility of partially soluble drugs, as well as their permeability across biological membranes and stability. However, factors like limited solubility, high cost of derivatives and their toxicity at high concentrations has directed the researchers toward multicomponent inclusion complexes (MCIC). Introduction: Incorporating auxiliary substances (AS) leads to MCIC formation during complexation. The auxiliary agent interacts at the molecular level with the CDs, enhances the complexation competence of β-CD or its derivatives, and minimizes the amount required for solubilization of poorly soluble drugs. They also enhance stability of drug-CD complex. Due to these advantages, the popularity of MCIC has increased amongst formulation scientists. Conclusion: This review describes various AS that could be used to prepare MCIC to expand solubility and other properties of drugs and minimize cost of related formulation.

Quorum quenching effect of cyclodextrins on the pyocyanin and pyoverdine production of Pseudomonas aeruginosa

Various virulence determinants in Pseudomonas aeruginosa are regulated by the quorum sensing (QS) network producing and releasing signalling molecules. Two of these virulence determinants are the pyocyanin and pyoverdine, which interfere with multiple cellular functions during infection. The application of QS-inhibiting agents, such as cyclodextrins (CDs), appears to be a promising approach. Further to method development, this research tested in large-volume test systems the effect of α- and β-CD (ACD, BCD) at 1, 5, and 10 mM concentrations on the production of pyocyanin in the P. aeruginosa model system. The concentration and time-dependent quorum quenching effect of native CDs and their derivatives on pyoverdine production was tested in a small-volume high-throughput system. In the large-volume system, both ACD and BCD significantly inhibited pyocyanin production, but ACD to a greater extent. 10 mM ACD resulted in 58% inhibition, while BCD only ~40%. Similarly, ACD was more effective in the inhibition of pyoverdine production; nevertheless, the results of RMANOVA demonstrated the significant efficiency of both ACD and BCD, as well as their derivatives. Both the contact time and the cyclodextrin treatments significantly influenced pyoverdine production. In this case, the inhibitory effect of ACD after 48 h at 12.5 mM was 57%, while the inhibitory effect of BCD and its derivatives was lower than 40%. The high-level significant inhibition of both pyocyanin and pyoverdine production by ACD was detectable. Consequently, the potential value of CDs as QS inhibitors and the antivirulence strategy should be considered.Keypoints• Applicability of a simplified method for quantification of pyocyanin production was demonstrated.• The cyclodextrins significantly affected the pyocyanin and pyoverdine production.• The native ACD exhibited the highest attenuation in pyoverdine production.

Cyclodextrin‐Based Catenanes Platformed with meso‐Arylporphyrin

AbstractAmong mechanically interlocked supramolecular systems with cyclodextrins (CDs), successful examples of CD‐based catenanes are limited compared to a number of CD rotaxanes owing to the synthetic difficulties. We herein demonstrate an efficient synthesis of a CD‐based catenane using a meso‐arylporphyrin (Por) platform. Using Por modified with two olefin‐terminated oxyethylene chains at the cis‐meso‐positions, an interlocked Por‐CD catenane was synthesized via olefin metathesis in the presence of per‐O‐methylated β‐CD (TMe‐β‐CD) in water. The novel Por‐CD catenane was obtained in 30 % isolated yield, which was characterized by MALDI‐TOF mass and NMR spectroscopies. In the latter part, we demonstrate determination of the binding constants between TMe‐β‐CD and meso‐(4‐sulfonatophenyl)porphyrin using Por‐CD catenane, 2,6‐di‐O‐methyl‐β‐CD (DMe‐β‐CD), and 13C‐labeled TMe‐β‐CD (13C‐TMe‐β‐CD). The host‐guest exchange reaction from the Por‐CD catenane/DMe‐β‐CD to the Por‐CD catenane/TMe‐β‐CD complexes was directly monitored through 1D HMQC spectroscopy. The ratio of these complexes revealed the difference in the binding affinities of DMe‐β‐CD and TMe‐β‐CD to Por. The stable 1 : 2 inclusion complex between meso‐tetrakis(4‐sulfonatophenyl)porphyrin (TPPS) and TMe‐β‐CD has been well‐studied for many years. This study is the first to determine the respective binding constants, K1 and K2, using the model system, to be 3.0×107 M−1 and 3.4×107 M−1, respectively.

Para-Phenylenediamine Dimer as a Redox-Active Guest for Supramolecular Systems.

Redox-active components are highly valuable in the construction of molecular devices. We combined two p-phenylenediamines (p-PDA) with a biphenyl (BiPhe) unit to prepare a supramolecular guest 4 consisting of three binding sites for cucurbit[7/8]uril (CBn) and/or cyclodextrins (CD). Supramolecular properties of 4 were investigated using NMR, UV-vis, mass spectrometry and isothermal titration calorimetry. Our analysis revealed that 4 forms higher-order host-guest complexes, wherein a CD unit occupies the central BiPhe site, secured by two CBn units at the terminal p-PDA sites. Additionally, 1 : 1 complexes with α-CD and β-CD, a 1 : 2 complex with γ-CD and 2 : 1 complexes with CB7 and CB8 were identified. Through UV-vis and cyclic voltammetry, redox processes leading to the formation of a stable, deep blue dication diradical of 4 are elucidated. Furthermore, it is demonstrated that CB7 selectively protects oxidised 4 from reduction in the presence of a reducing agent. The supramolecular and redox properties of the structural motif represented by 4 render it an interesting candidate for the construction of supramolecular devices.

Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics.

Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug-CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems.

Interaction of Cyclodextrins with Amphiphilic Alternating Cooligomers Possessing the Dense Triazole Backbone.

The interaction of cyclodextrins (CDs) with structure-controlled polymers is expected to provide significant insights into macromolecular recognition. However, the interaction of CDs with structure-controlled polymers has been an underexamined issue of investigation. Herein, alternating amphiphilic cooligomers (oligoCnAH, where n denotes the carbon number of alkyl groups; n = 4, 8, and 12) were synthesized by copper(I)-catalyzed azide-alkyne cycloaddition polymerization of heterodimers of 4-azido-5-hexynoic acid (AH) derivatives carrying N-alkylamide and t-butyl (tBu) ester side chains, followed by hydrolysis of the tBu ester, to study the interaction of CDs with oligoCnAH by 1H NMR, nuclear Overhauser effect spectroscopy, and pulse-field-gradient spin-echo NMR. These NMR studies indicated that αCD interacted with oligoC4AH, αCD and βCD interacted with oligoC8AH, and all CDs interacted with oligoC12AH. Based on the equilibrium models proposed, the binding constants were evaluated for the binary mixtures, which showed interaction. Comparing the interactions of the CDs/oligoC12AH binary mixtures with those of the binary mixtures of CDs and alternating copolymers of sodium maleate and dodecyl vinyl ether (polyC12M), it is concluded that oligoC12AH forms less stable micelles than does polyC12M presumably because of the lower molecular weight, the hydrophilic amide groups in the side chain, and the longer interval between neighboring C12 groups in oligoC12AH.

Enhancement of β-Cyclodextrin Production Using a Glycogen Debranching Enzyme from Saccharolobus solfataricus STB09.

Efficient production of cyclodextrins (CDs) has always been challenging. CDs are primarily produced from starch via cyclodextrin glycosyltransferase (CGTase), which acts on α-1,4 glucosidic bonds; however, α-1,6 glucosidic bonds in starch suppress the enzymatic production of CDs. In this study, a glycogen debranching enzyme from Saccharolobus solfataricus STB09 (SsGDE) was utilized to promote the production of β-CD by hydrolyzing α-1,6 glucosidic bonds. The addition of SsGDE (750 U/g of starch) at the liquefaction stage remarkably improved the β-CD yield, with a 43.9% increase. Further mechanism exploration revealed that SsGDE addition could hydrolyze specific branches with less generation of byproducts, thereby promoting CD production. The chain segments of a degree of polymerization ≥13 produced by SsGDE debranching could also be utilized by β-CGTase to convert into CDs. Overall, these findings proposed a new approach of combining SsGDE with β-CGTase to enhance the CD yield.

CYCLODEXTRIN IN NOVEL FORMULATIONS AND SOLUBILITY ENHANCEMENT TECHNIQUES: A REVIEW

Using cyclodextrin helps make different dosage forms more soluble. The oligosaccharide class known as cyclodextrins (CDs) is made up of glucose units bound together in a ring. CDs have the promising ability to assemble into complexes with drug molecules and improve their physicochemical properties without the need for molecular modifications. Generally, drug-CD complexes have a stoichiometry of 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media, which can reduce the solubility of the CDs by aggregating. One can increase their complexation capacity and solubility through derivative formation, but the final outcome depends on the kind and extent of substitution. Drug penetration through biological membranes can be improved by the formation of water-soluble drug-CD complexes. Solubility is the property of a solid dissolving into a liquid phase to form a homogenous system. Solubility is a crucial component in obtaining the right drug concentration in the systemic circulation for the optimal pharmacological response. Orally administered poorly soluble drugs often require high dosages to reach therapeutic plasma concentrations. Their low solubility in water is one of the primary problems with creating new chemical entities through formulation. The BCS classification system places these medications in class II, which is characterized by high permeability and poor solubility. To greatly improve these medications, it is possible to make them more bioavailable and soluble.