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In this research work, the binding mechanism of Bisoprolol (BIS) drug into the beta‐cyclodextrin (β‐CD) and gamma‐cyclodextrin (γ‐CD) nanopores were investigated using docking, molecular dynamics (MD) simulations, and MM‐PBSA free energy calculations. Also, we assessed the energetic aspects within the BIS‐CDs complex under different thermal conditions in four stages from 298 to 334 K, which includes mammalian body temperature in order to approximate physiological conditions. The computational results reveal that the encapsulation of the BIS into the cavities of CDs is reinforced by hydrogen bonds (HBs) and van der Waals (vdW) interactions in the aqueous phase. The stability of the inclusion complexes of β and γ‐CD with BIS was confirmed by evaluating system stability, flexibility, dynamic and thermodynamic properties at all temperature steps. Next, we analyzed the degree of complexation between BIS and CDs at four different temperatures. The findings revealed that the degree of complexation is decreased as the temperature is increased. The translational movement of the drug to the outside of the CDs cavity increased in the temperature range of 310 to 334 K in γ‐CD more than β‐CD. The β‐CD complex exhibits greater stability compared to the γ‐CD complex in the aqueous medium. The MM‐PBSA free energy approach also confirms more binding affinity of BIS drug into the β‐CD cavity. keywords: Bisoprolol, β‐cyclodextrin, γ‐cyclodextrin, Molecular dynamics, MM‐PBSA free energy. [ABSTRACT FROM AUTHOR]

Background: Encapsulation of siRNA fragments inside liposome vesicles has emerged as an effective method for delivering siRNAs in vitro and in vivo. However, the liposome's fluid-phospholipid bilayer of liposomes allows siRNA fragments to diffuse out of the liposome, decreasing the dose concentration and therefore the effectiveness of the carrier. We have previously reported that β-cyclodextrins formulated in liposomes help increase the stability of siRNAs in cell culture medium. Here, we continued that study to include α, γ, methyl-β-cyclodextrins and β-cyclodextrin-modified gold and selenium nanoparticles. Methods: We used Isothermal Titration Calorimetry to study the binding thermodynamics of siRNAs to the cyclodextrin-modified nanoparticles and to screen for the best adamantane derivative to modify the siRNA fragments, and we used gel electrophoresis to study the stabilization effect of siRNA by cyclodextrins and the nanoparticles. Results: We found that only β- and methyl-β-cyclodextrins increased siRNA serum stability. Cyclodextrin-modified selenium nanoparticles also stabilize siRNA fragments in serum, and siRNAs chemically modified with an adamantane moiety (which forms inclusion complexes with the cyclodextrin-modified-nanoparticles) show a strong stabilization effect. Conclusions: β-cyclodextrins are good additives to stabilize siRNA in cell culture medium, and the thermodynamic data we generated of the interaction between cyclodextrins and adamantane analogs (widely used in drug delivery studies), should serve as a guide for future studies where cyclodextrins are sought for the delivery and solvation of small organic molecules. [ABSTRACT FROM AUTHOR]

In the present report, we have described the synthesis of N-aminopolyhydroquinoline (N-PHQ) derivatives using highly efficient β-cyclodextrin (β-CD) as a catalyst by the Hantzsch condensation of substituted aromatic aldehydes, dimedone, and hydrazine hydrate in one pot. The reactions were completed in a shorter time without the generation of any other byproduct. The synthesized N-PHQs were washed thoroughly with distilled water and recrystallized with ethanol to get highly purified products (as crystals). The structure of the synthesized N-PHQs was established by using advanced spectroscopic techniques like FT-IR, NMR (1H, 13C, DEPT, COSY, and HSQC), ESI-MS, and Elemental Analyzer. The N-PHQs derivatives demonstrated moderate to excellent resistance against the tested strains (both fungal as well as bacterial). The presence of polar groups, which are able to form H-bonds, attached to the phenyl ring like -NO2 (4b and 4c), and -OMe (4i, 4j, and 4k) exhibits excellent activity, which is comparable to standard drugs, amoxicillin and fluconazole. [ABSTRACT FROM AUTHOR]

Folic acid (FA) and its structural analog, anticancer medicine methotrexate (MTX), are known to form host/guest complexes with native cyclodextrins, of which the most stable are formed with the medium-sized β-cyclodextrin. Based on our research, proving that simple sugars (D-glucose, D-galactose, and D-mannose) can form adducts with folic acid, we envisioned that combining these two types of molecular receptors (cyclodextrin and simple carbohydrates) into one may be beneficial for the complexation of FA and MTX. We designed and obtained host/guest inclusion complexes of FA and MTX with two monoderivatives of β-cyclodextrin—substituted at position 6 with monosaccharide (glucose, G-β-CD) and disaccharide (maltose, Ma-β-CD). The complexation was proved by experimental (NMR, UV-vis, IR, TG, DSC) and theoretical methods. We proved that derivatization of β-cyclodextrin with glucose and maltose has a significant impact on the complexation with FA and MTX, as the addition of one glucose subunit to the structure of the receptor significantly increases the value of association constant for both FA/G-β-CD and MTX/G-β-CD, while further extending a pendant chain (incorporation of maltose subunit) results in no additional changes. [ABSTRACT FROM AUTHOR]

Ceramide 2 is the main lipid of stratum corneum and a popular component in skin healthcare products. But developing ceramide 2 based corneal protecting product is troublesome due to its insoluble feature in water. In this work, a novel type of inclusion nanoparticle was developed to solubilize and enhance the corneal repair effect of ceramide 2 by the anti-solvent method. It was revealed that the types of solvents and cyclodextrins influenced the precipitation rate as well as the stability of intermediate clusters of ceramide 2, where DMSO with moderate supersaturation promoted the formation of inclusion complex with β-cyclodextrins. The ceramide-cyclodextrin inclusion complex had an amphiphilic structure, which could self-assemble into nanoparticles in water, as evidenced by disappeared endothermic peaks of ceramide (78°C) and cyclodextrin (120°C), as well as appearance of two endothermic peaks corresponding to nanoparticle transition (45°C) and dissociation of cyclodextrin inclusion complex (102°C). Upon treating rat damaged skins with ceramide 2 inclusion nanoparticles, the cumulative permeation of indomethacin (IND, a model drug for skin permeability) were found to be 330.80 ± 54.86 μg/cm2, which was significantly lower than the control group (472.47 ± 154.83 μg/cm2). In comparison, water suspensions of ceramide 2 showed no corneal repair effect. [ABSTRACT FROM AUTHOR]

Pyridines and its derivatives are an important class of heterocyclic compounds of low molecular weight. They have been used in the treatment of a various diseases like cardiovascular disease, antioxidant, antibacterial, anti-tubercular, anticancer, anticoagulant, etc. In 1882, Arthur Hantzsch reported pyridine derivative synthesis using different aldehydes, 2 molecules β-keto ester and ammonium acetate to give a Hantzsch ester or 1,4-dihydropyridine derivatives. This review article focuses on different protocols for Hantzsch reaction using different catalysts like β-cyclodextrin–polyurethane polymer (β-CDPU), chitosan nanoparticles (NPs), salicylic acid, p-toluenesulfonic acid (p-TSA), alginic acid, Fe-TUD-1, PdRuNi@GO, Ceric Ammonium Nitrate (CAN), sulfate polyborate, etc. for the synthesis of pyridine derivatives. [ABSTRACT FROM AUTHOR]

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal–organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems. [ABSTRACT FROM AUTHOR]

As a critical cause of human dysfunctionality, hepatic failure leads to approximately two million deaths per year and is on the rise. Considering multiple inflammatory, oxidative, and apoptotic mechanisms behind hepatotoxicity, it urges the need for finding novel multi-targeting agents. Curcumin is a phenolic compound with anti-inflammatory, antioxidant, and anti-apoptotic roles. Curcumin possesses auspicious health benefits and protects against several diseases with exceptional safety and tolerability. This review focused on the hepatoprotective mechanisms of curcumin. The need to develop novel delivery systems of curcumin (e.g., nanoparticles, self-micro emulsifying, lipid-based colloids, solid lipid nanoparticles, cyclodextrin inclusion, phospholipid complexes, and nanoemulsions) is also considered. [ABSTRACT FROM AUTHOR]

This study evaluates the antiproliferative potential of flavanones, chromanones and their spiro-1-pyrazoline derivatives as well as their inclusion complexes. The main goal was to determine the biological basis of molecular pro-apoptotic activities and the participation of reactive oxygen species (ROS) in shaping the cytotoxic properties of the tested conjugates. For this purpose, changes in mitochondrial potential and the necrotic/apoptotic cell fraction were analyzed. Testing with specific fluorescent probes found that ROS generation had a significant contribution to the biological anticancer activity of complexes of flavanone analogues. TT (thrombin time), PT (prothrombin time) and APTT (activated partial tromboplastin time) were used to evaluate the influence of the compounds on the extrinsic and intrinsic coagulation pathway. Hemolysis assays and microscopy studies were conducted to determine the effect of the compounds on RBCs. [ABSTRACT FROM AUTHOR]

In the present study, a drug-delivery system based on electrospun nanofiber was developed. Polyamide (PA) as a fibers matrix was employed for the delivery of the anticancer drug doxorubicin (DOX). The nanofiber (NFs) was initially modified by incorporating β-cyclodextrin (β-CD) to generate an inclusion complex of β-CD and drug. The modified nanofiber was subsequently fabricated via an electrospinning approach of DOX/β-CD-incorporated PA. For understanding the role of β-CD in the inclusion of DOX, a DOX-incorporated nanofiber (i.e., PA/β-CD) was fabricated for comparison. β-CD enhanced the loading of DOX into PA NFs, resulting in an increased loading efficiency of 56% (PA/β-CD/DOX), compared to 47% for PA/DOX. In addition, the release profile of DOX and the effect of β-CD on the release behavior were investigated. The results demonstrated a substantial release of the drug (total release = ~ 92%) from PA/β-CD/DOX NFs, with a slower release rate (within 4 days) compared to PA/DOX without β-CD (total release = ~ 77%). Consequently, β-CD played a significant role in the sustained release of the drug. The viability of prostate cancer and LNCap cells in response to the drug was assessed for the NFs. The decreased cell viability observed in PA/β-CD/DOX indicates a sustained and controlled release behavior for this drug carrier system. [ABSTRACT FROM AUTHOR]

This study investigates the optimization of submerged culture conditions for the production of extracellular cyclodextrin glucanotransferase (CGTase) enzyme by Bacillus macerans ATCC 8244, employing Taguchi orthogonal array (OA) experimental design methodology. Five critical factors - starch, peptone, temperature, pH, and agitation speed - were examined at two levels using an OA layout of L8 for the experimental design. Analysis revealed a significant enhancement in CGTase yield, with the modified culture conditions resulting in a 21.2% increase from 513.416 U/ml to 622.5 U/ml. The successful application of Taguchi's design methodology underscores its efficacy in optimizing enzyme production processes. This study highlights Taguchi's design potential as a valuable tool for improving CGTase production efficiency while minimizing resource consumption. Additionally, the utilization of a packed bed bioreactor (PBR) facilitated continuous production of β-cyclodextrin (β-CD), demonstrating stability over 10 days with only a slight decrease in productivity. The K m,app value was determined to be 23.4 mg starch/ml, indicating a slight increase. [Display omitted] • Taguchi design optimizes enzyme production and Enhanced CGTase yield by 21.2%. • PBR enables continuous β-CD production and Thermal stability observed over 10 days. • The K m,app value was determined to be 23.4 mg starch/ml. [ABSTRACT FROM AUTHOR]

We describe the synthesis and characterization of a hydroxylated aza-adamantyl nitroxide radical Z-3, with the solubility in water of 170 mM at room temperature. We find that hydroxylation has no significant effect on the electronic structure and stability of aza-adamantyl nitroxides. We prepare a series of β-cyclodextrin (β-CD) derivatives which can form stoichiometric 1 : 1 inclusion complexes with Z-3, to investigate their effects on water solubility and stability of the radical upon complexation. The results indicate that water solubility of Z-3 increases by 1.4–3 times, while the radical stability somewhat decreases, depending on different β-CD substituents. Overall, sodium disulfobutylether-β-CD shows the best result in complexation with Z-3, providing water solubility >0.35 mol L−1, while maintaining the stability of the nitroxide radical with a half-life of 13.5 days at room temperature in water. [ABSTRACT FROM AUTHOR]

Boswellia carterii (BC) resins plants have a long historical background as a treatment for inflammation, as indicated by information originating from multiple countries. Twenty-seven diterpenoids have been identified in ethyl acetate and total methanol BC, comprising seventeen boscartins of the cembrane-type diterpenoids and ten boscartols of the prenylaromadendrane-type diterpenoids. Moreover, twenty-one known triterpenoids have also been found, encompassing nine tirucallane-type, six ursane-type, four oleanane-type, and two lupane-type. The cembrane-type diterpenoids hold a significant position in pharmaceutical chemistry and related industries due to their captivating biological characteristics and promising pharmacological potentials. Extraction of BC, creation and assessment of nano sponges loaded with either B. carterii plant extract or DEX, are the subjects of our current investigation. With the use of ultrasound-assisted synthesis, nano sponges were produced. The entrapment efficiency (EE%) of medications in nano sponges was examined using spectrophotometry. Nano sponges were characterized using a number of methods. Within nano sponges, the EE% of medicines varied between 98.52 ± 0.07 and 99.64 ± 1.40%. The nano sponges' particle sizes varied from 105.9 ± 15.9 to 166.8 ± 26.3 nm. Drugs released from nano sponges using the Korsmeyer-Peppas concept. In respiratory distressed rats, the effects of BC plant extract, DEX salt and their nano formulations (D1, D5, P1 and P1), were tested. Treatment significantly reduced ICAM-1, LTB4, and ILβ 4 levels and improved histopathologic profiles, when compared to the positive control group. Boswellia extract and its nano sponge formulation P1 showed promising therapeutic effects. The effect of P1 may be due to synergism between both the extract and the formulation. This effect was achieved by blocking both ICAM-1 and LTB4 pathways, therefore counteracting the effects of talc powder. [ABSTRACT FROM AUTHOR]

The relationship between the membrane-disrupting antibacterial activities and the structures of cyclodextrin derivatives containing cationic and hydrophobic moieties was investigated. [ABSTRACT FROM AUTHOR]

This study investigates unexpected competitive host–guest interactions of β‐cyclodextrin (β‐CD), which can occur with polymers in aqueous solution, using the examples of the two polymers poly(oligo(ethylene glycol) methyl ether methacrylate) and poly(glycerol mono methacrylate). Systematic structural modifications of the polymer provide insight into the host–guest interaction with β‐CD and the competition between side chains and end groups such as hydrophobic end groups remaining from reversible addition fragmentation chain transfer polymerization or intentionally implemented molecular recognition units such as arylazopyrazole photoswitches. [ABSTRACT FROM AUTHOR]

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: −30.1% iNO, −22.1% SIN-1A-5, −31.2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability. [ABSTRACT FROM AUTHOR]

A zinc phosphate/hydroxyapatite composite (ZP/HAP) with a core–shell nano-rod morphology and its functionalized derivative with β-cyclodextrin (β-CD) were evaluated as potential carriers of the drug cisplatin (CPN). The developed CD@ZP/HAP displayed remarkably enhanced CPN loading properties (375.8 mg g−1) compared to ZP/HAP (259.8 mg g−1). The CPN loading behavior of CD@ZP/HAP followed Langmuir isotherm properties (R2 > 0.99) and the kinetic activities of the pseudo-first-order model (R2 > 0.97). The steric assessment validated the notable increase in existing loading receptors after the functionalization of ZP/HAP with β-CD from 57.7 mg g−1 (ZP/HAP) to 72.3 mg g−1. Functionalization also affected the capacity of each receptor, ensuring that there were six CPN molecules (CD@ZP/HAP) instead of five (ZP/HAP), as well as the loading energies (<40 kJ mol−1), the loading of CPN by physical multi-molecular processes, and the vertical orientation. The CPN release patterns of CD@ZP/HAP exhibited slow and controlled properties (94.5% after 200 h at pH 7.4, and 100% after 160 h at pH 5.5), which were faster than those of ZP/HAP. The kinetic modeling of the release activities and diffusion exponent (>0.45) reflected the release of CPN according to both erosion and diffusion mechanisms. The loading of CPN into both ZP/HAP and CD@ZP/HAP also resulted in a marked enhancement in the anticancer activity of CPN against human cervical epithelial malignancies (HeLa) (cell viability = 5.6% (CPN), 3.7% (CPN loaded ZP/HA), and 1.8% (CPN loaded CD@ZP/HAP)). [ABSTRACT FROM AUTHOR]

Eugenol–β‐cyclodextrin complex has been widely used because of the enhanced stability and conservation of the properties of eugenol. Applications in food and health sciences have been shown previously, which makes this complex an excellent model to understand and develop methodologies for the analysis and prediction of physical properties. In this work, the dynamics of eugenol incorporated into β‐cyclodextrin are presented, using NMR relaxation rates, and the predictive capabilities of molecular dynamics simulations are discussed. Results show a hindered rotation of eugenol around the principal inertial axes when located inside β‐cyclodextrin. Moreover, a translational movement of the whole complex is demonstrated. [ABSTRACT FROM AUTHOR]

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl β-cyclodextrin (HPβCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPβCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPβCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of 5-amino-1H-pyrazole-4-carbonitriles using Ag/ZnO nanoparticles as a recyclable catalyst. The authors developed a one-pot procedure using environmentally friendly plant extracts to prepare the nanoparticles and optimized the reaction conditions to achieve high yields. The protocol proved to be effective for the synthesis of the desired compounds, which have various biological activities and are found in important drugs. The document also provides spectroscopic data for the synthesized compounds and acknowledges the institutions for support. [Extracted from the article]

Carboxymethyl cellulose and β-cyclodextrin stabilized water-wrapped tea seed oil Pickering emulsion was prepared using the high-speed shearing method. The particle size test and microstructure observation showed that the average particle size of the emulsion droplet decreased while the apparent viscosity, viscoelasticity, and stability increased with the increase in the concentration of carboxymethyl cellulose, β-cyclodextrin, and oil fraction. The droplet size of the emulsion increased slightly after heating from 50 °C to 90 °C, and the thermal stability of the emulsion increased after 50 °C treatment. pH exhibited little effect on emulsion stability. Carboxymethyl cellulose enhanced the adsorption of cyclodextrin colloidal particles on the water-oil interface via non-covalent interaction, steric hindrance, and drainage, which improved the viscosity of the emulsion. Therefore, it can be seen that the combination of carboxymethyl cellulose and β-cyclodextrin can significantly increased the stability of emulsions. [ABSTRACT FROM AUTHOR]

Nanofilms that can fast permeate solvents and accurately sieve molecules are of significant importance for separation. A promising strategy is to align the inner cavities of macrocycles into the channels within nanofilms, and control the channel size by selecting the macrocycles. However, the channels outside the macrocycles are ignored. Here, we prepare nanofilms with hydrophobic channels (cyclodextrin inner cavity) and hydrophilic channels (cyclodextrin outer space) through interfacial polymerization of azobenzene-4,4′-dicarbonyl dichloride and amino-functionalized β-cyclodextrin. By utilizing the significant geometric changes caused by the photoisomerization of azobenzene, nanofilms with adjustable hydrophilic channel sizes were obtained. Our nanofilms have high permeability to polar and non-polar solvents, and can distinguish molecules with almost the same molecular weight but different shapes. This work expands the development of next-generation nanofilms generated through interfacial polymerization by incorporating rational molecular design. [ABSTRACT FROM AUTHOR]

Atenolol (ATE) and propranolol (PRO) inclusion complexes with β-cyclodextrin have been investigated in aqueous solution. The aqueous solution was examined and characterized using UV–vis, fluorescence spectroscopy, and 1H NMR. The physical mixture was characterized using FTIR. The existence of inclusion complexes is confirmed by observing changes in spectroscopic properties. The ATE complex with β-CD exhibited an interaction as host and (β-CD) as a guest in a 1:1 ratio, with an inclusion constant K of 2.09 × 10−3 µM−1, as determined by the typical double-reciprocal graphs. Similarly, the PRO complex with β-CD exhibited an interaction as host and (β-CD) guest in 1:1 and 1:2 stoichiometry at the same time; the inclusion constants were K1 = 5.80 × 10−5 µM−1 and K2 = 4.67 × 10−8 µM−1, as determined by typical double-reciprocal graphs. The variables influencing the formation of the inclusion complexes were investigated and optimized. Based on the enhancement in fluorescence intensity due to the formation of inclusion complexes, spectrofluorometric methods were developed and validated for determination of each drug's pharmaceutical formulation. The quantification of the fluorescence intensity for ATE and PRO was conducted at λex/λem 226/302 nm and λex/λem 231/338 nm, respectively. Under the optimal reaction circumstances, linear relationships with good correlation coefficients of 0.9918 and 0.99 were found in the concentration ranges of 0.3–1.7 μM, and 0.1–1.1 μM for ATE and PRO, respectively. The limits of detection (LODs) were found to be 0.13 and 0.01 μM for ATE and PRO, respectively. The suggested approach was effectively applied to the analysis of both drugs' pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Lipoic acid trisulfide, a sulfane sulfur-containing trisulfide of α-lipoic acid, holds promise in pharmaceuticals, yet knowledge gaps persist regarding its synthesis, properties, and stability. Here, we synthesized the lipoic acid trisulfide with a purity exceeding 99% from α -lipoic acid on a gram scale and obtained novel β - cyclodextrin clathrates (84%-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in β-cyclodextrins. The resulting β-cyclodextrin clathrates exhibited significant improvements in water solubility and thermal stability. This pioneering study demonstrated a novel approach to the practical preparation of trisulfide and its β-cyclodextrin clathrates as active ingredients, paving the way for clinical development. [ABSTRACT FROM AUTHOR]

Riluzole (RLZ), a sodium channel-blocking benzothiazole anticonvulsant BCS class II drug, is very slightly soluble in aqueous medium. To improve aqueous solubility and modulate dissolution rate and membrane permeability, complex formation of RLZ with two cyclodextrin, α-cyclodextrin (α-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD), was studied. The stability constants demonstrated a greater affinity of SBE-β-CD towards RLZ compared to α-CD. A solubility growth of 1.7-fold and 3.7-fold with α-CD and SBE-β-CD, respectively, was detected in the solutions of 1% cyclodextrins and accompanied by the permeability reduction. For 1% CD solutions, several biopolymers (1% w/v) were tested for the membrane permeability under static conditions. The synergistic positive effect of α-CD and polymer on the solubility accompanied by unchanged permeability was revealed in RLZ/α-CD/PG, RLZ/α-CD/PEG400, and RLZ/α-CD/PEG1000 systems. Solid RLZ/CD complexes were prepared. Dynamic dissolution/permeation experiments for the solid samples disclosed the characteristic features of the release processes and permeation rate through different artificial membranes. The maximal permeation rate was determined across the hydrophilic semi-permeable cellulose membrane followed by the lipophilic PermeaPad barrier (model of intestinal and buccal absorption) and polydimethylsiloxane-polycarbonate membrane (simulating transdermal delivery way). Different mode of the permeation between the membranes was estimated and discussed. [ABSTRACT FROM AUTHOR]

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with β-cyclodextrin (βCD) and hydroxy propyl β-cyclodextrin (HPβCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with βCD and HPβCD. This study identified the most soluble complex (ALB–HPβCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB–HPβCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB–HPβCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration. [ABSTRACT FROM AUTHOR]

A selective amperometric sensor was developed to detect the antibiotic ceftriaxone (CEF) using a composite film of poly(β‐cyclodextrin) and a metal‐organic framework (MOF). The sensor was obtained by electro‐polymerizing β‐cyclodextrin (β‐CD) onto a glassy carbon electrode (GCE) previously coated with a MIL‐101(Cr) MOF film. This design prevents MOF particles' loss during extended electrode use. The MOF was structurally characterized using scanning electron microscopy, X‐ray diffraction, N2 adsorption‐desorption isotherms (BET method) and FTIR spectroscopy. Electrochemical impedance spectroscopy and cyclic voltammetry were used to assess the GCE/MIL‐101(Cr)‐pβ‐CD sensor, revealing reduced charge transfer resistance and enhanced sensitivity to CEF. Differential pulse voltammetry was then employed for CEF determination. Under optimized conditions, the sensor exhibited high sensitivity, a broad linear working range of 0.5 to 6 μM (R2=0.991), and a low detection limit of 0.34±0.02 μM (0.19±0.01 mg L−1). The selectivity of the sensor was evaluated in the presence of potential interferences such as organic acids, antibiotics and selected ions expected to affect the CEF signal. In an application to quantify a pharmaceutical formulation, the sensor displayed an impressive recovery rate of 98.3 % compared to results obtained using high‐performance liquid chromatography. [ABSTRACT FROM AUTHOR]

Abstract Cyclodextrins (CDs) can enhance the stability and bioavailability of pharmaceutical compounds by encapsulating them within their cavities. This study utilized molecular dynamics simulations to investigate the interaction mechanisms between hydrocortisone (HC) and various methylated CD derivatives. The results reveal that the loading of HC into CD cavities follows different mechanisms depending on the degree and position of methylation. Loading into βCD and 6-MeβCD was more complete, with the hydroxyl groups of HC facing the primary hydroxyl rim (PHR) and the ketone side facing the secondary hydroxyl rim (SHR). In contrast, 2,3-D-MeβCD and 2,6-D-MeβCD showed a different loading mechanism, with the ketone side facing the PHR and the hydroxyl groups facing the SHR. The root mean square fluctuation (RMSF) analysis demonstrated that methylation increases the flexibility of CD heavy atoms, with 3-MeβCD and 2,3-D-MeβCD exhibiting the highest flexibility. However, upon inclusion of HC, 3-MeβCD, 2,3-D-MeβCD, 2-MeβCD, and 6-MeβCD showed a significant reduction in flexibility, suggesting a more rigid structure that effectively retains HC within their cavities. The radial distribution function revealed a significant reduction in the number of water molecules within the innermost layer of the methylated CD cavities, particularly in TMeβCD, indicating a decrease in polarity. The presence of HC led to the release of high-energy water molecules, creating more favorable conditions for HC loading. Conformational analysis showed that methylation caused a partial decrease in the area of the PHR, a significant decrease in the area of the middle rim, and a notable decrease in the area of the SHR. The loading of HC increased the area of the PHR in most derivatives, with the most pronounced increase observed in 2,6-D-MeβCD and 6-MeβCD. The analysis of interaction energies and binding free energies demonstrated that the binding of HC to methylated CD derivatives is thermodynamically more favorable than to βCD, with the strongest association observed for 6-MeβCD, 2-MeβCD, and 2,3-D-MeβCD.

Cyclodextrins (CDs) can enhance the stability and bioavailability of pharmaceutical compounds by encapsulating them within their cavities. This study utilized molecular dynamics simulations to investigate the interaction mechanisms between hydrocortisone (HC) and various methylated CD derivatives. The results reveal that the loading of HC into CD cavities follows different mechanisms depending on the degree and position of methylation. Loading into βCD and 6-MeβCD was more complete, with the hydroxyl groups of HC facing the primary hydroxyl rim (PHR) and the ketone side facing the secondary hydroxyl rim (SHR). In contrast, 2,3-D-MeβCD and 2,6-D-MeβCD showed a different loading mechanism, with the ketone side facing the PHR and the hydroxyl groups facing the SHR. The root mean square fluctuation (RMSF) analysis demonstrated that methylation increases the flexibility of CD heavy atoms, with 3-MeβCD and 2,3-D-MeβCD exhibiting the highest flexibility. However, upon inclusion of HC, 3-MeβCD, 2,3-D-MeβCD, 2-MeβCD, and 6-MeβCD showed a significant reduction in flexibility, suggesting a more rigid structure that effectively retains HC within their cavities. The radial distribution function revealed a significant reduction in the number of water molecules within the innermost layer of the methylated CD cavities, particularly in TMeβCD, indicating a decrease in polarity. The presence of HC led to the release of high-energy water molecules, creating more favorable conditions for HC loading. Conformational analysis showed that methylation caused a partial decrease in the area of the PHR, a significant decrease in the area of the middle rim, and a notable decrease in the area of the SHR. The loading of HC increased the area of the PHR in most derivatives, with the most pronounced increase observed in 2,6-D-MeβCD and 6-MeβCD. The analysis of interaction energies and binding free energies demonstrated that the binding of HC to methylated CD derivatives is thermodynamically more favorable than to βCD, with the strongest association observed for 6-MeβCD, 2-MeβCD, and 2,3-D-MeβCD. [ABSTRACT FROM AUTHOR]

As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5–10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-β-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent. [ABSTRACT FROM AUTHOR]

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG—thermogravimetry; DTG—derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host–guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability. [ABSTRACT FROM AUTHOR]

Self-assembled peptide hydrogels possess remarkable biological activity and biocompatibility. When utilized for local drug delivery, they require enhanced mechanical properties and the ability to facilitate controlled release of drugs. Herein, we present the design and synthesis of a supramolecular hydrogel (Fmoc-GFFG/SBE-β-CD). The hydrogel incorporates host–guest interactions between a self-assembling peptide (Fmoc-GFFG) and cyclodextrin molecules (SBE-β-CD) to improve the viscoelastic strength of the hydrogel while maintaining biocompatibility. With remarkable shear-thinning properties, the Fmoc-GFFG/SBE-β-CD hydrogel exhibits enhanced in vivo retention time, thereby facilitating the development of an injectable drug delivery system. Using 10-hydroxycamptothecin (HCPT) as a model drug, we develop a hydrogel system (Fmoc-GFFG/SBE-β-CD@HCPT) that capitalizes on the inclusion complex formation between SBE-β-CD and HCPT. The resulting composite hydrogels effectively prevent the agglomeration of drug molecules, ensuring the sustained release of HCPT while preserving its anticancer efficacy. The findings presented in this work establish a foundation for the broadening of peptide-based biomaterials and offer a promising avenue for the development of sophisticated drug delivery systems. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are durable synthetic pollutants that persist in the environment and resist biodegradation. Ion-transfer electrochemistry at aqueous–organic interfaces is a simple strategy for the detection of ionised PFAS. Herein, we investigate the modulation of the ion transfer voltammetry of perfluorooctanoate (PFOA) at liquid–liquid micro-interface arrays by aqueous phase bovine serum albumin (BSA) or β-cyclodextrin (β-CD) and examine the determination of association constants for these binding interactions. By tracking the ion transfer current due to ionised, uncomplexed PFOA as a function of BSA or β-CD concentration, titration curves are produced. Fitting of a binding isotherm to these data provides the association constants. The association constant of PFOA with the BSA determined in this way was ca. 105 M−1 assuming a 1 : 1 binding. Likewise, the association constant for PFOA with β-CD was ca. 104 M−1 for a 1 : 1 β-CD-PFOA complex. Finally, the simultaneous effect of both BSA and β-CD on the ion transfer voltammetry of PFOA was studied, showing clearly that PFOA bound to BSA is released (de-complexed) upon addition of β-CD. The results presented here show ion transfer voltammetry as a simple strategy for the study of molecular and biomolecular binding of ionised PFAS and is potentially useful in understanding the affinity of different PFAS with aqueous phase binding agents such as proteins and carbohydrates. [ABSTRACT FROM AUTHOR]

The cyclic oligosaccharide β‐cyclodextrin (β‐CDx) is investigated regarding its ability on principle to reduce the debranching activity of pullulanase (PUL) or even terminate the enzymatic hydrolysis process of starch polymers completely. For this purpose, dissolved β‐CDx (aqueous solution) is mixed with the diluted PUL compound (solution) and conditioned (stirred at 40 °C for various durations [0, 20, 40, and 60 min; at 26.75 nmol β‐CDx U−1] and at various β‐CDx dosages [5.35, 13.375, 26.75, and 53.5 nmol β‐CDx U−1; reaction time 60 min]). The PUL‐CDx‐mixtures are subsequently added to a 2.5% w/w starch solution (related to the initial specific debranching activity; 1593.6 NPUN g−1/557.8 U g−1) and gently stirred for 20 min at 40 °C before final thermal inactivation. The obtained samples are diluted and characterized molecularly, i.e., by means of size exclusion chromatography (SEC). An increasing β‐CDx dosage reduces the degree of molecular degradation systematically reflecting a successively reduced enzyme activity. However, the reaction time (PUL‐CDx‐mixture) has no impact on the enzyme's activity since the starch degradation is marginally and the SEC‐chromatograms similar to the one of the initial starch. Restrictions of the enzyme inhibiting effect of β‐CDx are found terminating the hydrolysis process in a starch suspension. [ABSTRACT FROM AUTHOR]

Adenosine, as a water-soluble active substance, has various pharmacological effects. This study proposes a layer-by-layer assembly method of composite wall materials, using hydroxypropyl- β -cyclodextrin as the inner wall and whey protein isolate as the outer wall, to encapsulate adenosine within the core material, aiming to enhance adenosine microcapsules' stability through intermolecular interactions. By combining isothermal titration calorimetry with molecular modeling analysis, it was determined that the core material and the inner wall and the inner wall and the outer wall interact through intermolecular forces. Adenosine and hydroxypropyl- β -cyclodextrin form an optimal 1:1 complex through hydrophobic interactions, while hydroxypropyl- β -cyclodextrin and whey protein isolate interact through hydrogen bonds. The embedding rate of AD/Hp- β -CD/WPI microcapsules was 36.80%, and the 24 h retention rate under the release behavior test was 76.09%. The method of preparing adenosine microcapsules using composite wall materials is environmentally friendly and shows broad application prospects in storage and delivery systems with sustained release properties. [ABSTRACT FROM AUTHOR]

The present work focuses on the inclusion complexations (ICs) of rosuvastatin calcium (RSV) with beta (b) ve gama (g) derivatives of native cyclodextrins (CDs) and investigate effects on improved solubility and dissolution rate. The phase solubility studies illustrated that RSV solubility increased in the presence of γCD with a negative deviation that indicates AN type diagrams, while βCD showed Bs type, upon addition of βCD, an increase in the solubility of the drug was observed up to a particular point. ICs of RSV were prepared with β and γCD by at 1:1, 1:2 and 1:4 different molar ratios by freeze drying method. FT-IR and DSC results revealed formation of ICs between RSV and CD. High drug loading efficiency was obtained for all ICs in the range of 99.41-101.84%. Water solubility studies showed that βCD ICs have increased solubility of RSV about 1.3 times regardless of CD ratios(p>0.05). As compared to βCD ICs, RSV solubility was significantly greater in γCD ICs and increased up to 1.45, 1.72 and 2.00 fold at 1:1, 1:2 and 1:4 ratio, respectively. Conspicuously, RSV solubility increased with increasing ratio of γCD(p<0.05). Compared dissolution profiles with pure RSV, all ICs showed improved dissolution rates and immediate release profiles. However multiple point comparison of dissolution profiles indicated that γCD ICs have higher drug release. Particularly γCD ICs at 1:4 ratio released the highest RSV with 95.12% at 3 min and 100% completion in 15 min. It is concluded that γCD provided a better improvement on RSV solubility and dissolution rate than βCD. [ABSTRACT FROM AUTHOR]

A key goal in current research on industrial curdlan production is the expansion of carbon sources for fermentation. In this study, a recombinant bacterial strain, sp-AmyAXCC, capable of fermenting and synthesizing curdlan using dextrin as a carbon source, was produced via heterologous expression of IPTG-inducible α-amylase from Xanthomonas campestris NRRL B-1459 in Agrobacterium tumefaciens ATCC31749. External expression of the enzyme was confirmed by western blotting, and the expression levels of exogenous proteins during the fermentation process were monitored. Additionally, the properties of the curdlan product were characterized using attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray diffraction. The recombinant strain produced curdlan at a titer of 30.40 ± 0.14 g/L, gel strength of 703.5 ± 34.2 g/cm2, and a molecular weight of 3.58 × 106 Da, which is 33% greater than the molecular weight of native curdlan (2.69 × 106 Da). In the batch fermentation of sp-AmyAXCC with 12% dextrin as a carbon source, the titer of curdlan was 66.7 g/L with a yield of 0.56 g/g, and a productivity rate of 0.62 g/L/h at 108 h. The results of this study expand the substrate spectrum for Agrobacterium fermentation in curdlan production and provides guidance for further industrialization of curdlan production. [ABSTRACT FROM AUTHOR]

Natural vitamin E was extracted from crude palm oil and palm fatty acid distillate, both of which were converted into biodiesel before the extraction process. To enhance the stability of vitamin E, the study investigated the formation of inclusion complexes between vitamin E and β-cyclodextrin and hydroxypropyl-β-cyclodextrin. The results demonstrated improved thermal and light stabilities, prolonging the shelf life at room temperature while maintaining the antioxidant activity of vitamin E. Furthermore, the study successfully applied these complexes to poly(lactic acid) (PLA) fabrics, a biodegradable natural polymer, without altering their appearance. These findings underscore the potential of utilizing natural vitamin E from CPO and PFAD sources in the form of inclusion complexes for textile applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Triblock copolymers of poly(ethylene oxide) and poly(propylene oxide)-based matrices, such as Poloxamer 407 (P407) or Pluronic® F127, are extensively utilized in drug delivery and permeation systems due to their FDA approval and listing in the US and European Pharmacopoeias. The study hypothesizes that incorporating 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and the celecoxib-HP-β-CD inclusion complex into a 16 wt% P407 and chitosan blend in an aqueous acetic acid solution will affect the system's rheological and structural properties. Rheological, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) experiments were conducted to assess the impact of acetic acid and chitosan on the 16 wt% P407 and chitosan blend. Additionally, in vitro drug release studies were performed to monitor the drug release profile over time. The addition of HP-β-CD was found to inhibit gel formation in the 16 wt% P407 and chitosan blend. However, the presence of the celecoxib-HP-β-CD inclusion complex showed no significant structural effects compared to P407 blended with chitosan alone. Rheological and SAXS analyses demonstrated that acetic acid led to the formation of a lamellar phase due to the lower pH, facilitating injectability. The presence of chitosan in acetic acid resulted in the detection of a hexagonal phase, affecting the release of celecoxib. [ABSTRACT FROM AUTHOR]

A novel zero-valent iron nanoparticles impregnated cross-linked chitosan grafted β-cyclodextrin (Fe-CCS-g-β-CD) adsorbent was fabricated to eliminate cloxacillin from water. The characterization of Fe-CCS-g-β-CD was done using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with energy dispersive X-ray (EDX) spectroscopy and thermogravimetry–differential thermal analysis (TGA-DTA) techniques. Response surface methodology (RSM) using Box-Behnken design (BBD) was utilized to optimize the independent variables (contact time, pH, adsorbent dose and initial cloxacillin concentration) for the adsorption of cloxacillin onto Fe-CCS-g-β-CD. The maximum removal of cloxacillin (99.93%) was achieved when the contact time, pH, adsorbent dose and initial cloxacillin concentration were 40 min., 6.5, 20 mg and 50 mg/L, respectively. The adsorption data were probed by Langmuir, Freundlich, Temkin, Dubinin-Radushkevich and Flory–Huggins isotherm models. Freundlich isotherm model described well the adsorption process. The kinetic data were examined by surface based (pseudo-first order, pseudo-second order and Elovich models) and diffusion based (Furusawa-Smith external model, Urano-Tachikawa intra-particle and Bangham's pore diffusion models) kinetic models. Pseudo-second order kinetic model fitted more accurately to the kinetic data. Diffusion based kinetic models suggested that various adsorption stages were occurred to control the adsorption process. The adsorption and pH studies indicated that C-π cation interaction was developed between the delocalized electron of zero-valent iron with aromatic ring of β-cyclodextrin and π-π interaction were also possible between phenolic ring of cloxacillin and glucose monomer of chitosan which enhance the removal efficiency of cloxacillin. The adsorption–desorption studies were carried out upto 10 cycles and suggested that the adsorbent can be effectively used for the removal of cloxacillin from aqueous environment. [ABSTRACT FROM AUTHOR]

In the present study, flat cellulose acetate ultrafiltration membranes were prepared first by nonsolvent induced phase separation method. Then chiral membranes for separating the enantiomers were prepared by grafting the ultrafiltration membranes using ethylenediamine‐β‐cyclodextrin as the chiral selector and epichlorohydrin as the spacer arm. The pure water permeability of the ultrafiltration membrane was around 115 L·m−2·h−1·bar−1. The properties of the chiral membranes were characterized using infrared spectroscopy (ATR‐FTIR), X‐ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The chiral membrane performance in enantiomer separation was evaluated with racemates, such as mandelic acid (MA), 2‐chloromandelic acid (2‐ClMA), 4‐chloromandelic acid (4‐ClMA), and methyl mandelate (MM). The influence of feed concentration on the separation efficiency was also investigated. The results indicated that the enantiomeric excess percentages (e.e%) of the racemic mixtures for these four chiral compounds were up to 31.8%, 25.4%, 17.8%, and 32.6%, respectively. The binding free energy of the chiral selector with the (S)‐enantiomer calculated by molecular dynamics simulations was stronger than that with the (R)‐enantiomer, which was consistent with the experimental results (higher concentration of (R)‐enantiomer in the permeate). This supports the affinity absorption‐separation mechanism. [ABSTRACT FROM AUTHOR]

An aqueous solution of chlorinated polyethylene glycol (Cl-PEG-Cl) and α-cyclodextrin (α-CD) was used to form inclusion complexes, which several α-CDs are threaded into the linear PEG chain and produced a so-called polypseudorotaxane (PPRx). By attaching 4-ethylaniline as the blocking agent to the chlorinated PEG chain ends, the complex will be stabilized, resulting in the formation of so-called polyrotaxane (PRx) (also known as molecular necklace). Finally, crosslinked αCD-based PRx with a tubular structure was formed via the condensation reactions between α-cyclodextrins and epichlorohydrin. Using concentrated NaOH solution, polymer chains were then removed from complexes, resulting in the so-called molecular tube (MT). This novel method led to the improvement in polyrotaxane conversion with less production steps and reduced materials overall costs. Resulting products in each section were characterized by 1H and 13C nuclear magnetic resonance spectroscopies (1H-NMR and 13C-NMR), from which complex inclusion ratio and length of the nanotubes were estimated. XRD was also used to confirm tubular structure of the inclusion complexes. [ABSTRACT FROM AUTHOR]

Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette's syndrome. Despite its therapeutic benefits, ARZ is characterized by a poor water solubility which provoked the development of various delivery systems in order to enhance its solubility. In the present work, a nanoscale drug delivery system based on N,N-dimethylacrylamide (DMAA) and β-cyclodextrin triacrylate (β-CD-Ac3) as potential aripiprazole delivery vehicles was developed. The nanogels were synthesized by free radical polymerization of DMAA in the presence of β-CD-Ac3 as a crosslinking agent and then loaded with ARZ via host-guest inclusion complexation. The blank- and drug-loaded nanogels were evaluated using different methods. Fourier transform infrared (FTIR) spectroscopy was employed to confirm the incorporation of β-CD moieties into the polymer network. Dynamic light scattering (DLS) was used to study the size of the developed systems. The samples exhibited a monomodal particle size distribution and a relatively narrow dispersity index. The hydrodynamic diameter (Dh) of the gels varied between 107 and 129 nm, with a tendency for slightly larger particles as the β-CD-Ac3 fraction increased. Loading the drug into the nanocarrier resulted in slightly larger particles than the blank gels, but their size was still in the nanoscopic range (166 to 169 nm). The release profiles in PBS were studied and a sustained release pattern with no significant burst effect was observed. A cytotoxicity assessment was also conducted to demonstrate the non-toxicity and biocompatibility of the studied polymers. [ABSTRACT FROM AUTHOR]

The extensive use of per- and polyfluoroalkyl substances (PFASs) in industrial consumer products has led to groundwater contamination, raising concerns for human health and the environment. These persistent chemicals exist in different forms with varying properties, which makes their removal challenging. In this study, we assessed the effectiveness of three different β-cyclodextrin (β-CD) adsorbents at removing a mixture of PFASs, including anionic, neutral, and zwitterionic compounds, at neutral pH. We calculated linear partition coefficient (Kd) values to quantify the adsorption affinity of each PFAS. β-CD polymers crosslinked with hexamethylene diisocyanate (β-CD-HDI) and epichlorohydrin (β-CD-EPI) displayed some adsorption of PFASs. Benzyl chloride β-CD (β-CD-Cl), an adsorbent that had not been previously reported, was also synthesized and tested for PFAS adsorption. β-CD-Cl exhibited higher PFAS adsorption than β-CD-HDI and β-CD-EPI, with log Kd values ranging from 1.9 L·g−1 to 3.3 L·g−1. β-CD-Cl displayed no affinity for zwitterionic compounds, as opposed to β-CD-HDI and β-CD-EPI, which removed N-dimethyl ammonio propyl perfluorohexane sulfonamide (AmPr-FHxSA). A comparison between Kd values and the log Kow of PFAS confirmed the significant role of hydrophobic interactions in thee adsorption mechanism. This effect was stronger in β-CD-Cl, compared to β-CD-HDI and β-CD-EPI. While no effect of PFAS charge was observed in β-CD-Cl, some influence of charge was observed in β-CD-HDI and β-CD-EPI, with less negative compounds being more adsorbed. The adsorption of PFASs by β-CD-Cl was similar in magnitude to that of other adsorbents proposed in literature. However, it offers the advantage of not containing fluorine, unlike many commonly proposed adsorbents. [ABSTRACT FROM AUTHOR]

Introduction. The Tay-Sachs disease is a progressive neurodegenerative disorder that is caused by a genetic mutation in the HEXA gene coding the lysosomal α-subunit of β-hexosaminidase A. Currently, there is no effective treatment for Tay-Sachs. Induction of exocytosis as a potential treatment approach is suggested to restore lysosomal enlargement in several lysosomal storage diseases. Here, we aimed to test the therapeutic potential of two small molecules, δ-tocopherol and hydroxypropyl-β-cyclodextrin, in fibroblast and neuroglia cells derived from Hexa-/-Neu3-/- mice and Tay-Sachs patients. Method. The effect of two small molecules on lysosomal enlargement and GM2 accumulation in lysosomes was examined by LysoTracker staining and immunocytochemical colocalization analysis for GM2 and LAMP1. qRT-PCR and fluorometric enzyme assay were also used to investigate the effect of combined treatment on the level of neuraminidase 1, a negative regulator of exocytosis. Results. Single treatment with δ-tocopherol (5-40 μM) and hydroxypropyl-β-cyclodextrin (10-50 μM) for 48 hours led to significant induction of lysosomal exocytosis. We demonstrated that the combined treatment with δ-tocopherol (10 μM) and hydroxypropyl-β-cyclodextrin (25 μM) resulted in a significant reduction of lysosomal GM2 and downregulation of lysosomal Neu1 expression. Conclusion. In this study, we demonstrated that inducing exocytosis by δ-tocopherol and hydroxypropyl-β-cyclodextrin might have therapeutic potential to reduce GM2 storage and pathology in Tay-Sachs cells. [ABSTRACT FROM AUTHOR]

This document is a list of references for a research article on the role of cyclodextrins in various biological processes. The references include studies on the solubilizing power of methyl-betacyclodextrins, the entry of fluorescently labeled methyl-beta-cyclodextrin into intestinal cells, the depletion of gangliosides and cholesterol by cyclodextrin derivatives, the effects of cyclodextrin-membrane interaction on drug delivery and membrane structure, the inhibitory effect of anandamide on sensory neuropeptide release, the antinociceptive effects of lipid raft disruptors, the effects of lipid raft disruptors on cell membrane fluidity, the analgesic effects of lipid raft disruption, the effect of cyclodextrin and membrane lipid structure on cyclodextrin-lipid interaction, the activation of capsaicin receptors by lipoxygenase products, the development of TRPV1-targeted drugs for pain conditions, the clearance of aggregated α-synuclein by TFEB activation, the cytotoxicity of beta-cyclodextrin derivatives, the regulation of membrane protein structure and function by lipid nano-environment, the depletion of cholesterol in model lipid membranes by cyclodextrin, the requirement of cholesterol for TRPV1 function and membrane expression, the effects of cyclodextrins on drug permeation through biological membranes, the molecular mechanism of cyclodextrin-mediated cholesterol extraction, the heterogeneity of lipid rafts, and [Extracted from the article]

Most antiviral and anticancer nucleosides are prodrugs that require stepwise phosphorylation to their triphosphate nucleotide form for biological activity. Monophosphorylation may be rate-limiting, and the nucleotides may be unstable and poorly internalized by target cells. Effective targeting and delivery systems for nucleoside drugs, including oligonucleotides used in molecular therapeutics, could augment their efficacy. The development of a carrier designed to effect selective transmembrane internalization of nucleotides via the asialoglycoprotein receptor (ASGPr) is now reported. In this work, the polycationic, polygalactosyl drug delivery carrier heptakis[6-amino-6-deoxy-2-O-(3-(1-thio-β-D-galactopyranosyl)-propyl)]-β-cyclodextrin hepta-acetate salt (GCyDAc), potentially a bifunctional carrier of (poly)nucleotides, was modeled by molecular docking in silico as an ASGPr-ligand, then synthesized for testing. The antivirals arabinosyl adenine (araA, vidarabine, an early generation antiviral nucleoside), arabinosyl adenine 5′-monophosphate (araAMP), and 12-mer-araAMP (p-araAMP) were selected for individual formulation with GCyDAc to develop this concept. Experimentally, beta cyclodextrin was decorated with seven protonated amino substituents on the primary face, and seven thiogalactose residues on its secondary face. AraA, araAMP, and p-araAMP were individually complexed with GCyDAc and complex formation for each drug was confirmed by differential scanning calorimetry (DSC). Finally, the free drugs and their GCyDAc complexes were evaluated for antiviral activity using ASGPr-expressing HepAD38 cells in cell culture. In this model, araA, araAMP, and p-araAMP showed relative antiviral potencies of 1.0, 1.1, and 1.2, respectively. In comparison, GCyDAc-complexes of araA, araAMP, and p-araAMP were 2.5, 1.3, and 1.2 times more effective than non-complexed araA in suppressing viral DNA production. The antiviral potencies of these complexes were minimally supportive of the hypothesis that ASGPr-targeted, CyD-based charge-association complexation of nucleosides and nucleotides could effectively enhance antiviral efficacy. GCyDAc was non-toxic to mammalian cells in cell culture, as determined using the MTS proliferation assay. [ABSTRACT FROM AUTHOR]

The main objective of this study was to investigate the influence of carbohydrate intake (cyclodextrin) on performance during the performance of two consecutive workouts of the day (WODs) lasting 20 min each. Twenty-one male CrossFit (CF) athletes (29.5 ± 4.3 years; 72.81 ± 12.85 kg; 1.74 ± 0.06 m; 3.41 ± 1.21 years of experiences) participated in a crossover, randomized, and double-blind study. The effect of supplementation with 30 g of cyclodextrin (SG) (Cluster Dextrin®) or placebo (PG) (Bolero Advanced Hydration®) was evaluated on the performance of two specific WOD. Additionally, the effect on handgrip maximum strength, countermovement jump (CMJ), Wingate test, and 1 RM bench press test was evaluated. The effect on blood glucose and lactate was also evaluated. No differences were found in time, height, and power (W/Kg) in CMJ. However, there was a percentage improvement in CMJ jump power (W) (p < 0.05) between the groups, assuming an improvement in performance due to the intervention. Moreover, both conditions experimented differences in execution speed between sets (p < 0.05) in pre-WOD, and differences in post-WOD only in the placebo group, as well as decreases in this variable per repetition across the set (p < 0.01) in both conditions. However, no differences were found in the rest of the variables. Supplementation with 30 g of cyclodextrin did not have any metabolic or performance effects in CF tests. Although some differences between groups were observed in CMJ and power tests for bench press, the data are not conclusive and further research is needed in this regard. [ABSTRACT FROM AUTHOR]

Cyclodextrins (CDs) are truncated cone‐like structures that are natural cyclic oligosaccharides. Here, a simple preparation method for super porous poly(α‐CD), poly(β‐CD), and poly(γ‐CD) cryogels crosslinking with divinyl sulfone at 150%, 100% and 125% mole ratios with respect to the α‐CD, β‐CD, and γ‐CD molecules, respectively, under cryogenic conditions, is reported. The interconnected homogeneous pore distribution of CD‐based cryogels with pore sizes in the range of 5–100 μm is confirmed by SEM analysis. The CD‐based cryogels weighing 10 mg are determined as hemocompatible with <1% hemolysis ratios and >79% blood clotting indexes; whereas the same materials weighing 1 mg are biocompatible with >75% cell viability on L929 fibroblasts. Additionally, active agent adsorption/delivery efficiencies of CD‐based cryogels utilizing two active agents, Bisphenol A (BPA, a carcinogenic compound) and Curcumin (CUR, a polyphenolic compound), are individually evaluated. It was revealed that p(γ‐CD) cryogels exhibited the highest active agent loading capacity for BPA, 87 ± 13 mg/g, whereas p(α‐CD) cryogels showed the highest loading capacity for CUR, 136 ± 4 mg/g. Moreover, the active agent release from p(α‐CD), p(β‐CD), and p(γ‐CD) cryogel networks at pH 7.4 and 37°C were determined as 40.6 ± 2, 35.3 ± 2, and 34 ± 1 mg/g for BPA, and 1.07 ± 0.2, 1.27 ± 0.1, and 1.37 ± 0.1 mg/g for CUR, respectively, within 96 h. [ABSTRACT FROM AUTHOR]

Designing suitable adsorbents is a key challenge in the recovery of Au(I) from thiosulfate gold‐leaching solutions as the ideal adsorbent not only possesses abundant active sites with high affinities and selectivities toward Au(I), but also demonstrates fast recovery of Au(I) at high purity and large capacity. Herein, guided by theoretical calculations, a water‐insoluble inclusion complex is synthesized using β‐cyclodextrin (β‐CD) and diphenylphosphine (DPP) as host and guest molecules, respectively, by a steric hindrance strategy for highly efficient and selective Au(I) recovery. The prepared β‐CD@DPP exhibits outstanding Au(I) adsorption performance, with a saturated loading capacity of 146.28 mg g−1. The excellent adsorption performance of β‐CD@DPP for Au(I) is mainly attributed to the full exposure of the adsorption site and the weakly alkaline adsorption environment. Furthermore, β‐CD@DPP demonstrates outstanding selectivity for Au(I) in a Cu─NH3─thiosulfate gold‐leaching solution, and the Au(I) recovery rate is higher than 99%. Synthesis of β‐CD@DPP primarily depends on the weak interactions between DPP and β‐CD. Mechanism of adsorption of Au(I) on β‐CD@DPP involves ligand exchange between PPh2− and [Au(S2O3)2]3−. This study provides a new idea and material preparation method for highly efficient, selective, and large‐capacity recovery of Au(I) from thiosulfate leaching solution. [ABSTRACT FROM AUTHOR]