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Neurodegenerative diseases such as Alzheimer's are very common today. Idebenone (IDE) is a potent antioxidant with good potential for restoring cerebral efficiency in cases of these and other medical conditions, but a serious drawback for the clinical use of IDE in neurological disorders lies in its scarce water solubility, which greatly inhibits its bioavailability. In this work, we prepared the inclusion complex of IDE with randomly methylated β-cyclodextrin (RAMEB), resulting in improved water solubility of the included drug; then its in vitro biological activity and ex vivo permeability was evalutated. The solid complex was characterized through FT-IR spectroscopy, Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC). A 78-fold improvement of the solubility of IDE in water resulted, together with a strong 1:1 host-guest interaction (association constant of 12630 M -1 ), and dissolution of the complex within 15 min, all evidenced during the in-solution studies. Biological in vitro studies were then performed on differentiated human neuroblastoma cells (SH-SY5Y) subjected to oxidative stress. Pretreatment with IDE/RAMEB positively affected cell viability, promoted the nuclear translocation of Nrf2, and increased the levels of GSH as well as those of the endogenous antioxidant enzymes Mn-SOD and HO-1. Lastly, the complexation significantly improved the permeation of IDE through isolated rat nasal mucosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To enhance curcumin's application in photodynamic inactivation (PDI) of liquid foods, a supramolecular complex of biotin-modified β-cyclodextrin and curcumin (Biotin-CD@Cur) was synthesized. This complex significantly improves curcumin's solubility, stability, and PDI efficiency. Following PDI, Biotin-CD@Cur can be magnetically separated from the liquid matrix using streptavidin-coated magnetic beads (SA-MBs). Leveraging the reversible binding between streptavidin and biotin, Biotin-CD@Cur and SA-MBs fully dissociate in ultrapure water at 70 °C, enabling reuse. Antibacterial tests in freshly squeezed orange juice demonstrated that a low dose of 1.5 J/cm 2 from a 420 nm LED array and 10 μg/mL of Biotin-CD@Cur achieved log reductions of 3.287 ± 0.015 for Staphylococcus aureus and 2.961 ± 0.011 for Listeria monocytogenes, while preserving the juice's flavor and nutritional contents. The PDI system remained effective for at least four cycles. Ultra-performance liquid chromatography and atomic absorption spectroscopy confirmed no residues of system components in the juice after magnetic separation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aspergillus flavipes L-methionine γ-lyase (MGL) has been authenticated as a powerful anticancer agent towards various solid tumors, however, the catalytic efficiency and stability of this enzyme remains the main challenge for its further in vivo applications. Thus, the objective of this study was to enhance the catalytic efficiency, structural stability of A. flavipes MGL, in addition to boost their anticancer activity, via conjugation with β-cyclodextrin. The purified A. flavipes MGL was (38.1 μmol/mg/min) was conjugated with β-cyclodextrin, with immobilization yield 80%. The conjugation process of MGL with β-cyclodextrin was verified from the FTIR analysis, molecular docking analysis, ensuring the covalent conjugation process via the hydrogen, and hydrophobic interactions with the cyclodextrin hydroxyl groups and MGL surface amino acids residues. The free and CD-MGL have the same optimum reaction temperature 37 °C, reaction pH 7.5 and pH stability pH 6.5-8.0. The CD-MGL conjugates had a significant stability to proteinase K and trypsin digestion. The affinity of CD-MGL was increased by ~ 2 folds to L-methionine (K M 3.1 mM), compared to the free one (K M 7.2 mM), as well as the catalytic efficiency of MGL was increased by 1.8 folds upon cyclodextrin conjugation. The higher affinity of CD-MGL for L-methionine might be due to re-orientation of the MGL to bind with the substrate by multiple interactions hydrogen, hydrophobic and covalent bonds compared to the free one. The thermal stability of MGL was increased by ~ 2 folds for the tested treatments, upon cyclodextrin conjugation. The in vitro anticancer activity of CD-MGL was enhanced by 2 folds against the HCT-116 (IC 50 value 13.9 μmol/mg/min) and MCF7 (IC 50 value 9.6 μmol/mg/min), compared to the free MGL (~ 21.4 μmol/mg/min). The enzymes displayed a significant activity against the proliferation of Ehrlich ascites carcinoma in vivo, with an obvious improvement on the liver tissues, as revealed from the histopathological sections., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval and consent to participate The animal experiments were conducted according to the guidelines of the Institutional Animal Care and Use Committee (IACUC) at the Faculty of Medicine, Zagazig University, and confirmed to follow NIH guidelines under protocol 15–08-263. All the animal experiments were conducted according to the ARRIVE guidelines. All the experimental protocols were approved by the ethics committee/Institutional Review Board of the Faculty of Medicine, Zagazig University, Egypt. Consent for publication Not applicable., (© 2024. The Author(s).)

Chronic diabetic wounds suffer from severe complications caused by long-term high levels of oxidative stress and bacterial infection. Quercetin (Que) has excellent anti-inflammatory, antioxidant, and antibacterial activity, making it a promising drug to address the above issues. To exploit the benefits of Que in a more effective and sustained way to treat diabetic wounds, carboxymethyl β-cyclodextrin (CMCD) was synthesized and conjugated to keratin, then complexed with Que to form Que@Ker-CMCD inclusion, followed by electrospinning with polyurethane (PU) to afford Que@Ker-CMCD/PU mats. The approach significantly enhanced water solubility, bioavailability, and sustained release of Que. Crucially, these mats exhibited robust antioxidant and antibacterial activities. Moreover, the mats fostered an environment conducive to cell proliferation, migration, angiogenesis, and re-epithelialization, pivotal processes in wound healing and remodeling. Consequently, a marked acceleration in remodeling chronic diabetic wounds was observed. In conclusion, this study introduces a novel therapeutic strategy that not only harnesses the multifaceted benefits of Que but also enhances its delivery and performance, offering a promising avenue for the effective treatment of chronic diabetic wounds.

Background: Cancer ranks as the second most common cause of mortality as depicted by the World Health Organization, with one in six deaths being cancer-related mortality. Taking the lead in females, breast cancer is the most common neoplasm. Raloxifene, a selective estrogen receptor modulator, has been utilized as a chemotherapeutic agent for the treatment of breast cancer in postmenopausal women. However, its poor aqueous solubility hinders its clinical applications. Beta-cyclodextrin-based framework is a novel class of nano-vectors that used to potentiate the solubility and dissolution rate of poorly soluble drugs., Aim: The present study investigates the solubility and dissolution rate enhancement as well as the potential cytotoxic activity of raloxifene-loaded nanosponges formulation., Methods: The fabrication and optimization of cyclodextrin nanosponges crosslinked with diphenyl carbonate was portrayed through stoichiometric selection of cyclodextrin-to-crosslinker ratio. The complexation phenomenon and nanosponges formation were validated using FTIR, PXRD, TEM, and SEM examination., Results: Raloxifene-loaded nanosponges exhibited a 440±8.5 nm particle size, a negative zeta potential of 25.18±2.3 mV and a partial drug incorporation. Moreover, the drug loaded nanosponges demonstrated an in-vitro significantly enhanced dissolution behavior. Furthermore, the in-vitro cytotoxicity of the raloxifene-loaded nanosponges on MCF-7 breast cancer cell lines was statistically significant compared to the complex-free raloxifene., Conclusion: The cytotoxic behavior provided evidence that the incorporation of raloxifene within the nanosponges structure enhanced its anticancer activity and represents a potential nanocarrier for anticancer agent delivery., Competing Interests: No conflicts of interest are disclosed by the authors of this work., (© 2024 Alwattar and Mehanna.)

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-β-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Daniel W. Armstrong has a potential research conflict of interest due to a financial interest with the company AZYP, LLC. A management plan has been created to preserve objectively in research in accordance with UTA policy, (Copyright © 2024. Published by Elsevier B.V.)

The mammalian plasma membrane is known to contain domains with varying lipid composition and biophysical properties. However, studying these membrane lipid domains presents challenges due to their predicted morphological similarity to the bulk membrane and their scale being below the classical resolution limit of optical microscopy. To address this, we combine the solvatochromic probe di-4-ANEPPDHQ, which reports on its biophysical environment through changes in its fluorescence emission, with spectrally resolved single-molecule localisation microscopy. The resulting data comprises nanometre-precision localisation coordinates and a generalised polarisation value related to the probe's environment - a marked point pattern. We introduce quantification algorithms based on topological data analysis (PLASMA) to detect and map nano-domains in this marked data, demonstrating their effectiveness in both artificial membranes and live cells. By leveraging environmentally sensitive fluorophores, multi-modal single molecule localisation microscopy, and advanced analysis methods, we achieve nanometre scale mapping of membrane properties and assess changes in response to external perturbation with methyl-β-cyclodextrin. This integrated methodology represents an integrated toolset for investigating marked point pattern data at nanometre spatial scales., (© 2024. The Author(s).)

The chiral recognition and separation of enantiomers are of great importance for biological research and the pharmaceutical industry. Preparing homochiral materials with adjustable size and chiral binding sites is beneficial for achieving an efficient chiral recognition performance. Here, a homochiral covalent organic framework membrane modified with β-cyclodextrin (CD-COF) was constructed, which was subsequently utilized as an electrochemical sensor for the enantioselective sensing of tryptophan (Trp) molecules. The preferential adsorption of l-Trp over d-Trp at the β-CD sites can enhance the surface charge density and hydrophilicity of the CD-COF membrane, resulting in an increased transmembrane ionic current. Trp enantiomers with concentrations down to 0.28 nM can be effectively discriminated. The l-/d-Trp recognition selectivity increases with the Trp concentration and reaches a value of 19.2 at 1 mM. The selective adsorption of l-Trp to the CD-COF membrane will also hinder its transport, resulting in a l-/d-Trp permeation selectivity of 15.3. This study offers a new strategy to construct homochiral porous membranes and achieve efficient chiral sensing and separation.

Thiophenol (PhSH) is an important industrial intermediate but displays significant toxicity towards environmental and biological systems. Here, we introduce a supramolecular system based on β-cyclodextrin (β-CD) and boron dipyrromethene (BODIPY) as a ratiometric fluorescence probe to discriminate PhSH in environmental water samples, cells, and in vivo. In aqueous solutions, BODIPY shows extremely weak fluorescence intensity due to its aggregation into nanometer-sized clusters, which prevents its interaction with thiols. However, within a β-CD environment, it can selectively and sensitively detect PhSH. Also, the stability of the probe was significantly improved. The mechanism studies based on stoichiometry, NMR spectroscopy, and theoretical calculation revealed distinct intermolecular interactions between β-CD and BODIPY, including host-guest interactions and hydrogen bonds. Low limit of detection (10.7 nM) and rapid response time (5 min) have been achieved, and the practicality of the supramolecular system (BODIPY@β-CD) has been verified by actual sample analysis. Furthermore, the first hydrogel-based sensing system for portable PhSH detection has been developed, facilitating rapid and on-site colorimetric visualization across both liquid and gas phases. Most importantly, using a low amount of the probe, early stages of low-dose exposure to PhSH can be visualized in living cells and zebrafish. Therefore, BODIPY@β-CD is a robust new monitoring tool for the detection of PhSH in various scenarios, indicating the promising application value of the host-guest supramolecular probe in detecting highly toxic substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled ( 52 Mn) randomly methylated beta-cyclodextrin ([ 52 Mn]Mn-DOTAGA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [ 68 Ga]Ga-DOTA-NAPamide and PGE2 selective [ 68 Ga]Ga-DOTAGA-RAMEB cyclodextrin., Materials and Methods: Post-injection of [ 68 Ga]Ga-DOTA-NAPamide, [ 68 Ga]Ga-DOTAGA-RAMEB, and [ 52 Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter., Results: Although all tracers performed well in tumor identification, the highest standardized uptake values were detected in the [ 68 Ga]Ga-DOTA-NAPamide scans. Corresponding to the ex vivo data, meaningful [ 52 Mn]Mn-DOTAGA-RAMEB accumulation 1 h post-injection confirmed the tumor-targeting potential of the tracer. Temporal changes in PGE2/EP2 expression of the neoplasms may explain the significant differences observed between the tumor uptake of the two cyclodextrin probes and that of the 52 Mn-labelled compound measured 1 h, 4 h, and 3 days post-injection (p≤0.01, p≤0.05)., Conclusion: Although further pharmacokinetical optimization may be required, 52 Mn-labelled cyclodextrin holds potential in melanoma diagnostics and the PET-based longitudinal assessment of tumor-associated PGE2/EP2 expression., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hydrogels have been widely used in biomedical fields including tissue engineering, drug delivery and cell delivery and 3D cell delivery due to abundant water content in their hydrophilic three-dimensional networks and having soft tissue similar to the human body. In recent years, supramolecular hydrogels (SHG) formed by the inclusion complex between polyethylene glycol (PEG) and macrocycles such as cyclodextrin (CD) have attracted much interest due to their excellent biocompatibility and great potential in biomedical. In this research, a carboxymethyl cellulose (CMC)-based graft copolymer was prepared by using acrylic acid (AA) and maleic anhydride functionalized β-CD (β-CD-MA) as comonomers and ammonium persulfate (APS) as initiator. Then, a self-healable supramolecular hydrogel was synthesized by formation of a host-guest inclusion complex between CMC-g-poly (AA-co-β-CD-MA) as host molecule and cytosine- and guanine-modified PEG as guest molecules. The prepared hydrogel was characterized by Scanning Electron Microscope (SEM), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy ( 1 H NMR). The thermal stability of hydrogel was also determined by thermal gravimetric (TGA) and differential scanning calorimetry (DSC) methods. In addition, the loading and release profiles of metformin hydrochloride (MH) drug as a model on hydrogel was investigated. The results indicated that the drug release from the hydrogel peaks around 360 min and aligns with the Ritger-Peppas model. The hydrogel's self-healing property was examined at ambient temperature and 37 °C. It showed 70 % healing in 1.5 h and completed recovery after 9 h., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recently, biopolymers have been used as coagulants/flocculants due to their biodegradability, low cost, and renewability. In this study, an environmentally friendly amine-functionalized starch-based flocculant was successfully prepared. Initially, β-cyclodextrin was grafted onto the starch backbone to increase the number of hydroxyl groups, and this composite was named CD-starch. Subsequently, in order to introduce cationic properties and enhance effective flocculation, CD-starch was modified using amine functional groups. The surface functional groups were engineered by introducing different amine to CD-starch ratios (0.5:1, 1:1, 2:1 w/w), named A-CD-starch 0.5, 1 and 2, respectively. Following the characterization of the synthesized substrate, its performance in the flocculation process of a kaolin suspension was investigated. The effects of different parameters, including pH, flocculant dosage, and initial turbidity on wastewater turbidity removal, was investigated. The results showed that a higher ratio of amine to CD-starch leads to a better amination reaction due to the greater availability of nitrogen for alkylation. Jar experiments showed that for initial turbidities of 50, 150 and 300 NTU, the appropriate doses of flocculant were 0.070, 0.085 and 0.130 mg/mL, respectively. For these initial turbidities, the maximum turbidity removal was achieved 80.1 %, 92 %, and 97.8 %, respectively. This work provides an innovative natural flocculant based on starch which can effectively treat turbid wastewaters., Competing Interests: Declaration of competing interest This study has been carried out under the financial support of the Sahand University of Technology., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Increasing resistance to antiviral drugs approved for the treatment of influenza urges the development of novel compounds. Ideally, this should be complemented by a careful consideration of the administration route. 6'siallyllactosamine-functionalized β-cyclodextrin (CD-6'SLN) is a novel entry inhibitor that acts as a mimic of the primary attachment receptor of influenza, sialic acid. In this study, we aimed to develop a dry powder formulation of CD-6'SLN to assess its in vivo antiviral activity after administration via the pulmonary route. By means of spray drying the compound together with trileucine, a dispersion enhancer, we created a powder that retained the antiviral effect of the drug, remained stable under elevated temperature conditions and performed well in a dry powder inhaler. To test the efficacy of the dry powder drug against influenza infection in vivo, infected mice were treated with CD-6'SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6'SLN was effective in mitigating the course of the disease compared to the control groups, reflected by lower disease activity scores and by the prevention of virus-induced IL-6 production. Our data show that CD-6'SLN can be formulated as a stable dry powder that is suitable for use in a dry powder inhaler and is effective when administered via the pulmonary route to influenza-infected mice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Stellacci is inventor on patent number WO 2018/015465 A1 − Virucidal compounds and uses thereof. Francesco Stellacci and Paulo H. Jacob Silva are co-founders of Asterivir, a start-up company that focuses on developing novel antivirals. The employer of Henderik W. Frijlink holds a license agreement with PureIMS on the Twincer and Cyclops dry powder inhalers. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; nor in the writing of the manuscript or in the decision to submit the article for publication., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The synergistic effects between xanthan gum (XG) and β-cyclodextrin (β-CD) on the properties and stability of vegetable oil-based whipped cream stabilized by kidney bean protein aggregates was investigated. The visual appearance, SEM, TEM, CLSM, FT-IR and LF-NMR results showed that when the ratio of XG to β-CD in the XG-β-CD complex was appropriate, the hydrogen bonding effect between β-CD and XG was significant enhanced, the three-dimensional network structure has the highest density, the emulsion droplets were the smallest and evenly distributed. The unique tapered microstructure of β-CD acted as a bridge between the hydrophilic and hydrophobic components, effectively preventing the aggregation of oil droplets and establishing a flexible support system between oil droplets; while the flexible molecular structure of XG could support Pickering emulsion system. The XG-β-CD complex had a synergistic effect with protein aggregates, making it ideal for use in whipped cream products. This study explored the stability mechanism of β-CD in the Pickering emulsion-based whipped cream system, providing valuable insights into producing whole plant-based whipped cream by texturizing highly unsaturated oils. This effectively solves the problem of inadequate intake of unsaturated oil for individuals who consume excessive amounts of animal-derived fats., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The feasibility of microwave heating to induce color/flavor changes of 4D printed white mushroom gel containing curcumin or γ-dodecalactone (γ-DDL) microcapsules was studied. Using gelatin/ β-cyclodextrin as wall material and soy protein isolate as emulsifier, microcapsules containing curcumin or γ-DDL were prepared by spray drying method. The microcapsules containing curcumin were mixed into white mushroom powder at different mass ratios (0, 0.1, 1, 3, 5 %, w/w) as printing ink. With the increase of microcapsule content, the viscosity, storage modulus and loss modulus of printing ink increased, but the water distribution and recovery performance did not change significantly. With the extension of heating time, the brightness value (L*) and the redness value (a*) of the printed sample increased, and the yellowness value (b*) decreased. After adding 3 % (w/w) microcapsules containing γ-DDL, the content change of the target flavor substance in the printed sample during microwave treatment was determined based on Gaschromatography-mass spectrometry (GC-MS). The results showed that microwave treatment could promote the release of flavor substances, and the content was 272.37 μg/kg when heated for 3 min. This study provides a new idea for the development of 4D printed food with special color and target flavor based on microcapsule technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diclofenac (DCF) is frequently detected in aquatic environments, emphasizing the critical need for its efficient removal globally. Here, we present the synthesis of Fe(III)-doped β-CD-grafted chitosan (Fe/β-CD@CS) cryogel beads designed for adsorbing DCF in aqueous solutions. The beads exhibited an average size of 2.94 ± 0.66 mm and a point of zero charge of 8.03. Adsorption experiments demonstrated that the Langmuir kinetic model provided the most accurate description of the kinetic data, while the Redlich-Peterson isotherm offered the best fit for the equilibrium data. The beads showcased a theoretical maximum adsorption capacity of 712.3 mg/g for DCF, with the adsorption process being identified as exothermic. DCF adsorption on the beads was attributed to hydrogen bonding, metal cation-π interactions, and electrostatic interactions. Reusability tests exhibited that the beads could be regenerated using 0.1 M NaOH. To perform deep learning modeling, adsorption experiments (n = 17), designed utilizing central composite design (CCD), were conducted in duplicate. The CCD framework incorporated input variables such as initial DCF concentration, adsorbent dosage, and solution pH, while the output variable was the DCF removal rate. Utilizing the adsorption data, an artificial neural network (ANN) model was constructed with a topology of 3: 7:10:1, featuring 3 input variables, 7 neurons in the first hidden layer, 10 neurons in the second layer, and 1 output variable. Employing the ANN model data, 3-D response surface plots were generated to elucidate the relationship between input variables and DCF removal rate. Additional adsorption tests were conducted to evaluate the developed ANN model, affirming its reliable predictability for the DCF removal rate. Analysis of the relative importance of the input variables revealed the following order of importance: solution pH (100 %) > adsorbent dosage (75.2 %) > initial DCF concentration (57.7 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stem cell-based therapies show promise for clinically addressing circumferential tracheal defects (CTD) through tissue engineering. However, creating a tissue-engineered tracheal tube possesses a healthy cartilage matrix and intact tube structure remains a challenge. A solution lies in the use of an injectable hydrogel with shape adaptability and chondrogenic capacity, serving as a practical and dependable platform for tubular tracheal cartilage regeneration. In this study, we developed an injectable hydrogel using modified natural polymers-hydrazide-grafted gelatin (Gelatin-ADH) and aldehyde-modified hyaluronic acid with sulfated groups (HA-CHO-SO 3 ) via Schiff Base interaction. Additionally, aldehyde-modified β-cyclodextrin (β-CD-CHO) was introduced into the network during hydrogel formation. The negative sulfated groups and hydrophobic cavities of β-cyclodextrin facilitated the efficient encapsulation and sustained release of transforming growth factor-β1 (TGF-β1) and kartogenin (KGN) within our hydrogel. This synergistically promoted the chondrogenesis of loaded bone marrow stem cells (BMSCs). Subsequently, we employed this TGF-β1, KGN, and BMSCs loaded hydrogel to form a cartilage ring. This ring was then assembled into an engineered tracheal cartilage tube using our previously reported ring-to-tube strategy. Our results demonstrated that the engineered tracheal cartilage tube effectively repaired CTD in a rabbit model. Hence, this study introduces a novel hydrogel with significant clinical application potential for tracheal tissue engineering., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The dynamic combination of aromas and cyclodextrins is an important means to achieve their stability and controllability, and accurately revealing their interaction rules is the key to designing and constructing high-quality aroma nanocarriers. In this study, the inclusion mechanism between alcohol aroma compounds with different structures and β-cyclodextrin (β-CD) was studied by combining molecular dynamics simulation and experimental methods. Results showed that the selected alcohol aroma compounds formed inclusion complexes (ICs) with β-CD in a 1:1 ratio, while alcohol aroma compounds containing cyclic structures were more tightly bound to β-CD. Van der Waals forces were the primary forces driving the formation and stabilization of the ICs. Cinnamyl alcohol/β-CD ICs showed the most significant antimicrobial effect and notably prolonged the shelf life of strawberries. This study aimed to provide theoretical support for precisely designing and preparing highly stable flavours and fragrances, as well as expanding their application range., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Blueberries are highly susceptible to fungal pathogens and oxidative deterioration due to their thin epidermal layer, which can be mitigated by applying a natural polymer-based antimicrobial coating to their surface. This study aimed to develop a chitosan/gelatin-based antimicrobial coating utilizing ginger essential oil (GEO) to extend the postharvest quality of blueberries. To ensure GEO's stability within the coating, it was initially encapsulated with β-cyclodextrin (β-CD) using the inclusion complexation technique. The GEO/β-CD inclusion complex (IC) formed rhomboidal shapes with high encapsulation efficiency and small particle sizes. When the optimized GEO/β-CD IC was incorporated into the chitosan/gelatin polymer solution, it significantly increased surface hydrophobicity and free radical scavenging activity, and suppressed the growth of three selected fungi, namely Botrytis cinerea, Penicillium italicum and Alternaria alternaria. The results of postharvest storage quality revealed that blueberry samples coated with CH/Gel-GEO/β-CD IC-5 effectively maintained the quality of blueberries by decreasing weight loss and decay incidence, and regulating anthocyanin and other oxidation-related enzyme activities compared to the control group during 16 days at 25 °C and 40 days at 4 °C storages. In conclusion, it can be stated that CH/Gel-GEO/β-CD composite coating can be a promising technology to address the drawbacks of blueberry preservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nasal systemic drug delivery may provide an easy way to substitute parenteral or oral dosing, however, the excipients have an important role in nasal formulations to increase the permeability of the mucosa and prolong the residence time of the drug. In this work, we aimed to produce meloxicam potassium monohydrate (MXP) containing nasal powders by a nano spray drier with the use of a neutral, an anionic and a cationic β-cyclodextrin as permeation enhancers, and (polyvinyl)alcohol (PVA) as a water soluble polymer. The following examinations were performed in order to study the effect of the applied excipients on the nasal applicability of the formulations: laser scattering, scanning electron microscope measurement, XRPD, DSC and FTIR measurements, adhesivity, in vitro drug release and permeability tests through an artificial membrane and RPMI 2650 cells. Based on our results, spherical particles were prepared with a size of 1.89-2.21 µm in which MXP was present in an amorphous state. Secondary interactions were formed between the excipients and the drug. The charged cyclodextrin-based formulations showed significantly higher adhesive force values regardless of the presence of PVA. The drug release was fast and complete. The passive diffusion of MXP was influenced not only by the charge of the cyclodextrin, but the presence of PVA, too. The permeation of the drug was enhanced in the presence of the anionic cyclodextrin testing it on RPMI 2650 cell model., (Copyright © 2024. Published by Elsevier B.V.)

Baicalein, a flavone derived from Scutellaria baicalensis Georgi, exhibits potent anti-inflammatory, antiviral, and anticancer properties. Its derivative, known as 8-bromobaicalein (BB), has been found to have strong cytotoxic effect on MCF-7 human breast cancer cells. However, its limited solubility in water has hindered its potential for wider applications. To address this issue, we investigated the use of cyclodextrins specifically βCD, 2,6-di-O-methyl-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) to improve the solubility of BB through inclusion complexation. During 250 ns molecular dynamics simulations, it was found that BB can form inclusion complexes with all βCDs. These complexes exhibit two distinct orientations: chromone group insertion (C-form) and phenyl group insertion (P-form). The formation of these complexes is primarily driven by van der Waals interactions. DMβCD has the highest number of atom contacts with BB and the lowest solvent accessibility in the hydrophobic cavity. These results coincide with the highest binding affinity from the MM/GBSA-based free energy calculation method. Experimental phase solubility diagrams revealed a 1:1 stoichiometric ratio (A L type) between BB and βCDs, in which BB/DMβCD showed the highest stability. The formation of inclusion complexes was confirmed by differential scanning calorimetry and scanning electron microscope methods. Additionally, the BB/DMβCD inclusion complex demonstrated significantly higher anticancer activity against MCF-7 human breast cancer cells compared to BB alone. These findings underscore the potential of DMβCD for formulating BB in pharmaceutical and medical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate ( EPPP ), and its 1:1 complex with β-cyclodextrin ( EPPPβCD ) have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of EPPPβCD in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of EPPPβCD on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4 + CD25 + fractions at the onset of inflammation. This effect is attributed to the inhibition of Treg proliferation, which is crucial in hastening the resolution of inflammation. These findings underscore the potential of EPPPβCD as a promising therapeutic agent in controlling and mitigating inflammation mediated by heavy metal exposure, thereby offering a new avenue for the development of anti-inflammatory treatments.

Cell membrane-coated nanoparticles (CNPs) have emerged as an attractive nanomedical tool. The basic premise is that the surface properties of natural cells can be integrated with the physical and chemical properties of nanoparticles by coating them with cell membranes. However, the degree of preservation of membrane proteins on nanoparticles, a key indicator related to the biomedical function of these biomimetic systems, is largely affected by the coating process. Herein, we report a supramolecular cell membrane conjugation strategy mediated by host-guest interactions to assemble CNPs without compromising protein activities. β-cyclodextrin (β-CD) was rapidly and stably inserted into the cell membrane by a lipid anchor without affecting the function of membrane proteins, thus attaching host-guest sites to the membrane surface. By harnessing the excellent binding affinity between β-CD attached to the membrane surface and adamantane, a supramolecular cell membrane-magnetic nanoparticle conjugate (CDM@AMNPs) was synthesized. Thanks to the nondestructive assembly of this strategy, CDM@AMNPs were endowed with a greater number of active binding sites, exhibiting efficient adsorption performance. This supramolecular conjugation strategy mediated by nonreceptor site-based host-guest interactions proposes a scalable and cell-friendly strategy for the development of highly efficient CNPs.

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and β-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities.

Dimenhydrinate (DMH), used to alleviate motion sickness symptoms such as nausea, vomiting, dizziness, and vertigo, encounters limitations in oral pharmaceutical formulations due to its poor water solubility and bitter taste. Our research hypothesized that inclusion complexation with β-cyclodextrin (β-CD) might address these drawbacks while ensuring that the newly formed complexes exhibit no cytotoxic or genotoxic effects on peripheral blood mononuclear cells (PBMCs). Inclusion complexes were prepared using the kneading method and the solvent evaporation method. The phase solubility analysis, attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC) were conducted to evaluate the complexation efficacy and stability constant of the new binary systems. The results demonstrated that both methods provided complete and efficient complexation. Cytogenotoxic analysis, including the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline comet assay, and cytokinesis-block micronucleus cytome (CBMN-cyt) assay, was conducted to assess the cytogenotoxic potential of DMH-β-CD inclusion complexes, a topic previously unexamined. No cytotoxic or genotoxic effects were observed within the concentration range of 36.36 to 109.09 ng/mL. Cell viability of treated PBMCs exceeded 85% for all tested concentrations. No significant increases in DNA strand breaks were observed at any dose, and tail intensity of all complexes remained lower or up to 2.2% higher than the negative control. Parameters indicating genotoxic effects, as well as cytotoxic and cytostatic potential in the CBMN-cyt assay, did not significantly differ from untreated controls. These results suggest that inclusion complexation with β-CD might be a safe and promising solution to overcome the limitations of poor solubility and unpleasant taste of DMH, potentially providing opportunities for new and improved oral pharmaceutical dosage forms.

This study involves synthesizing peanut hull hydrochar (PHH) and a PHH/β-CD/Fe 3 O 4 magnetic composite through hydrothermal and chemical precipitation methods, respectively, to use as effective adsorbents for Pb 2+ removal. Vibrating-sample magnetometry (VSM) and Brunauer-Emmett-Teller (BET) analyses revealed that the magnetic saturation value and specific active surface area of PHH/β-CD/Fe 3 O 4 are 31.543 emu/g and 32.123 m 2 /g, respectively. The impact of key variables on adsorption efficiency was evaluated using the response surface method - central composite design. ANOVA results (F-value: 166.22 and p-value: <0.05) demonstrated that the model effectively assesses the interaction of variables in the adsorption process. Additionally, R 2 , Adjusted R 2 , and Predicted R 2 values were 0.999, 0.986, and 0.975, respectively, indicating the model's high adequacy in describing response changes. The maximum efficiency for Pb 2+ adsorption was found to be 95.35% using PHH and 99.73% with the PHH/β-CD/Fe 3 O 4 magnetic composite. These measurements were taken at a temperature of 25 °C, an adsorbent dose of 1 g/L, a pH of 6, and a Pb 2+ concentration of 5 mg/L, with respective contact times of 130 min and 50 min. Thermodynamic analysis revealed negative enthalpy and Gibbs free energy values, indicating that the adsorption process is exothermic and spontaneous. The negative entropy parameter suggests a reduction in random interactions during the process. The Pb 2+ adsorption data for both PHH (R 2 : 0.982) and PHH/β-CD/Fe 3 O 4 (R 2 : 0.985) were best described by the Pseudo 2nd order kinetic model. Equilibrium data followed the Freundlich model, with R 2 values of 0.981 for PHH and 0.990 for PHH/β-CD/Fe 3 O 4 , highlighting the importance of heterogeneous surfaces in the removal process. The maximum adsorption capacities for Pb 2+ were 26.72 mg/g for PHH and 33.88 mg/g for PHH/β-CD/Fe 3 O 4 . Reuse and stability tests confirmed the structural stability and reusability of the adsorbents. Therefore, the PHH/β-CD/Fe 3 O 4 magnetic composite is a promising option for removing Pb 2+ from aqueous solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of β-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (β-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS). Moreover, the glucose oxidase (GOx) was loaded through electrostatic adsorption, which efficiently restricts the energy supply in tumor tissues, thus enhancing the therapeutic efficacy of SDT for tumors. Under optimal conditions, the entire system exhibited favorable water solubility, suitable particle size and viable biocompatibility. This facilitated the integration of the characteristics of starvation therapy and sonodynamic therapy, resulting in efficient inhibition of tumor growth with minimal side effects in vivo. This work may provide new insights into the application of natural oligosaccharides for construct multifunctional nanocarrier systems, which could optimize the design and development of sonodynamic therapy strategies and even combination therapy strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA), an endocrine disruptor, is widely used in food packaging materials, including drink containers. Sensitive detection of BPA is crucial to food safety. Herein, we have developed a novel optical-driven hydrogel film sensor for sensitive BPA detection based on the displacement of spiropyran (SP) from β-cyclodextrin (β-CD) cavity by BPA followed by the photochromism of the released SP. The released SP converts to the ring-opened merocyanine form which shows an enhanced red fluorescence in the dark. The sensor demonstrates a linear detection range from 0.1 to 20 μg mL -1 with a limit of detection at 0.027 μg mL -1 and a limit of quantification at 0.089 μg mL -1 . Notably, the proposed β-CD/SP hydrogel can be reused due to the reversible isomerization of SP and the reversible host-guest interaction. This sensor also shows good performance for BPA determination in real samples, indicating its great potential for food safety monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This research develops diacylglycerol (DAG) based Pickering emulsions with enhanced oxidative stability stabilized by self-assembled quercetin/DAG/β-cyclodextrin (β-CD) complexes (QDCCs) using a one-step agitation method. Influence of DAG content (5%, 15%, 40%, and 80%, w/w) on the self-assembly behavior, interfacial properties, and emulsifying ability of complex particles was investigated. SEM, XRD and ATR-FTIR studies confirmed the formation of ternary composite particles. QDCCs in 80% DAG oil had the highest quercetin encapsulation efficiency (6.09 ± 0.01%), highest DPPH radical scavenging rate and ferric reducing antioxidant property (FRAP). β-CD and quercetin adsorption rates in emulsion with 80% DAG oil were 88.4 ± 2.53% and 98.34 ± 0.15%, respectively. Pickering emulsions with 80% DAG had the smallest droplet size (8.90 ± 1.87 μm) and excellent oxidation stability. This research develops a novel approach to regulate the physicochemical stability of DAG-based emulsions by anchoring natural antioxidants at the oil-water interface through a one-pot self-assembly method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Acurate and sensitive determination of hazards from food contact materials is important to monitor food safety. It is necessary to excavate efficient adsorbent for simultaneous recognition and adsorption of food hazards of trace level for sample preparation. In this work, β-cyclodextrin and calix[4]arene were employed as hybrid functional monomers to prepare macrocyclic porous organic polymer (β-CD-CX4 POP). It was proved that the supramolecular cavities of β-CD-CX4 POP could form inclusion complexes with fluorescent whitening agents (FWAs) through host-guest recognition, which greatly improved the adsorption performance. The hydrophobic cavities of β-cyclodextrin and calix[4]arene of β-CD-CX4 POP exhibited synergistic effect for simultaneous recognition of FWAs. The high-throughput enrichment of FWAs was realized by β-CD-CX4 POP membranes coupled with a multiple-channel syringe pump. Based on membrane-based solid-phase extraction combined with UHPLC-MS/MS, a sensitive analytical method was established to determine six FWAs. The LODs was in range of 3-50 ng/L with the linear range of 0.02-100 μg/L. The developed method was used to quantify FWAs in bread wrapper and bread, and the spiked recoveries ranged from 78.1%-119% with RSD of 2.3%-9.7%. This work indicated that β-CD-CX4 POP was promising for the simultaneous recognition and adsorption of FWAs migrating from food contact materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Laser-induced graphene (LIG) possesses characteristics of easy handling, miniaturization, and unique electrical properties. We modified the surface of LIG by electropolymerizing β-cyclodextrin (β-CD), which was used to immobilize antibodies on the electrode surface for highly sensitive detection of targets. N 6-methyladenosine (m6A) is the most prevalent reversible modification in mammalian messenger RNA and noncoding RNA, influencing the development of various cancers. Here, β-CD was electropolymerized to immobilize the anti-m6A antibody, which subsequently recognized the target m6A. This was integrated into the catalytic hydrogen peroxide-hydroquinone (H 2 O 2 -HQ) redox system using phos-tag-biotin to generate electrochemical signals from streptavidin-modified horseradish peroxidase (SA-HRP). Under optimal conditions, the biosensor exhibited a linear range from 0.1 to 100 nM with a minimum detection limit of 96 pM. The method was successfully applied to the recovery analysis of m6A from HeLa cells through spiking experiments and aims to inspire strategies for point-of-care testing (POCT).

6-mercaptopurine (6-MP) is widely used in the treatment of many diseases, but exhibits some serious side effects due to its toxicity. Therefore, it is important and imperative to effectively control and monitoring concentration of 6-MP. Herein, we designed a smartphone-assisted colorimetric sensing platform for 6-MP detection, based on an excellent β-cyclodextrin modified MnO 2 nanosheets (β-CD@MnO 2 NNS) mediated oxidase-like activity. β-CD@MnO 2 NNS can directly oxidizes 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB with color changes, yielding more than 3-fold higher oxidase-like catalytic activity compared with individual MnO 2 NNS. After adding 6-MP, β-CD@MnO 2 NNS can be reduced to Mn 2+ and lose their oxidase-like properties, resulting in a color and absorbance change for sensitive and selectivity detection of 6-MP. Meanwhile, the smartphone-based color recognition application can intuitively and simply measure the concentration of 6-MP. The limits of detection UV-vis instrument and smartphone were 0.35 μM and 0.86 μM, respectively. This method has also been successfully applied to the detection of real samples. Finally, this study provides a new promising platform for detection of 6-MP and is expected to be used in application of pharmaceutical analysis and biomedicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, β, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, β-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with β-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with β-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with β-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage., (© 2024. The Author(s).)

The excessive accumulation of heavy metals has adverse effects on the human body. Here, magnetic iron oxide-impregnated carboxymethyl-β-cyclodextrin was synthesized. The synthesized material was employed as a magnetic solid-phase extracting adsorbent for specific heavy metals like lead (Pb), nickel (Ni), copper (Cu), and cobalt (Co). Characterization was performed by X-ray diffraction, energy dispersive X-ray spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller, and Fourier-transform infrared spectroscopy. The analytical merits, like detection limits (Pb: 1.38 ng/mL, Ni: 0.5 ng/mL, Co: 0.14 ng/mL, and Cu: 0.55 ng/mL) and quantification limits (Pb: 4.14 ng/mL, Ni: 1.62 ng/mL, Co: 1.85 ng/mL, and Cu: 1.82 ng/mL) were calculated. Similarly, the preconcentration and enhancement factors (15) and relative standard deviation (Pb: 3.5, Ni: 0.92, Co: 2.7, and Cu: 1.5) were also calculated. The interfering study shows that the method is highly selective. For validation, it was applied to certified reference materials such as the Institute of Nuclear Chemistry and Technology ornamental Basma tobacco leaves and trace metal double addition 63.4 environmental water with good percent recovery values (92%-99%). Real water and food samples were also used with satisfactory (90%-99%) recovery results., (© 2024 Wiley‐VCH GmbH.)

Purpose: Insomnia is a major health concern, and melatonin (MLT) is key for initiating sleep. Delivering MLT nasally can enhance brain bioavailability by targeting the olfactory region. This study aimed to fabricate MLT embedded microparticles for nasal delivery., Methods: MLT-cyclodextrin (CD) derivatives complex microparticles (MCCMPs) were fabricated by spray drying and spray freeze drying MLT and CD derivative solutions. Phase solubility and 1 H- 1 H ROSEY NMR analysis assessed MLT-CD assembly. The effects of formulation compositions and process parameters on microparticle structural attributes were investigated. The in vitro nasal release and deposition performances were evaluated by a modified paddle-over-disk apparatus and 3D-printed nasal cavity cast, respectively., Results: Sodium sulphobutylether-β-cyclodextrin (SBE-β-CD) exhibited the best complexation ability with MLT, with the indole structure of MLT included in its cavity. Spray dried MCCMPs showed dense structure with high density, while the spray freeze dried counterpart showed the brittle and porous structure with low density. Despite the porous structure may promote the release rate of spray freeze dried samples, the high hydrophilicity of the CD derivative overshadows this advantage. Samples prepared by spray drying not only exhibited rapid release rates but also could deposit more effectively in the olfactory region, as they avoid breakage due to their higher mechanical strength. The optimal sample showed ~ 86.70% of the MLT released at 20 min and ~ 10.57% of the deposition fraction in the olfactory region., Conclusions: This work compares MCCMPs fabricated by spray drying and spray freeze drying, providing the optimal formulation and process combinations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction. Tissue conditioners modified with antifungals are a potential alternative to denture stomatitis (DS) treatment. Gap Statement. Information on tissue response to this treatment before its clinical application is lacking. Aim. This study aimed to evaluate the tissue response of a tissue conditioner modified with antifungals in a rat model of DS. Methodology. After DS induction for 4 days under antibiotic therapy, Wistar rats had their intraoral devices (IODs) relined with the tissue conditioner Softone without (Soft) or with the MICs against Candida albicans of nystatin (Nys) or chlorhexidine (Chx) complexed or not with β-cyclodextrin (Nys:βCD and Chx:βCD). Three controls were included: healthy rats [negative control (Nc)], rats using a sterile IOD [sterile device (Sd)] and rats with DS that did not receive treatment (DS). After 4 days of treatment, the palatal mucosa under the IODs underwent histological processing for morphohistopathological and histometric analyses, morphology of collagen fibres (birefringence), immunohistochemistry for the expression of cell proliferation (proliferating cell nuclear antigen) and cytokine (IL-1β). Results. The Nc and Sd groups were similar ( P >0.05), displaying epithelial and connective tissues without any discernible changes in the parameters assessed. The DS and Soft groups exhibited pronounced epithelial alterations, cell proliferation and expression of the cytokine IL-1β. In groups treated with drug incorporation (Nys, Chx, Nys:βCD and Chx:βCD), all samples demonstrated a reduction in tissue inflammation or complete tissue recovery, with an epithelium compatible with health. For the immunohistochemical parameters, the Chx, Nys:βCD and Chx:βCD groups were comparable with Nc ( P >0.05). Conclusion. The proposed treatment could be promising for DS, as it led to the tissue recovery of the palatal mucosa. Nevertheless, much lower concentrations of complexed antifungals were required to achieve a similar or higher degree of tissue response compared with uncomplexed drugs in a modified tissue conditioner formulation.

This study introduces a remarkably simple, green, and highly sensitive inclusion complex based spectrofluorimetric method for analyzing two sodium glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (EGF) and dapagliflozin (DGF). The method utilizes beta-cyclodextrin (β-CD) complexation to enhance the native fluorescence of EGF and DGF in aqueous solutions, resulting in 11.0-fold and 9.0-fold intensity increases, respectively. Fluorescence measurements were conducted at 301 nm emission following 230 nm excitation for both drugs. The method demonstrates excellent linearity (0.9994 for EGF and 0.9993 for DGF) over concentration ranges of 5.0-250.0 ng/mL and 10.0-300.0 ng/mL, with low detection limits of 1.05 and 1.38 ng/mL for EGF and DGF, respectively. The method's versatility was validated through successful application in pharmaceutical formulations, content uniformity testing, and biological fluids. This eco-friendly approach primarily uses water as a solvent and requires minimal reagents. The method's environmental impact was comprehensively evaluated using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE)., (© 2024 John Wiley & Sons Ltd.)

A novel biocomposite (FPPW-β-CD) was prepared by a simple and sustainable method involving fine potato peel waste, β-cyclodextrin (β-CD), and green citric acid through the crosslinking reaction. The polymer was characterized using SEM, FTIR, XRD, TGA, and DSC analyses. The adsorbent performance was evaluated about the glyphosate and diuron adsorption from the aqueous solution. Pesticide removal was investigated regarding the influence of solution pH, temperature, and initial concentration of contaminants. Also, it highlights the main interactions involved in the adsorption phenomenon based on the pH effect and characteristics of adsorbent and adsorbate molecules. The maximum adsorption capacity values according to the Sips model were higher than 2000 µg g -1 . The pseudo-second-order and general-order models described the kinetic data well. Thermodynamic parameters indicated that pesticide removal was spontaneous and favorable. The magnitude of enthalpy variation values (27.37 kJ mol -1 and - 100.79 kJ mol -1 ) revealed that the glyphosate and diuron adsorption occurred through the physisorption and chemisorption, respectively. The novel biocomposite is a promising green adsorbent for the uptake of micropollutant pesticides in aqueous solutions at concentrations of µg L -1 ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pomegranate peel polyphenols (PPPs) are recognized as promising food additives due to their diverse bioactivities; however, their application is limited by poor stability. To address this critical issue, three types of PPPs microcapsules were prepared using β-cyclodextrin (CD), whey protein isolate (WPI), and a composite material of CD-WPI through ultrasound treatment (US). Results revealed that ultrasound treatment can enhance the PPPs-wall material interaction, as evidenced by MD simulations. The encapsulation efficiency of CD-WPI-PPPs was 93.73 %, which was significantly higher than that of CD-PPPs and WPI-PPPs (p < 0.05). The degradation rate constant of CD-WPI-PPPs was reduced by 95.83 %, and its t 1/2 was extended by 23-fold compared to that of unencapsulated PPPs. Furthermore, CD-WPI-PPPs exhibited greater DPPH scavenging activity and inhibited polyphenol release during oral and gastric digestion while promoting release during intestinal digestion. These outcomes were attributed to enhanced integrity and interactions between PPPs and composite materials in the microcapsules formed through ultrasound treatment, as supported by SEM images and FT-IR spectra. Consequently, the application of US in the preparation of PPPs microcapsules presents a promising strategy for developing natural nutrient additives for food applications, thereby enhancing the functional properties of food products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Considering that fruits are vulnerable to damage and waste during stockpiling, transport and marketing. Given this, an innovative curcumin inclusion compound (Cur@β-CD) was devised in this study to introduce oil-soluble curcumin (Cur) into water-soluble polyvinyl alcohol (PVA) materials, thereby fabricating food packaging films endowed with excellent properties. DPPH test manifested that the oxidation resistance for PCOMC-Cur@β-CD film was 95 % above PVA material. It was ascribed to the fact that the Cur@β-CD elevated the water solubility of Cur while the increase of water solubility heightened the antioxidant effect for Cur in the film. Additionally, the chitosan (CS) was crosslinked with malic acid (MA), which elevated the barrier property of the film, reduced the amount of oxygen transmission and further retarded the oxidation reaction of the fruits for packaging. The antibacterial test demonstrated that the antibacterial rates of PCOMC-Cur@β-CD film against E. coli and S. aureus reached 92 % and 95 %, respectively, which was attributed to the slow release of Cur when Cur@β-CD was dissolved in PVA material and the Schiff base reaction between Cur and amino groups on CS. These findings indicate that the PCOMC-Cur@β-CD film developed in this work can provide certain insights into the field of food packaging., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was -5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.

The present study investigates the utilization of a supramolecular deep eutectic solvent (SUPRADES), consisting of sulfated-β-cyclodextrin (S-β-CD) and citric acid (CA), as a chiral selector (CS) in capillary electrophoresis for the enantiomeric separation of nefopam (NEF) and five cathinone derivatives (3-methylmethcathinone [3-MMC], 4-methylmethcathinone [4-MMC], 3,4-dimethylmethcathinone [3,4-DMMC], 4-methylethcathinone [4-MEC], and 3,4-methylendioxycathinone [MDMC]). A significant improvement in enantiomeric separation of the target analytes was observed upon the addition of S-β-CD-CA to the background electrolyte (BGE), leading to a baseline separation of all analytes. In particular, the optimum percentage of S-β-CD-CA, added to the BGE, was determined to be 0.075% v/v for NEF (R s  = 1.5) and 0.050% v/v for three out of five cathinone derivatives (R s  = 1.5, 1.6, and 2.4 for 3-MMC, 4-MEC, and 3,4-DMMC, respectively). In the case of 4-MMC and MDMC, a higher percentage of the CS, equal to 0.075% and 0.10% v/v, respectively, was required to achieve baseline separation (R s  = 1.5, 1.9 for MDMC and 4-MMC, respectively). The outcomes of the present study highlight the potential effectiveness of using SUPRADES as a CS in electrophoretic enantioseparations., (© 2024 The Author(s). Electrophoresis published by Wiley‐VCH GmbH.)

The study investigated the influence of additives on the fabrication of mixed matrix membranes comprising polyethersulfone (PES), with a specific focus on hydrophilicity, flux, morphology, and antifouling properties. Carboxymethyl modified β-cyclodextrin (CMβ-CD) was used to enhance the dispersion and hydrophilicity of graphene oxide (GO), leading to the formation of a hydrophilic and stable composite nanoparticle (CMCD@GO). The hydrophilicity (WCA <51.5°) and water flux (32.6 L m -2. h -1 ) of the modified PES membranes (MCDGO-x) were improved by the incorporation of CMCD@GO nanoparticles, while that of PES membrane was 79.7° and 10.6 L m -2. h -1 . The rate of backscattered light intensity (ΔBS) of MCDGO-x suspensions remains stable, suggesting stable dispersion of CMCD@GO in organic solvents. Compared to the bare PES membrane, the MCDGO-x membrane exhibits a thinner active layer and a finger-like structure. The MCDGO-x membrane exhibited excellent naphthenic acids (NAs) rejection (>93.2%) due to reduced roughness and higher hydrophilicity, while the GO-modified PES membrane (MGO-5) exhibited lower NAs rejection (87.2%). Furthermore, the MCDGO-5 membrane showed higher flux recovery ratio (FRR) of 79.3% compared to MGO-5 membrane (68.5%) after three cycles, indicating the antifouling performance of MCDGO-x for NAs was significantly improved. The combination of CMβ-CD and GO enhance the flux and antifouling properties of PES ultrafiltration membranes, suggesting significant potential for applications in the purification of oil sands process water and the treatment of oily wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with β-cyclodextrin (βCD) and its three analogs, dimethyl-β-cyclodextrin (DMβCD), hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4',6'-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with βCDs through two distinct orientations, with OXY/SBEβCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEβCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEβCD (2060 M -1 ), HPβCD (1860 M -1 ), DMβCD (1700 M -1 ), and βCD (1420 M -1 ). All complexes exhibited a 1:1 binding mode (A L type), with SBEβCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1 H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMβCD, OXY/HPβCD, and OXY/SBEβCD were markedly superior compared to that of OXY alone., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, a double-layer active and intelligent packaging system was developed based on two main natural macromolecules i.e. protein and carbohydrate with green perspective. Firstly, the salep-based films containing different concentrations (0-8 % w/w) of the inclusion complex of β-cyclodextrin/black chickpea anthocyanins (βCD/BCPA) were produced. The salep film containing 8 % of βCD/BCPA complex was specified as the optimized film sample based on its performance as a color indicator. The electrospinning of black chickpea protein isolate nanofibers (BCPI NFs) containing citral nanoliposomes (NLPs) was done on the optimized salep film. The cross-sectional field emission scanning electron microscopy approved the creation of double-layer structure of the developed film. The study of chemical and crystalline structure, as well as the thermal properties of the film exhibited the physical attachment of BCPI electrospun NFs on salep film. The effectiveness of the developed system was studied in detection of spoilage and increasing the shelf life of seafood products, including shrimp and fish fillet. The performance of the intelligent layer in detection of freshness/spoilage was acceptable for both seafood products. In addition, the active layer of the film controlled the changes of pH, total volatile basic nitrogen, oxidation, and microbial load in samples during storage time., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The incorporation of active compounds into polymeric matrices using traditional methods has several drawbacks mainly due to the high volatility and thermal sensitivity of these substances. A solution to this problem could be the incorporation of bioactive compounds forming inclusion complexes as a strategy to improve the chemical stability, bioactivity and achieve controlled release. In this work, β-cyclodextrin/carvacrol inclusion complex was prepared by spray drying to be incorporated into poly(lactic acid) (PLA) and Mater-Bi® films by supercritical CO 2 impregnation. The impregnation process was carried out at pressures of 10, 15 and 20 MPa and at 40 °C. Both polymers showed the highest amount of incorporated inclusion complex at 15 MPa, where the percentage of impregnation varied from 0.6 % to 7.1 % in Mater-Bi® and PLA, respectively. Release tests for PLA films impregnated with inclusion complex showed a slow release of the active compound, which did not reach equilibrium after 350 h under the experimental conditions. This prolonged release was not observed in Mater-Bi® due to the lower incorporation of the inclusion complex. The release rate was described herein by a comprehensive phenomenological model considering the decomplexation kinetics combined with the equilibrium and mass transfer expressions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

To reduce environmental pollution and improve human health, developing green active food packaging materials is very necessary. In this study, a novel antioxidant and antibacterial composite film was produced by incorporating inclusion complex (CDIC) of cannabidiol (CBD) with 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) into pectin. The pectin films loaded with CBD and hemp leaf water extract (HLE) were prepared for comparison. Comprehensive characterizations showed CBD was encapsulated by DM-β-CD and CDIC was evenly dispersed into pectin matrix, forming the compact and intact film. The composite films showed good mechanical properties and biodegradability. CDIC film showed the highest transparency and smoothness (Rrms/Rmax: 2.6/16.8 nm). The addition of bioactives reduced the water-binding capacity and CDIC film had the strongest hydrophobicity. Besides, DM-β-CD encapsulation improved the thermal stability of CBD in CDIC film. Benefiting from encapsulation and excellent bioactivities of CBD, CDIC film showed excellent antioxidant capacity and antibacterial activity, effectively inhibiting colony growth and maintaining the strawberry color in strawberry preservation. This work could provide a novel eco-friendly candidate for food packaging material and expand the use of CBD in food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide β-cyclodextrin (β-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/β-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at ∼1740 cm -1 , related with collagen crosslinking. Higher β-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The β-CD content directly influenced the morphology and semi-crystallinity. All Col/β-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than β-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/β-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.

The objective of this work was to design a new drug nanoparticle (NP) composed of chitosan/β-cyclodextrin/sodium tripolyphosphate/alginate (CS/βCD/TPP/AL) loaded with a clove extract (CE) for potential anticancer effects. The extract was prepared by two extraction methods: hydroalcoholic maceration (MAC) with 80% MeOH and supercritical fluid (SCF). The MACCE and SCFCE CE NPs had particle sizes of 71 nm and 20 nm, respectively with irregular spherical shapes. The nanocarriers achieved entrapment efficiencies of over 90%. MACCE-NPs and SCFCE-NPs released 18.35% and 10.12% of the extract after 6 h, respectively. Cell viability decreased to 54%, 7%, and 12% in HeLa, U87, and KB cell lines, respectively, after a 48-hour treatment with SCFCE-NPs and 75%, 8%, and 17% after treatment with MACCE-NPs, significantly reduced compared to the control. It is concluded that NPs containing CE exhibit a higher degree of toxicity due to better penetration into cells.