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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

[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]

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]

The inclusion complexes of α-, β-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin with two amino acid stereoisomers (L-, D-arginine and L-, D-histidine) were studied by using differential scanning calorimetry, thermogravimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy methods. The solid inclusion compounds were prepared in a 1:1 molar ratio of the host and guest using the co-precipitation method. The pH measurements and structural visualization of complexes were carried out. The obtained results proved the formation of the complexes and revealed that the size and the symmetry of the cyclodextrin (CD) and also the structure and flexibility of the amino acid molecule had a significant influence on the complexation interaction. The correlation of the experimental data shows that βCD has a preference to form more stable complexes with levogir isomers of amino acid than αCD and 2- hydroxypropyl-α-cyclodextrin. The complexation of the amino acids isomers was accomplished by partial inclusion of the guest molecule in the CD cavity, and it was observed that CDs could better discriminate between histidine isomers than between arginine isomers. [ABSTRACT FROM AUTHOR]

The presence of a chiral or chirally perturbed chromophore in the molecule under investigation is a fundamental requirement for the appearance of a circular dichroism (CD) spectrum. For native and for most of the substituted cyclodextrins, this condition is not applicable, because although chiral, cyclodextrins lack a chromophore group and therefore have no characteristic CD spectra over 220 nm. The reason this method can be used is that if the guest molecule has a chromophore group and this is in the right proximity to the cyclodextrin, it becomes chirally perturbed. As a result, the complex will now provide a CD signal, and this phenomenon is called induced circular dichroism (ICD). The appearance of the ICD spectrum is clear evidence of the formation of the complex, and the spectral sign and intensity is a good predictor of the structure of the complex. By varying the concentration of cyclodextrin, the ICD signal changes, resulting in a saturation curve, and from these data, the stability constant can be calculated for a 1:1 complex. This article compares ICD and NMR spectroscopic and molecular modeling results of cyclodextrin complexes of four model compounds: nimesulide, fenbufen, fenoprofen, and bifonazole. The results obtained by the different methods show good agreement, and the structures estimated from the ICD spectra are supported by NMR data and molecular modeling. [ABSTRACT FROM AUTHOR]

High-harmonic spectroscopy is an all-optical technique with inherent attosecond temporal resolution that has been successfully employed to reconstruct charge migration, electron-tunneling dynamics, and conical-intersection dynamics. Here, we demonstrate the extension of two key components of high-harmonic spectroscopy, i.e., impulsive alignment and measurements with multiple driving wavelengths to 1,3-cyclohexadiene and benzene. In the case of 1,3-cyclohexadiene, we find that the temporal sequence of maximal and minimal emitted high-harmonic intensities as a function of the delay between the alignment and probe pulses inverts between 25 and 30 eV and again between 35 and 40 eV when an 800-nm driver is used, but no inversions are observed with a 1420-nm driver. This observation is explained by the wavelength-dependent interference of emission from multiple molecular orbitals (HOMO to HOMO-3), as demonstrated by calculations based on the weak-field asymptotic theory and accurate photorecombination matrix elements. These results indicate that attosecond charge migration takes place in the 1,3-cyclohexadiene cation and can potentially be reconstructed with the help of additional measurements. Our experiments also demonstrate a pathway toward studying photochemical reactions in the molecular frame of 1,3-cyclohexadiene. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the physico-chemical and biological properties of cyclodextrin-based polymers by the example of interaction with human serum albumin, erythrocytes, and bacteria to understand the prospects of their application as drug delivery systems. We synthesized polymers based on one of cyclodextrin derivatives with nonpolar (-CH3) or polar (-CH2CH(OH)CH3) substituents by crosslinking with 1,6-hexamethylene diisocyanate or succinic anhydride. The polymers form particles with an average size of ~200 nm in the aqueous solutions; their structures were confirmed by FTIR and 1H NMR. Cyclodextrin derivatives and their polymers did not affect the secondary structure content of human serum albumin, which might mean a mild effect on the structural and functional properties of the main blood plasma protein. Polymers extract drug molecules from albumin + drug complex by 8–10%, which was demonstrated using ibuprofen and bromophenol blue as model bioactive molecules for site I and site II in protein; thus, the nanoparticles might slightly change the drug's pharmacokinetics. Using the hemolysis test, we found that polymers interact with red blood cells and can be assigned to non-hemolytic and slightly hemolytic groups as biocompatible materials, which are safe for in vivo use. The cyclodextrins and their polymers did not extract proteins from bacterial cell walls and did not demonstrate any antibacterial activity against Gram-positive and Gram-negative strains. Thus, the cyclodextrin-based polymers possess variable properties depending on the substituent in the monomer and linker type; demonstrated biocompatibility, biodegradability, and negligible toxicity that opens up prospects for their application in biomedicine and ecology. [ABSTRACT FROM AUTHOR]

In this investigation, the potential use of native β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) as encapsulating agents for trichloroethylene (TCE) was assessed. Various quantum chemical parameters, including HOMO, LUMO, and HOMO–LUMO gap, were calculated. The docking process was examined by considering different initial configurations. The complexation energies were calculated at the molecular level using DFT/BLYP-D4 and PBEh-3c calculations to gain insight into TCE encapsulation within the β-CD and HP-β-CD cavities. We used the independent gradient model (IGM) and extended charge decomposition analysis (ECDA) approaches to examine non-covalent interactions and charge transfer within TCE@β-CD and TCE@HP-β-CD complexes. The calculated thermodynamic data and complexation energies exhibited negative values for both considered complexes, indicating a favorable complexation process. Weak Van der Waals intermolecular interactions were the main driving forces in stabilizing the formed complex. Additionally, Monte Carlo simulations were conducted for a better understanding of the inclusion process. Our results provide evidence for the use of β-CD and HP-β-CD as suitable macrocyclic hosts for complexing trichloroethylene. [ABSTRACT FROM AUTHOR]

The present study focuses on the synthesis of the natural product 4-methyl-umbelliferone (4-MU, hymecromone), the preparation, characterization, and biological activity evaluation of 4-MU inclusion complexes with β-cyclodextrin (β-CD), as well as their incorporation into pharmaceutical tablets. The inclusion complexes (ICs) were characterized using DLS, SEM, TGA as well as FT-IR, UV-vis, and NMR spectroscopies. The release profile of 4-MU from the β-CD-4-MU ICs was studied in three different pH: 1.2 (aqueous hydrochloric acid), 7.4, and 6.8 (phosphate-buffered solutions), to simulate the stomach, physiological, and intestine pH, respectively. The ICs were incorporated in pharmaceutical tablets which were prepared by direct compression and were characterized for their mechanical properties. The optimal composition of 4-MU as the active pharmaceutical ingredient (API) and excipients was determined using design of experiment (DoE), and the dissolution studies were performed at pH 1.2 at 37 ± 0.5 °C. The sustained release profile of the pharmaceutical tablets showed a delayed burst release effect at 20 min (20% drug release) compared to that of the ICs at the same time interval (70%). The results indicated that the kinetic model describing the release profile of 4-MU from the ICs and tablets is the Higuchi model, while the release mechanism is swelling and diffusion, as was indicated by the Korsmeyer–Peppas kinetic model. The optimization analysis revealed that the optimum composition contains x1 = 150.95 mg of β-CD-4-MU ICs, x2 = 82.65 mg of microcrystalline cellulose, and x3 = 12.40 mg of calcium phosphate. [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.

To obtain a high-performance poly(lactide-co-glycolide) (PLGA)-based composite, a novel functionalized hybrid nanohyoxyapatite (n-HA) was proposed by introducing carboxymethyl-β-cyclodextrin (CMCD) and zoledronic acid (ZA). IR, XRD, TGA, dispersion experiments for hybrid n-HA and universal testing machine, SEM, DSC, POM for the hybrid n-HA/PLGA composite were carried out. The results showed that initial adjusted pH = 11 was more favor for the grafting rate of CMCD, and ZA was preferentially grafted on n-HA surface due to stronger binding ability to Ca2+. The high content of CMCD and ZA of 40%CMCD-10%ZA-n-HA could be well dispersed in organic solvents, which could effectively promote crystallization, so that CMCD-ZA-n-HA displayed the best reinforce effect for PLGA, whose tensile strength and elongation at break were 16.20 and 41.99% higher than PLGA, respectively. In vitro soaking in simulated body fluid (SBF) and cell proliferation results demonstrated that CMCD-ZA-n-HA endowed PLGA with faster degradation, better bone-like apatite deposition and cells adhesion and proliferation ability. The study would provide a new simply method to obtain a functionalized hybrid n-HA, which had a great potential to obtain ideal n-HA/PLGA composite used in the bone materials field. [ABSTRACT FROM AUTHOR]

The chiral separation capability of Chiral-CD-Ph column, containing phenylcarbamate-β-cyclodextrin as the chiral selector in polar organic mode was investigated. A total of twenty-five compounds with different structures and acid–base properties were evaluated, and twenty of them were separated using acetonitrile or methanol as eluent. The effects of various chromatographic parameters, such as the type and proportion of organic modifier, flow rate, and column temperature were analyzed in detail in relation to chromatographic performance. A U-shape retention curve was observed when a mixture of acetonitrile and methanol was used as the eluent, indicating different types of interactions in different solvent mixtures. Van 't Hoff analysis was used for calculation of thermodynamic parameters which revealed that the enantioseparation is mainly enthalpy controlled; however, entropic control was also observed. The enantiomer recognition ability at the atomic level was also investigated through a molecular docking study, which revealed surface binding in polar organic mode instead of inclusion complexation. Our work proves that the phenylcarbamate-β-cyclodextrin-based chiral stationary phase can be effectively used in polar organic mode for the chiral separation of structurally diverse compounds. Furthermore, it is important to note that our study demonstrated that surface binding is responsible for the formation of supramolecular complexes in certain cyclodextrin derivatives. [ABSTRACT FROM AUTHOR]

Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of a parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, caused the apparent permeability coefficient of ranitidine to decrease to 4.62 × 10−5, 4.5 × 10−5, 3.61 × 10−5 and 1.08 × 10−5 in Caco-2 cells, respectively. The same results were obtained from an oral pharmacokinetic study in rats. Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability. [ABSTRACT FROM AUTHOR]

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6′)-Ib. The blaIMP and aac (6′)-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance. [ABSTRACT FROM AUTHOR]

Engineered ultrashort peptides, serving as an alternative to natural antimicrobial peptides, offer benefits of simple and modifiable structures, as well as ease of assembly. Achieving excellent antibacterial performance and favorable biocompatibility through structural optimization remains essential for further applications. In this study, we assembled lipoic acid (LA)–modified tripeptide RWR (LA–RWR) with β–cyclodextrin (β–CD) to form nano–inclusion complexes. The free cationic tripeptide region in the nano–inclusion complex provided high antibacterial activity, while β–CD enhanced its biocompatibility. Compared with peptides (LA–RWR, LA–RWR–phenethylamine) alone, inclusion complexes exhibited lower minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) against typical Gram–negative/Gram–positive bacteria and fungi, along with improved planktonic killing kinetics and antibiofilm efficiency. The antibacterial mechanism of the nano–inclusion complexes was confirmed through depolarization experiments, outer membrane permeability experiments, and confocal laser scanning microscopy observations. Furthermore, biological evaluations indicated that the hemolysis rate of the inclusion complexes decreased to half or even lower at high concentrations, and cell viability was superior to that of the non–included peptides. Preliminary in vivo studies suggested that the inclusion complexes, optimized for antibacterial activity and biosafety, could be used as promising antibacterial agents for potential applications. [ABSTRACT FROM AUTHOR]

Essential oil (EO) is widely used in the pharmaceutical, cosmetic, agriculture, and food industries because of its aromatic, antioxidant, and antibacterial properties. However, the weak interactions caused by small contact area with various substrates pose significant challenges to experimental detection and molecular simulation. In this study, the main components and contents of compound essential oil (CEO) were determined by gas chromatography-mass spectrometry (GC-MS) and gas chromatography (GC), respectively. As a result, 11 components were screened out from CEO and their contents were measured. And synthetic essential oil (SEO) was deployed as a simplified CEO model for subsequent research according to the above result. In addition, a porous cyclodextrin metal-organic framework (CD-MOF) was used to load SEO, and the detailed process of experimental determination and molecular simulation prediction of the content of volatile oil components in CD-MOF was shown. The results of experiments and molecular simulations have consistently proved that CD-MOF had a selective absorption effect on SEO components. Furthermore, the interaction mechanism and release characteristics of these components in CD-MOF were investigated. The results of the release kinetics analysis provided references for the identification of the diffusion type of each component. In conclusion, the strategies established in this article provide ideas for the experimental detection and molecular simulation of multi-component competitive existence in carriers under weak interactions. [ABSTRACT FROM AUTHOR]

This study focuses on the development and characterization of solid dispersions (SDs) of Gefitinib (GEF) to improve its aqueous solubility and therapeutic activity against lung cancer. SDs were prepared by the co-precipitation method with tocopheryl-polyethylene-glycol succinate-1000 (TPGS) (F1), sodium lauryl sulfate (SLS) (F2) and complexation of F1 with hydroxypropyl β-cyclodextrin (HP-β-CD) (F3). Optimal formulations (F1 and F3) were used against A549 cells to determine the apoptosis, expressions of p53 and caspases. F3 has shown the highest solubility (1271.21 µg/mL), followed by F1 (1003.69 µg/mL), F2 (707.81 µg/mL) and GEF pure (303.85 µg/mL) in 0.1N HCl. Dissolution at 1.2 pH significantly enhanced the release from F3 (99.19%), followed by F1 (94.76%), F2 (85.70%) and GEF pure (37.26%) during 120 min. Complexation of GEF–TPGS with HP-β-CD significantly improved drug release with high dissolution efficiency (78.57%) in 24.9 min of mean dissolution time. Differential scanning calorimetry revealed crystalline to amorphous conversion of GEF in SDs, which was confirmed by scanning electron microscopy. Fourier transform infrared and proton nuclear magnetic resonance spectral analysis revealed no interaction between GEF and excipients. The IC50 values were 2.239, 3.135 and 4.471 µM for F3, F1 and GEF pure, respectively, against A549 cells. Increased expressions of p53 (5.9-, 4.6- and 3.04-fold), caspase-3 (5.38-, 3.78- and 3.01-fold) and caspase-9 (5.35-, 3.76- and 2.47-fold) in the case of F3, F1 and GEF pure, respectively, as compared to the untreated A549 cells indicated improved apoptotic potential of the SDs. TPGS SDs and their complexation with HP-β-CD improved the solubility, dissolution and efficacy of GEF against A549 cells. So, they can be a suitable alternative to the conventional GEF formulations against non-small-cell lung cancers. [ABSTRACT FROM AUTHOR]

In the present paper the contributions are directed to obtaining transdermal therapeutic patches provided with a functional cotton textile support (acting as a reservoir) which would result in the controlled release of certain natural active principles (propolis and menthol), with .pharmaceutical action on people and children in order to support the treating and preventing of some irritations, wounds, injuries, scratches as well as certain allergic skin conditions in a natural, efficient and comfortable manner which would avoid the classic administration . In order to prove and characterize the inclusion of the active principles (propolis and menthol) into the cavity of the reactive cyclodextrin product grafted on the surface of the biofunctional textile support the following analytical methods were applied: scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and thermogravimetric analysis (TG-DTG). [ABSTRACT FROM AUTHOR]

Cyclodextrins are present in a variety of oral hygiene compositions. The present work describes the role of cyclodextrins in several toothpastes and mouthwashes that are already available in the market, as well as their prospective use in other applications as investigated in studies in the literature. Moreover, cyclodextrins are under study for the development of materials used in various techniques of dental repair, such as fillings, cements and binders therein. Their role in each of the innovative materials is presented. Finally, the prospect of the use of cyclodextrin-based delivery systems for the oral cavity is introduced, with a focus on new cyclodextrin molecules with dual action as bone-targeting agents and osteogenic drugs, and on new cross-linked cyclodextrin particles with a high drug loading and sustained drug delivery profile for the treatment of diseases that require prolonged action, such as periodontitis. In conclusion, cyclodextrins are herein demonstrated to act as versatile and multi-action ingredients with a broad range of applications in dentistry. [ABSTRACT FROM AUTHOR]

Micro- and nanotechnologies have been intensively studied in recent years as novel platforms for targeting and controlling the delivery of various pharmaceutical substances. Microparticulate drug delivery systems for oral, parenteral, or topical administration are multiple unit formulations, considered as powerful therapeutic tools for the treatment of various diseases, providing sustained drug release, enhanced drug stability, and precise dosing and directing the active substance to specific sites in the organism. The properties of these pharmaceutical formulations are highly dependent on the characteristics of the polymers used as drug carriers for their preparation. Starch and cellulose are among the most preferred biomaterials for biomedical applications due to their biocompatibility, biodegradability, and lack of toxicity. These polysaccharides and their derivatives, like dextrins (maltodextrin, cyclodextrins), ethylcellulose, methylcellulose, hydroxypropyl methylcellulose, carboxy methylcellulose, etc., have been widely used in pharmaceutical technology as excipients for the preparation of solid, semi-solid, and liquid dosage forms. Due to their accessibility and relatively easy particle-forming properties, starch and cellulose are promising materials for designing drug-loaded microparticles for various therapeutic applications. This study aims to summarize some of the basic characteristics of starch and cellulose derivatives related to their potential utilization as microparticulate drug carriers in the pharmaceutical field. [ABSTRACT FROM AUTHOR]

A series of mixed copper (II)—zinc oxide catalysts supported on unmodified and ceria-modified silica supports were synthesized using β-cyclodextrin as a template. The novelty of this work lies in the use of cyclosextrins for the template synthesis of catalyst supports. The obtained samples were analyzed by XRD, SEM-EDX, low-temperature nitrogen physisorption, XPS, and EPR. The magnetic properties of the catalysts were also measured. The thermal decomposition of precursors was analyzed by TGA combined with mass-spectrometric analysis of the evolved gases. The effects of the support pore size, the nature of the active phase and its loading, as well as the sequence of component deposition on the catalyst performance in the CO2 conversion to methanol were studied. The catalysts with cerium added at the gelation stage demonstrated the best performance. The selectivity of these samples reaches values of more than 90% over a fairly ide temperature range, with the productivity reaching 480 g/kg cat·h at 300 °C. [ABSTRACT FROM AUTHOR]

[Display omitted] • Interfacial-assisted supramolecular host–guest polymer show self-tuned interfacial tension. • Host–guest interface acts as the soft template guiding interfacial instability phenomenon. • Soft colloidal aggregates with diverse structure are obtained by self-regulated amphiphilicity. • Light stimuli-altered host–guest assembly/disassembly behavior result in structure diversity. The soft interfacial template-assisted confined self-assembly of block copolymers (BCPs) guiding colloidal aggregates has been extensively investigated by interfacial instability. Whether the macromolecular polymer architectonics possessed stimulus-responsive self-regulated structural controllability more readily implement the morphological diversity of colloidal aggregates. Herein, we in-situ constructed the alginate-modified β-cyclodextrin/azobenzene-functionalized alkyl chains (Alg-β-CD/AzoC12) system by supramolecular host–guest interfacial recognition-engineered strategy, in which possessed photo-stimulated responsive structural reconfigurability by modulating assembly/disassembly behaviors between CD and Azo at oil/water interface. The host–guest droplet interfaces acted as soft templates managing interfacial instability by synergistically integrating supra-amphiphilic host–guest polymers with cosurfactants, further constructing various soft supracolloidal aggregates, including soft nanoaggregates, microspheres with tunable degrees of surface roughness. Additionally, the stimuli-altering structural reconfigurability of supramolecular host–guest polymers was regulated by ultraviolet/visible irradiation, endowing soft aggregates with structural diversity. It's highly anticipated that the supramolecular host–guest interfacial recognition self-assembly establishes great bridge between supramolecular host–guest chemistry and colloid interface science. [ABSTRACT FROM AUTHOR]

For improved wound healing, antimicrobial adhesives are one path forward. However, with the current challenge of bacterial resistance, it is essential to choose the included drug carefully. Octenidine is an obvious choice due to its broad antimicrobial efficacy and no reported bacterial resistance. In its pure form, octenidine complexes efficiently with the platinum catalyst in the silicone composition, inhibiting the targeted hydrosilylation reaction and hindering curing. This obstacle is overcome by screening octenidine with cyclodextrins in homogeneously dispersed glycerol droplets, suppressing Pt inhibition in the silicone phase. Curing efficiency is demonstrated using rheology, which shows that it is possible to incorporate one wt% of octenidine into glycerol–silicone adhesives in the presence of (2-hydroxypropyl)-β-cyclodextrin without affecting the adhesives' mechanical properties. The interaction between octenidine and (2-hydroxypropyl)-β-cyclodextrin through an inclusion complex is confirmed by ROESY spectroscopy. Despite this screening, octenidine is still released efficiently from the glycerol–silicone adhesives upon contact with water, and the resulting antimicrobial action is subsequently demonstrated. This new technology constitutes a simple and efficient method for preparing wound care adhesives that actively inhibit the growth of four bacteria strains and one fungus. [ABSTRACT FROM AUTHOR]

The binding of drugs to nucleic acids, proteins, lipids, amino acids, and other biological receptors is necessary for the transportation of drugs. However, various side effects may also originate if the bound drug molecules are not dissociated from the carrier, especially with the aid of non-toxic agents. The sequestration of small drug molecules bound to biomolecules is thus central to counter issues related to drug overdose and drug detoxification. In this article, we aim to present several methods used for the dissociation of small drug molecules bound to different biological and biomimicking assemblies under in vitro experimental conditions. To this effect, the application of various molecular assemblies, like micelles, mixed micelles, molecular containers, like β-cyclodextrin, cucurbit[7]uril hydrate, etc., has been discussed. Herein, we also try to shed light on the driving forces underlying such sequestration processes through spectroscopic and calorimetric techniques. [ABSTRACT FROM AUTHOR]

Etoricoxib, as a model drug, has a poor solubility and dissolution rate. Cyclodextrin derivatives can be used to solve such a problem. A comparative study was run on three cyclodextrin derivatives, namely β-CD, HP β-CD, and SBE β-CD, to solve the drug problem through the formulation of solid dispersions and their preparation into fast-dissolving tablets. Preparations utilized different (1:1, 1:2, and 1:4) drug:carrier ratios. Nine fast-dissolving tablets (containing 1:4 drug: carrier) were formulated using Prosolv ODT® and/or F-melt® type C as super-disintegrants. Optimized formulation was chosen based on a 32 factorial design. The responses chosen were the outcomes of the in vitro evaluation tests. The optimized formulation that had the highest desirability (0.86) was found to be SD-HP3, which was prepared from etoricoxib: HP β-CD at a 1:4 ratio using equal amounts of Prosolv ODT® and F-melt® type C. An in vivo evaluation of SD-HP3 on a rabbit model revealed its superiority over the marketed product Arcoxia®. SD-HP3 showed a significantly lower Tmax (13.3 min) and a significantly higher Cmax (9122.156 μg/mL), as well as a significantly higher AUC, than Arcoxia®. Thus, the solubility, dissolution, and bioavailability of etoricoxib were significantly enhanced. [ABSTRACT FROM AUTHOR]

Despite the wide pharmacological action of polyphenols, their usefulness is limited due to their low oral bioavailability, which is due to their low solubility and rapid first-pass metabolism. Red vine leaf extract is an herbal medicine containing several polyphenols, with resveratrol and polydatin as the main compounds exhibiting antioxidant and anti-inflammatory properties. In the first stage of the work, using the Design of Experiment (DoE) approach, the red vine leaf extract (50% methanol, temperature 70 °C, and three cycles per 60 min) was obtained, which showed optimal antioxidant and anti-inflammatory properties. In order to circumvent the above-described limitations and use innovative technology, electrospun nanofibers containing the red vine leaf extract, polyvinylpyrrolidone (PVP), and hydroxypropyl-β-cyclodextrin (HPβCD) were first developed. The optimization of the process involved the time of system mixing prior to electrospinning, the mixture flow rate, and the rotation speed of the collector. Dissolution studies of nanofibers showed improved resveratrol release from the nanofibers (over five-fold). Additionally, a PAMPA-GIT assay confirmed significantly better buccal penetration of resveratrol from this nanofiber combination (over ten-fold). The proposed strategy for electrospun nanofibers with the red vine leaf extract is an innovative approach to better use the synergy of the biological action of active compounds present in extracts that are beneficial for the development of nutraceuticals. [ABSTRACT FROM AUTHOR]

Background and Purpose: Despite its contradictory clinical performance, remdesivir (Veklury®) has a pivotal role in COVID‐19 therapy. Possible contributions of the vehicle, sulfobutylether‐β‐cyclodextrin (SBECD) to Veklury® effects have been overlooked. The powder and solution formulations of Veklury® are treated equivalently despite their different vehicle content. Our objective was to study Veklury® effects on initial membrane‐coupled events of SARS‐CoV‐2 infection focusing on the cholesterol depletion‐mediated role of SBECD. Experimental Approach: Using time‐correlated flow cytometry and quantitative three‐dimensional confocal microscopy, we studied early molecular events of SARS‐CoV‐2–host cell membrane interactions. Key Results: Veklury® and different cholesterol‐depleting cyclodextrins (CDs) reduced binding of the spike receptor‐binding domain (RBD) to ACE2 and spike trimer internalization for Wuhan‐Hu‐1, Delta and Omicron variants. Correlations of these effects with cholesterol‐dependent changes in membrane structure and decreased lipid raft‐dependent ACE2–TMPRSS2 interaction establish that SBECD is not simply a vehicle but also an effector along with remdesivir due to its cholesterol‐depleting potential. Veklury® solution inhibited RBD binding more efficiently due to its twice higher SBECD content. The CD‐induced inhibitory effects were more prominent at lower RBD concentrations and in cells with lower endogenous ACE2 expression, indicating that the supportive CD actions can be even more pronounced during in vivo infection when viral load and ACE expression are typically low. Conclusion and Implications: Our findings call for the differentiation of Veklury® formulations in meta‐analyses of clinical trials, potentially revealing neglected benefits of the solution formulation, and also raise the possibility of adjuvant cyclodextrin (CD) therapy, even at higher doses, in COVID‐19. [ABSTRACT FROM AUTHOR]