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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. [ABSTRACT FROM AUTHOR]

A host–guest supramolecular inclusion complex was obtained from the cocrystallization of A1/A2-bromobutoxy-hydroxy difunctionalized pillar[5]arene (PilButBrOH) with adiponitrile (ADN), C47H53.18Br0.82O10·C6H8N2. The adiponitrile guest is stabilized within the electron-rich cavity of the pillar[5]- arene host via multiple C—H...O and C—H...π interactions. Both functional groups on the macrocyclic rim are engaged in supramolecular interactions with an adjacent inclusion complex via hydrogen-bonding (O—H...N or C—H...Br) interactions, resulting in the formation of a supramolecular dimer in the crystal structure. [ABSTRACT FROM AUTHOR]

Summary: Mango is a nutritious fruit but susceptible to the development of black spots on its skin, which can significantly reduce the post‐harvest fruit quality. In response to this challenge, this study focused on preparing and characterising two inclusion complexes (ICs) by combining cinnamon essential oil (CEO) and lemongrass essential oil (LEO) with β‐cyclodextrin (β‐CD), named CEO‐β‐CD and LEO‐β‐CD. Their effectiveness in preserving mango fruit were evaluated. The findings demonstrated the successful encapsulation of essential oils by β‐CD, forming two distinct ICs. Moreover, these ICs notably extended the shelf‐life of mangoes by 40% and 25%, respectively, while reducing black spot occurrence on the fruit skin. Additionally, analysis of physicochemical parameters revealed that the CEO‐β‐CD IC, at a dosage of 2.5 mg per gram of mango, could notably enhance the overall fruit quality. In conclusion, the application of CEO‐β‐CD, at an appropriate concentration, exhibits promising potential as an effective preservative for mangoes. [ABSTRACT FROM AUTHOR]

The formation of inclusion complexes of 2-hydroxypropyl-β-cyclodextrin (HP β-CD) with 2-hydroxychalcone (2HOCH) in solution and solid state was investigated using UV–Visible, fluorescence, Fourier transform-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscope (SEM) techniques. The results obtained confirmed that 2HOCH formed the stable inclusion complex with HP β-CD. Moreover, the spectral data and Benesi–Hildebrand plots results indicated that the stoichiometry of the inclusion complex was 1:1. Theoretically, the structure of the inclusion complexes and the physical parameters such as complexation energy, highest occupied molecular orbital–lowest unoccupied molecular orbital, and energy gap were obtained using the DFT/B3LYP/6-311G method. It was found that the complexation energy for orientation B was lower than that for orientation A as evidenced by the theoretical calculations. Moreover, the carbonyl group of molecules was located outside of the cyclodextrin cavity while the hydroxyl group was located inside the cavity. The antioxidant capacity and antibacterial responses of the inclusion complexes and, for comparison, the parent compounds were also carried out. [ABSTRACT FROM AUTHOR]

We synthesized cinnamic acid derivatives of ethyl cinnamate (EC) and analyzed the resulting products using 1H‐NMR and FTIR spectroscopy. The formation of the confirmed EC and γ‐Cyclodextrin inclusion complex is investigated through UV–vis and fluorescence spectroscopy. Cyclic voltammetry techniques are employed to analyze the formation of the inclusion complex. By using Job's plot, the stoichiometric ratio of the inclusion complex is found to be 1:1, and the binding constant (K) is calculated through the Benesi‐Hildebrand plot. Furthermore, we calculated the thermodynamic parameters (ΔG) using the Gibbs‐Helmholtz free energy equation, indicating that the formation of this inclusion complex is spontaneous. The molecular interaction between EC and the hydrophobic cavity of γ‐CD is characterized using 2D NMR (ROESY), revealing their specific interactions. Research highlights the need for antibacterial studies due to the rise of new infectious diseases. Specifically, the study investigates the antibacterial activity of inclusion complexes compared to the guest molecule alone. [ABSTRACT FROM AUTHOR]

Cyclodextrins (CDs) are macrocycles that are well suited for forming inclusion complexes for surface-enhanced Raman scattering (SERS) detection of analytes due to their low Raman activity, which minimizes background SERS signals and enhances the detection of target molecules without interference. In this paper, we systematically investigated the synthesis of both silver (Ag) and gold (Au) nanoparticles (NPs) using CDs as reducing and capping agents in a basic environment using microwave (MW), ultrasound (US), and room temperature (RT) synthesis. We found that replacing NaOH with K2CO3 as an alkaline environment almost doubles the size (from <10 nm to around 20 nm) of AgNPs in the MW-assisted synthesis. Synthesis using the US produces less stable particles due to the sample evolution after US irradiation. Ag (20 nm) and Au (11 nm) were successfully obtained at room temperature in the presence of CDs and K2CO3. All synthesized particles present SERS activity. CD capping allowed us to detect hydrophobic molecules like naphthalene and melamine. In the case of methylene blue, the CD capping prevents the changes induced in the SERS by a basic pH. We also demonstrate that the newly synthesized NPs can discriminate by SERS the propranolol enantiomers. Moreover, propranolol inclusion in CDs leads to a dramatic change in its SERS spectrum. [ABSTRACT FROM AUTHOR]

Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects. [ABSTRACT FROM AUTHOR]

This study aims to synthesize inclusion complex derived from sorafenib (Sor) and hydroxypropyl-β-cyclodextrin (HPβCD) (denoted as [Sor-HPβCD]). The complex of Sor with HPβCD has been synthesized in a mixed solvent of H2O-DMSO, with a DMSO volume fraction of 80 %. The results of FTIR, DSC, and UV–Vis analysis have demonstrated the success of complex formation: the intensity of some characteristic peaks for the Sor binding decreased after complex formation, indicating that a part of the guest molecule has entered the cavity of the HPβCD molecule. This is further supported by the DSC analysis results, showing the transformation of the complex's crystalline form to an amorphous form. The phase solubility diagram study also indicates that the solubility of Sor significantly increases, approximately 7 times higher than pure Sor, after complex formation. The results of the cell growth inhibition activity test in a water environment show that the complex inhibits the growth of Hep-G2 cells with an IC50 value of 62.4 μg/mL, while pure Sor does not exhibit activity as it is practically insoluble in water. [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]

BACKGROUND: Papaya, a highly nutritious and economically significant fruit, is susceptible to infections caused by phytopathogenic fungi. Cinnamon essential oil, derived from Cinnamomum cassia (CC), shows promise in preserving papaya due to its antifungal properties. However, CC is volatile, sensitive to environmental factors, and carries a strong aroma. γ‐Cyclodextrin (γ‐CD) is known for encapsulating hydrophilic molecules, shielding them from environmental influences, reducing odor, and enabling controlled release due to its unique channel structure. This study aimed to tackle these challenges by preparing and characterizing an inclusion complex of CC with γ‐CD (CC‐γ‐CD), and subsequently evaluating its efficacy in preserving papaya fruits. RESULTS: Analyses, including Fourier‐infrared, powder X‐ray diffraction, thermal gravity analysis, differential scanning calorimeter, and scanning electron microscopy, revealed successful encapsulation of CC components within the γ‐CD cavity. Evaluations of the CC‐γ‐CD complex's impact on papaya fruit shelf life and quality showed notable enhancements. Fruits treated with CC‐γ‐CD inclusion complex at a dose of 10 g kg−1 exhibited a 55% extension in shelf‐life, evidenced by reduced disease severity index compared with untreated fruit in the same storage conditions. Detailed physicochemical and bromatological assessments highlighted significant improvements, particularly in fruit treated with CC‐γ‐CD inclusion complex at a dose of 10 g kg−1. CONCLUSION: The application of CC‐γ‐CD inclusion complex at 10 g kg−1 extended the shelf‐life of papaya fruit, significantly and markedly improved the overall quality. These findings underscore the potential of the CC‐γ‐CD inclusion complex as an effective preservative for papaya, offering a promising solution for its postharvest management and marketability. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/βCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/βCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/βCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1β, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/βCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/βCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1β levels. The effects of the NEO/βCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress. [ABSTRACT FROM AUTHOR]

Essential oils play an important role in the fight against plant pathogens. Clove essential oils are widely used as antifungal, antibacterial, insecticidal, and antioxidant agents. To increase its solubility and reduce its volatility, clove essential oil was encapsulated in β cyclodextrin, using the freeze-drying method at a weight ratio of 16:84. The composition of clove essential oil was evaluated using gas chromatographymass spectrometry (GC-SM). Gas chromatography-mass spectrometry analysis revealed the presence of 11 components, representing 98.7% of the essential oils. The major component was eugenol (79.7%), followed by eugenyl acetate (16.3%). The antifungal activity of clove essential oil and its inclusion complex with β cyclodextrin was tested against an Algerian isolate of Fusarium oxysporum f.sp radicis lycopersici (FORL) and a reference strain, Fusarium oxysporum f.sp lycopersici race 2 (FOL) in liquid medium. The obtained results demonstrated that the antifungal efficiency of clove essential oil against FORL and FOL enhanced after encapsulation in β-cyclodextrin. A significant difference between the inhibition rates obtained with free clove essential oil and those obtained with the inclusion complex (β-cyclodextrin-clove oil) was observed for the concentrations studied. [ABSTRACT FROM AUTHOR]

To improve the efficiency of cyclodextrins as carotenoid carriers, the kinetics and thermodynamics of the inclusion complex formation between modified β-cyclodextrin (βCD-NH2) and β-carotene (βCT) were studied using surface plasmon resonance (SPR) at pH 7.4 and theoretical calculations. The observed dissociation rate of the [βCD-NH2/βCT]° inclusion complex is small (2.59 × 1 0 - 1 s - 1 ), indicating that βCD-NH2 only interacted with the βCT ionone group to form inclusion complex. The βCD-NH2/βCT binding constant is 2.80 × 1 0 4 Lmol - 1 (at 298.15 K), and its temperature dependence indicates that the [βCD-NH2/βCT]° formation is driven by hydrophobic interactions ( Δ H ∘ = 28.83 kJ l - 1 and T Δ S ∘ = 54.21 kJ l - 1 ) caused mainly by the βCT end group desolvation. In contrast, the formation of the [βCD-NH2/βCT]‡ activated complex via association between free molecules and dissociation of [βCD-NH2/βCT]° occurred with the overcoming of an energy barrier ( E a ‡ = 40.77 kJ mol - 1 and E d ‡ = 11.94 kJ l - 1 ) and decrease in entropy ( T Δ S a ‡ = - 11.70 kJ l - 1 and T Δ S d ‡ = - 65.92 kJ l - 1 ). [ABSTRACT FROM AUTHOR]

With the rapid expansion of the scale of nuclear energy, the proper treatment of radioactive waste generated by the nuclear industry has become one of the most important issues for the further development of nuclear energy. Cyclodextrin, as a kind of cyclic oligosaccharide composed of several glucopyranose units, has a good prospect of application in the field of radioactive ions adsorption and separation, because of its special molecular structure of internal hydrophobicity and external hydrophilicity. However, due to the presence of a large number of hydroxyl groups in the cyclodextrin molecules, they are easily soluble in water. Generally, the solidification of cyclodextrins to insoluble solids is always needed before being used as adsorption materials. Depending on the different methods of " solidification", cyclodextrin based adsorbent materials can be divided into three types: loaded cyclodextrin materials, cyclodextrin polymer materials, and cyclodextrin inclusion complex materials. The synthesis and application research advances of the three types of cyclodextrin adsorbent materials in radioactive ion adsorption and separation are summarized, the related adsorption mechanisms are discussed. Besides, the perspectives of the cyclodextrin based adsorbents in the field of radioactive ion adsorption are presented. [ABSTRACT FROM AUTHOR]

A host–guest supramolecular inclusion complex was obtained from the co-crystallization of A1/A2-bromobutoxy-hydroxy difunctionalized pillar[5]arene (PilButBrOH) with adiponitrile (ADN), C47H53.18Br0.82O10·C6H8N2. The adiponitrile guest is stabilized within the electron-rich cavity of the pillar[5]arene host via multiple C—H...O and C—H...π interactions. Both functional groups on the macrocyclic rim are engaged in supramolecular interactions with an adjacent inclusion complex via hydrogen-bonding (O—H...N or C—H...Br) interactions, resulting in the formation of a supramolecular dimer in the crystal structure.

Cyclodextrins (CDs) are cyclic carbohydrate polymers that hold significant promise for drug delivery and industrial applications. Their effectiveness depends on their ability to encapsulate target molecules with strong affinity and specificity, but quantifying affinities in these systems accurately is challenging for a variety of reasons. Computational methods represent an exceptional complement to in vitro assays because they can be employed for existing and hypothetical molecules, providing high resolution structures in addition to a mechanistic, dynamic, kinetic, and thermodynamic characterization. Here, we employ potential of mean force (PMF) calculations obtained from guided metadynamics simulations to characterize the 1:1 inclusion complexes between four different modified βCDs, with different type, number, and location of substitutions, and two sterol molecules (cholesterol and 7-ketocholesterol). Our methods, validated for reproducibility through four independent repeated simulations per system and different post processing techniques, offer new insights into the formation and stability of CD-sterol inclusion complexes. A systematic distinct orientation preference where the sterol tail projects from the CD's larger face and significant impacts of CD substitutions on binding are observed. Notably, sampling only the CD cavity's wide face during simulations yielded comparable binding energies to full-cavity sampling, but in less time and with reduced statistical uncertainty, suggesting a more efficient approach. Bridging computational methods with complex molecular interactions, our research enables predictive CD designs for diverse applications. Moreover, the high reproducibility, sensitivity, and cost-effectiveness of the studied methods pave the way for extensive studies of massive CD-ligand combinations, enabling AI algorithm training and automated molecular design.

Abstract Background Curcumin is a compound that occurs in the rhizomes of the turmeric plant (Curcuma longa) and has shown potential for the treatment of illnesses including certain neurodegenerative diseases. The bioavailability of curcumin is hindered by its extremely poor aqueous solubility. Results This study aimed to apply formulation strategies such as inclusion complex formation with hydroxypropyl-β-cyclodextrin (HPβCD), as well as amorphous solid dispersion (ASD) formation with poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) and hydroxypropyl methylcellulose (HPMC) to increase curcumin’s solubility and thereby its nasal epithelial membrane permeation. The curcumin formulations were evaluated by means of DSC, TGA, FT-IR, XRPD, microscopic imaging, aqueous solubility and membrane permeation across nasal respiratory and olfactory epithelial membranes. The solubility of curcumin was substantially increased by the formulations from 8.4 µg/ml for the curcumin raw material to 79.0 µg/ml for the HPβCD inclusion complex, 256.4 µg/ml for the HPMC ASD and 314.9 µg/ml for the PVP VA64 ASD. The HPMC ASD only slightly changed the membrane permeation of curcumin, while the PVP VA64 ASD decreased the membrane permeation of curcumin. The HPβCD inclusion complex enhanced the nasal epithelial membrane permeation of curcumin statistically significantly across the olfactory epithelial tissue and extensively across the respiratory epithelial tissue. Conclusion Complexation of curcumin with HPβCD enhanced the solubility of curcumin and thereby also increased its permeation across excised nasal respiratory and olfactory epithelial tissue. This indicated high potential of the curcumin-HPβCD complex for nose-to-brain delivery of curcumin for treatment of neurodegenerative diseases by means of intranasal administration. Graphical abstract

Rutin has a variety of pharmacological activities, in order to solve the application defects caused by its poor water solubility. In this paper, rutin/hydroxypropyl-β-cyclodextrin (HPCD) inclusion complexes were prepared by solvent evaporation method and analysed for structure, solubility, antioxidant activity and stability. The analysis of the inclusion complex showed that HPCD could effectively encapsulate rutin in a molar ratio of 1:1, and its encapsulation efficiency and drug loading rate were 89.33% and 26.67%, respectively. The solubility of the inclusion complex in water was 51 times higher than that of rutin. After complexation, the crystal diffraction peaks of rutin disappeared and the temperature of the maximum weight loss increased from 266 ℃ to 318 ℃ and solid inclusion complex forms showed an irregular sheet-like structures indicating a successful complexation of rutin by HPCD. The IC50 of the inclusion complex for scavenging DPPH radicals and ABTS cationic radicals was significantly lower than that of rutin (P

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.

Abstract 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.

There is an urgent need to develop safer and more effective modalities for the treatment of numerous pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Over the past decades, cyclodextrins (CDs) have gathered great attention as potential drug carriers due to their ability to enhance their bioactivities and properties. Likewise, selenium (Se) and tellurium (Te) have been extensively studied during the last decades due to their possible therapeutical applications. Although there is limited research on the relationship between Se and Te and CDs, herein, we highlight different representative examples of the advances related to this topic as well as give our view on the future directions of this emerging area of research. This review encompasses three different aspects of this relationship: (1) modification of the structure of the different CDs; (2) formation of host–guest interaction complexes of naïve CDs with Se and Te derivatives in order to overcome specific limitations of the latter; and (3) the use of CDs as catalysts to achieve novel Se and Te compounds. [ABSTRACT FROM AUTHOR]

Background: Curcumin is a compound that occurs in the rhizomes of the turmeric plant (Curcuma longa) and has shown potential for the treatment of illnesses including certain neurodegenerative diseases. The bioavailability of curcumin is hindered by its extremely poor aqueous solubility. Results: This study aimed to apply formulation strategies such as inclusion complex formation with hydroxypropyl-β-cyclodextrin (HPβCD), as well as amorphous solid dispersion (ASD) formation with poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) and hydroxypropyl methylcellulose (HPMC) to increase curcumin's solubility and thereby its nasal epithelial membrane permeation. The curcumin formulations were evaluated by means of DSC, TGA, FT-IR, XRPD, microscopic imaging, aqueous solubility and membrane permeation across nasal respiratory and olfactory epithelial membranes. The solubility of curcumin was substantially increased by the formulations from 8.4 µg/ml for the curcumin raw material to 79.0 µg/ml for the HPβCD inclusion complex, 256.4 µg/ml for the HPMC ASD and 314.9 µg/ml for the PVP VA64 ASD. The HPMC ASD only slightly changed the membrane permeation of curcumin, while the PVP VA64 ASD decreased the membrane permeation of curcumin. The HPβCD inclusion complex enhanced the nasal epithelial membrane permeation of curcumin statistically significantly across the olfactory epithelial tissue and extensively across the respiratory epithelial tissue. Conclusion: Complexation of curcumin with HPβCD enhanced the solubility of curcumin and thereby also increased its permeation across excised nasal respiratory and olfactory epithelial tissue. This indicated high potential of the curcumin-HPβCD complex for nose-to-brain delivery of curcumin for treatment of neurodegenerative diseases by means of intranasal administration. [ABSTRACT FROM AUTHOR]

The article presents the results of studies on obtaining water-soluble complexes of biologically active hydrazides and hydrazones derived from derivatives of o- and p-hydroxybenzoic acids. Hydrazones are widely used in medicine as antitubercular antibacterial and anti-inflammatory drugs, antiseptics, preservatives and other bioactive substrates. Most of them are characterized by low solubility in water, which limits their further study for biological activity. The paper shows that hydrazides of o- and p-hydroxybenzoic acids and their hydrazone derivatives can form various inclusion complexes with natural macromolecular biopolymers. The new hydrazone products considered in this article are able to dissolve in water and also form stable aqueous dispersions. Obtaining water-soluble complexes of these compounds can lead to an increase in their bioavailability, which, accordingly, will allow to significantly reduce their therapeutic concentration. Complexes between biopolymer and substrate molecules have been shown to be quite stable. In this case, the host complexing molecule will contribute to the protection of the substrate molecule from interaction with various highly reactive molecules, reducing the rate of oxidation, hydrolysis and/or degradation, as well as the probability of steric rearrangements and racemization. The new inclusion complexes of hydrazides and hydrazones of o- and p-hydroxybenzoic acids described in this work have been characterized by IR and NMR-1H spectroscopy, differential scanning thermogravimetry and scanning electron microscope. [ABSTRACT FROM AUTHOR]

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

Cyclodextrins are macrocyclic rings composed of glucose residues. Due to their remarkable structural properties, they can form host–guest inclusion complexes, which is why they are frequently used in the pharmaceutical, cosmetic, and food industries, as well as in environmental and analytical chemistry. This review presents the reports from 2011 to 2023 on the quantitative structure– activity/property relationship (QSAR/QSPR) approach, which is primarily employed to predict the thermodynamic stability of inclusion complexes. This article extensively discusses the significant developments related to the size of available experimental data, the available sets of descriptors, and the machine learning (ML) algorithms used, such as support vector machines, random forests, artificial neural networks, and gradient boosting. As QSAR/QPR analysis only requires molecular structures of guests and experimental values of stability constants, this approach may be particularly useful for predicting these values for complexes with randomly substituted cyclodextrins, as well as for estimating their dependence on pH. This work proposes solutions on how to effectively use this knowledge, which is especially important for researchers who will deal with this topic in the future. This review also presents other applications of ML in relation to CD complexes, including the prediction of physicochemical properties of CD complexes, the development of analytical methods based on complexation with CDs, and the optimisation of experimental conditions for the preparation of the complexes. [ABSTRACT FROM AUTHOR]

The aim of the research was to investigate and compare the interaction between flavanones (flavanone, 4-chloro-flavanone) with potential anticancer activity and selected cyclodextrins. Measurements were made using calorimetric (ITC, DSC) and spectrophotometric (UV-Vis spectroscopy, FT-IR, 1H NMR) methods. The increase in the solubility in aqueous medium caused by the complexation process was determined by the Higuchi-Connors method. As a result of the study, the stoichiometry and thermodynamics of the complexation reaction were determined. The formation of stable inclusion complexes at a 1:1 M ratio between flavanone and 4-chloroflavanone and the cyclodextrins selected for research was also confirmed. [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]

The inclusion complex of diphenylamine (DPA) in 2-hydroxypropyl β-cyclodextrin (HP-β-CD) was synthesized by a co-precipitation method. The structure and molecular properties of the newly synthesized inclusion complex (DPA: HP-β-CD) were investigated along with a β-cyclodextrin (β-CD) inclusion complex (DPA: β-CD) using various analytical and theoretical methods. Phase solubility, absorption, fluorescence, Fourier transform-Infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and scanning electron microscope (SEM) techniques were used to investigate the structural properties of the DPA before and after being encapsulated by the CDs (β-CD and HP-β-CD). Furthermore, the antioxidant and antibacterial activities were evaluated for DPA and the inclusion complexes (DPA: β-CD and DPA: HP-β-CD). The structure of the inclusion complexes was proposed based on the experimental results and their structural optimization was done using Becke's three parameter density functional theory using Lee-Yang-Parr's 3-21 G method in the gas phase. Then the various theoretical molecular properties, such as frontier molecular orbitals (FMO), molecular electrostatic potential map (MEP), Mulliken atomic charges, natural bond orbitals (NBO), electron localization function (ELF), localized orbital locator (LOL), quantum theory of atoms in a molecule (QTAIM) and noncovalent interactions—reduced density gradient (NCI-RDG) were studied for DPA and its inclusion complexes using the Gaussian 09 W software and Multiwfn 3.8 tool. [ABSTRACT FROM AUTHOR]

Rutin has a variety of pharmacological activities, in order to solve the application defects caused by its poor water solubility. In this paper, rutin/hydroxypropyl-β-cyclodextrin (HPCD) inclusion complexes were prepared by solvent evaporation method and analysed for structure, solubility, antioxidant activity and stability. The analysis of the inclusion complex showed that HPCD could effectively encapsulate rutin in a molar ratio of 1:1, and its encapsulation efficiency and drug loading rate were 89.33% and 26.67%, respectively. The solubility of the inclusion complex in water was 51 times higher than that of rutin. After complexation, the crystal diffraction peaks of rutin disappeared and the temperature of the maximum weight loss increased from 266 ²C to 318 ²C and solid inclusion complex forms showed an irregular sheet-like structures indicating a successful complexation of rutin by HPCD. The IC50 of the inclusion complex for scavenging DPPH radicals and ABTS cationic radicals was significantly lower than that of rutin (P<0.05), and its ferric ion reduction capacity was 1.2 times that of rutin. The stability study also showed a higher retention rate of rutin in the inclusion complex after exposure to natural light for 6 days (31.80%, 66.70%) or heat treatment at 50 ²C for 15 days (66.91%, 87.38%). The complexation of rutin by HPCD significantly improved its solubility, antioxidant activity and stability, which could be used in different environments to exert its health functions. [ABSTRACT FROM AUTHOR]

Sulfonated β-cyclodextrin (CD1) combined with nanocurcumin or nanoclay was used to prepare multifunctional polyurethane (PU) coatings having antimicrobial capabilities. The combination resulted in formation of an inclusion complex which is confirmed by Raman studies and Job's plot analysis. The co-precipitation method is employed to achieve two inclusion complexes by combining CD1 with Cloisite 30B (C30B) and nanocurcumin (NC) separately. The resultant nanocomposite coating samples exhibit < 100 °C deviation at 50% weight loss from PU in heat resistance, as well as a 78% enhancement in toughness and 2.3–3 cm of zone of inhibition which is comparable to amoxicillin in its performance in resistance to bacterial growth. The advantage of absorbing such inclusion complexes into polymer coatings is the creation of multifunctionalities such as hydrophobicity, flame retardance, thermally stable and low intumescent coatings. [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]

In this study, we report a novel per-6-substituted β-cyclodextrin (4) featuring seven phosphoramidate moieties as an innovative host for inclusion. This structurally well-defined host has remarkable water solubility and was isolated in pure form. Analytical techniques such as NMR and ITC were used to probe the molecular interactions with different drug molecules. Our investigations revealed that host 4 can form 2:1 inclusion complexes with various drugs. Further studies showed that the inclusions of drugs by β-CD host (4) are mostly enthalpy driven, highlighting the potential roles played by the phosphoramidate functionalities of the host. Comparatively, a per-O2, O3-acetylated analog (6) of compound 4 was also obtained, which also shows unusual water solubility but diminished inclusion capability. [ABSTRACT FROM AUTHOR]

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]

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL. [ABSTRACT FROM AUTHOR]

α-CD:N2O "host-guest" type complexes were formed by a simple solid–gas reaction (N2O sorption into α-CD) under different gas pressures and temperatures. The new N2O inclusion method applied in the present study was compared with the already known technique based on the crystallization of clathrates from a water solution of α-CD saturated with N2O. A maximum storage capacity of 4.5 wt.% N2O was achieved when charging the cyclodextrin from a gas phase. The amount of included gas decreases to 1.3 wt.% when the complex is stored in air at 1 atm and room temperature, analogous to that achieved by the crystallization of α-CD:N2O. Furthermore, it was shown that the external coordination of N2O to either the upper or lower rim of α-CD without hydration water displacement is the preferred mode of binding, due to hydrogen bonds with neighboring -OH groups from the host macrocycle and three of the hydration water molecules nearby. The capacity of α-CD to store N2O and the thermal stability of the α-CD:N2O complex demonstrated promising applications of these types of complexes in food and beverages. [ABSTRACT FROM AUTHOR]

Silver-cobalt nanoparticles were synthesised using a chemical reduction technique. Olanzapine-cyclodextrin inclusion complex containing Ag and Ag/Co nanoparticles was examined using UV-Visible, fluorescence, computational method, FT-IR, differential scanning colorimeter, X-RD, FE-SEM, and TEM methods. A blue-shifted absorption maximum was seen in the presence of the OP/CD inclusion complex with silver and silver/cobalt nanoparticles. Multiple emission was noted in the α-CD and β-CD. TEM images conformed the formation of nanorods in Ag/OP/CD and Ag/Co/OP/CD. The pure isolated OP drug or Ag/OP/CD and Ag/Co/OP/CD do not exhibit any antibacterial activity. [ABSTRACT FROM AUTHOR]

As a powerful imidazole antifungal drug, ketoconazole's low solubility (0.017 mg/mL), together with its odor and irritation, limited its clinical applications. The inclusion complex of ketoconazole with randomly methylated β-cyclodextrin was prepared by using an aqueous solution method after cyclodextrin selection through phase solubility studies, complexation methods, and condition selection through single factor and orthogonal strategies. The complex was confirmed by FTIR (Fourier-transform infrared spectroscopy), DSC (differential scanning calorimetry), TGA (thermogravimetric analysis), SEM (scanning electron microscope images), and NMR (Nuclear magnetic resonance) studies. Through complexation, the water solubility of ketoconazole in the complex was increased 17,000 times compared with that of ketoconazole alone, which is the best result so far for the ketoconazole water solubility study. In in vitro pharmacokinetic studies, ketoconazole in the complex can be 100% released in 75 min, and in in vivo pharmacokinetic studies in dogs, through the complexation, the Cmax was increased from 7.56 μg/mL to 13.58 µg/mL, and the AUC0~72 was increased from 22.69 μgh/mL to 50.19 μgh/mL, indicating that this ketoconazole complex can be used as a more efficient potential new anti-fungal drug. [ABSTRACT FROM AUTHOR]

The scope of this review gives an insight into the inclusion complex of essential oil (EO) using cyclodextrins (CDs), including mechanism, preparation and characterization. It also mentioned that this process was influenced by the size of the inner cavity of CDs and the chemical profile of EOs. The scope has looked forward to derivative CDs, which are further modifications of native CDs to achieve more solubility and efficiency by adding hydroxyl, sulfobutylether, and methyl groups, and by using an esterification process. Subsequently, the cyclodextrin metal organic frameworks, which correspond to native CDs connected via a metal cation, were anticipated as a biocompatible porous material demonstrating a more sustained release of EOs. Indeed, supramolecular cyclodextrins obtained through the covalent binding between cyclodextrins and cross-linked reagents led to higher water solubility, stability, and sustained release. It then moves on to combining CD with biopolymer by grafting or dual encapsulation, which was studied to modulate the profile of EO release. It then moves on experimental designs used to optimize the encapsulation efficiency to reduce the amount of CD and EO added, minimize energy and time, and optimize the medium efficacy. [ABSTRACT FROM AUTHOR]

Cyclodextrins (CDs) are well-known agents in drug delivery systems as they can improve the physical properties of drugs with their distinctive features. Oxymetholone (OXYM) is a derivative of testosterone, a steroid drug that is widely used in the treatment of various diseases. In the current research, the inclusion complexes of OXYM with carboxymethyl-β-cyclodextrin (CM-β-CD/OXYM) and β-cyclodextrin (β-CD/OXYM) have been successfully prepared to improve stability, solubility, and biopharmaceutical profile of OXYM. The characterization of the prepared inclusion complexes was carried out using FT-IR, XRD, TGA, DLS, BET, and UV–Vis techniques. In addition, the morphology of the synthesized inclusion complexes was evaluated in terms of their FE-SEM images. The encapsulation efficiency (EE%), phase solubility, and in vitro drug release of the products were also evaluated using a simple spectrophotometric method. In addition, the kinetic study of in vitro drug release was conducted using the appropriate mathematical equations. In view of the findings of this study, a higher solubility was observed for CM-β-CD/OXYM compared to β-CD/OXYM, nearly three times higher. Furthermore, the in vitro drug release study indicated that β-CD/OXYM offers higher release rates, and the kinetic study demonstrated that both carriers follow a non-Fickian mechanism.

[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]

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest–host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole–cyclodextrin), and that the therapeutic effect was not influenced by the entrapment. [ABSTRACT FROM AUTHOR]

The ability of β-CD to form inclusion complexes with ibuprofen (IBU) and at the same time to make a two-phase system with citric acid was explored in the present study for achieving improved solubility and dissolution rate of IBU. Mechanical milling as well as mechanical milling combined with thermal annealing of the powder mixtures were applied as synthetic methods. Solubility and dissolution kinetics of the complexes were studied in compliance with European Pharmacopoeia (ICH Q4B). β-CD and citric acid (CA) molecules were shown to interact by both ball milling (BM), thermal annealing, as well as BM with subsequent annealing. Complexes were also formed by milling the three compounds (β-CD, CA and IBU) simultaneously, as well as by a consecutive first including IBU into β-CD and then binding the formed β-CD/IBU inclusion complex with CA. As a result, ternary β-CD/IBU/CA complex formed by initial incorporation of ibuprofen into β-CD, followed by successive formation of a two-phase mixture with CA, exhibited notably improved dissolution kinetics compared to the pure ibuprofen and slightly better compared to the binary β-CD/IBU system. Although the addition of CA to β-CD/IBU does not significantly increase the solubility rate of IBU, it must be considered that the amount of β-CD is significantly less in the ternary complex compared to the binary β-CD/IBU. [ABSTRACT FROM AUTHOR]

Context: Hydroxypropyl-β-cyclodextrin (HPβCD) is one of the derivatized cyclodextrins most widely used as an excipient in the pharmaceutical industry, for its capacity to improve certain drugs properties. Different configurations of HPβCD are possible depending on the number and location of the 2-hydroxypropyl groups substituted on the glucose rings. Rifampicin has become the most commonly clinically used antibiotic against tuberculosis in recent years, despite its low solubility and variable bioavailability. Different techniques and materials have been proposed to enhance the properties of rifampicin: cyclodextrin complexation is one of them. The van der Waals term was the main contribution to the interaction energy, which then decisively conditioned the complex configurations. The size of rifampicin did not allow the whole molecule to fit into the host. Moreover, interaction energy was much greater when the guest was located near each rim of HPβCD, where rifampicin was partially included in the cavity and formed inclusion complexes. The piperazine tail of rifampicin was included inside the host in minimum energy structures and the guest was situated near the primary rim of HPβCD in most cases, although the complex configurations depended on the degree of substitution. Methods: A molecular mechanics simulation based on the GROMOS 53A6 force field was applied in this work to study the inclusion complexes formed by twelve configurations of HPβCD, with different degrees of substitution and rifampicin in water solution. We determined the penetration potential, the complex structures with minimum energies, the possibility of forming inclusion complexes other than those of minimum energies and potential energy surfaces. [ABSTRACT FROM AUTHOR]

Our modern study is going to inspect new inclusion phenomena between the 1-butyl-2,3-dimethylimidazolium tetrafluoroborate [Bdmim]BF4 ionic liquid (IL) and the host α-Cyclodextrin (α-CD) by a 1:1 ratio and newly formed inclusion complex was further explored by the 1H-NMR, FT-IR, UV–vis spectroscopy, PXRD, DSC, and SEM analysis. Molecular docking was also performed to investigate the encapsulation of the inclusion complex in which orientation and it have been seen that the IL [Bdmim]BF4 enters into the α-CD cavity with a 1:1 ratio was further established with the help of Job's plot. Furthermore, the antibacterial activity of [Bdmim]BF4 IL and its inclusion complex was verified against some Gram-positive and Gram-negative bacterial strains. [ABSTRACT FROM AUTHOR]