Search Results (225)

Cetraria islandica (L.) Ach. (CI) is a lichen from the Parmeliaceaea family used in medicine. However, the low solubility of CI secondary metabolites in water limits the application of lichen extract and compounds. It prompted us to study the systems of cyclodextrins (CDs) (β-CD, γ-CD, HP-β-CD, and HP-γ-CD) with the CI acetone or CI methanol extracts prepared using grinding and solvent evaporation methods. The content of fumarprotocetraric acid (FPCA), a key CI metabolite, was quantified using HPLC. CD–extract systems were characterized by X-ray powder diffraction (XRPD) and Fourier-transform infrared (FTIR) spectroscopy. Biological activity was evaluated using cell-free assays: a Folin–Ciocalteu analysis, DPPH test, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitions. Dissolution profiles were also assessed. The best biological and physicochemical results were obtained for systems prepared with HP-β-CD and HP-γ-CD via solvent evaporation, showing higher activity and enhanced FPCA release compared to the pure extracts. To the best of our knowledge, this is the first study to report the preparation and characterization of CD-based systems with CI extracts. The obtained results encourage us to continue our research on CI to improve the physicochemical properties of its active compounds. Full article

Innovative functional materials integrating host–guest complexes in cryogels offer promising applications in topical drug delivery, enhancing drug solubility and stability. In this study, we designed and developed a cryogel-based patch for acne treatment by polymerizing an acrylate-functionalized γ-cyclodextrin (γ-CD) and trimethoprim (TMP) inclusion complex with [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETMA) at low temperatures. A multistep workflow was applied to synthesize the inclusion complex via mortar-assisted kneading, followed by cryogel formulation through radical cryopolymerization. The resulting hybrid system leverages the cationic nature of AETMA to promote adhesion and electrostatic interactions with the skin surface. At the same time, γ-CD serves as a drug reservoir, facilitating sustained release of the drug. The system was characterized by FT-IR, TGA, and SEM analyses. In vitro release studies demonstrated a sustained TMP release profile, best described by the Korsmeyer–Peppas diffusion model. Antibacterial assays confirmed the system’s effectiveness against Staphylococcus aureus, supporting its potential for localized and prolonged acne treatment. Moreover, cytocompatibility tests demonstrated that the formulation is biocompatible, further validating its suitability for topical application. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. Full article

Background: Topical statin therapy holds promise for ocular diseases, such as age-related macular degeneration, but the effective delivery to the posterior segment is limited by poor aqueous solubility, chemical instability, and ocular barriers. Cyclodextrins (CDs) can enhance statin solubility and stability; however, the behavior of CD–statin complexes in aqueous eye drops—particularly their influence on the equilibrium between the inactive lactone (ring closed) and active hydroxyacid forms (ring open)—remains unclear. This study aimed to (i) investigate how 5% and 10% (w/v) concentrations of selected CDs affect the lactone/acid equilibrium of simvastatin and atorvastatin and (ii) define formulation parameters (statin form, CD type and concentration, and pH range) for stable eye drop development. Methods: Simvastatin or atorvastatin was added to buffered solutions (pH 2.0 to pH 9.5) of RMβCD, HPβCD, γ-CD, or SBEβCD at 0%, 5%, and 10% (w/v), incubated at 23 ± 1 °C, and sampled over time for UPLC quantification of lactone and hydroxyacid forms, and rate constants for the forward and reverse reaction were calculated. Phase solubility studies were also conducted to further characterize equilibrium behavior in aqueous CD systems. Results: The lactone form was most stable at a pH of 4.5, while the hydroxyacid form prevailed at a pH ≥ 7. γ-CD and HPβCD accelerated lactone hydrolysis for both statins, whereas RMβCD exerted a stabilizing effect. Increasing the CD concentration from 5% to 10% provided minimal additional stabilization. Conclusions: These findings highlight that the precise control of the pH, an appropriate cyclodextrin choice, and the selection of the statin form are critical to developing chemically stable eye drops. Full article

Linalyl acetate (LA), a key volatile component in essential oils, is extensively utilized in fragrance, food, and cosmetic industries. Nevertheless, its practical applications are constrained by rapid evaporation and physicochemical instability. This study developed novel cyclodextrin–metal–organic frameworks (CD-MOFs) crystallized from β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) with potassium hydroxide, demonstrating superior structural properties for LA encapsulation. Through comparative analysis with native CDs, the synthesized CD-MOFs exhibited highly ordered crystalline architectures and uniform morphological characteristics. The LA encapsulation capacity of the γ-CD-MOF was systematically evaluated under different conditions using a three-level factorial design via RSM. Optimization revealed maximum encapsulation efficiency (25.9%) under ideal conditions—an LA:γ-CD-MOF mass ratio of 3.8:1, 60.9 °C incubation temperature, and 49.3 min processing time—representing a 2.39-fold enhancement over conventional CD encapsulation. Thermal stability analysis demonstrated remarkable improvement, with LA-γ-CD-MOF complexes showing an onset decomposition temperature of 215 °C, 135 °C higher than that of free LA. Compared with LA-γ-CD, LA coated with γ-CD-MOFs still retained 55.7% at 80 °C for 75 min, with the release rate reduced by about 45.3%. These findings establish the potential of γ-CD-MOFs as effective carriers for thermolabile and volatile compounds in functional food and cosmetic industries. Full article

Background/Objectives: Mometasone furoate (MF) is a topical corticosteroid used to reduce allergic and inflammation symptoms. In this study, MF was incorporated into the hydrophobic cavities of γ-cyclodextrin metal-organic frameworks (CD-MOFs) to prepare MF@MOF powders for nasal delivery. Methods: MF@MOF particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry. A transparent biomimetic model of the human nasal cavity was produced by 3D printing and used to evaluate intra-nasal depositions patterns. Results: Drug loading was optimized by incubating MF with a CD-MOF at a ratio of 4% for 1 h at 40 °C, and the cubic morphology and particle size of the nanoparticles were not altered using an incubation method. PXRD and FTIR analyses confirmed the successful loading of MF into the CD-MOF. Using a 3D biomimetic nasal cavity model, a 30° administration angle was found to result in reduced drug accumulation in the nasal vestibule and enhanced deposition in the respiratory and olfactory regions, compared with administration at 45°. Approximately 51% of the drug reached the respiratory zone in the model of the nasal cavity from male subjects, while almost 60% of the drug reached this zone in the model associated with female subjects. Compared with nasal sprays, nasal powder sprays had less deposition in the nasal vestibule and more deposits in the middle and inferior nasal concha. Conclusions: MF@MOF is suitable for intranasal administration. Delivery of MF as a nasal powder shows potential in the treatment of chronic rhinosinusitis. Full article

Background/Objectives: Cyclodextrins (CDs) have garnered increasing attention in pharmaceutical research due to their ability to enhance drug solubility, bioavailability, and therapeutic efficacy. Meanwhile, the gut microbiota, a key regulator of human health, has emerged as an important target in evaluating the safety and broader implications of pharmaceutical excipients. This review aims to synthesize current knowledge regarding the effects of CDs on the composition and function of the gut microbiota. Methods: A literature search following PRISMA guidelines was conducted in PubMed, ScienceDirect, and Google Scholar to identify studies on cyclodextrins and their interactions with gut microbiota. Results: Cyclodextrins, particularly α-, β-, and γ-CDs, demonstrated the capacity to modulate gut microbiota composition, promoting the growth of beneficial bacteria such as Bifidobacterium and Akkermansia. Supplementation with CDs was also associated with an increased production of short-chain fatty acids (SCFAs), which are essential for maintaining intestinal homeostasis and metabolic health. Moreover, CDs exhibited potential in lowering lipid levels and improving postprandial glycemic control without enhancing insulin secretion. Although generally recognized as safe, the toxicological profile of CDs varies depending on their type, dosage, and route of administration. Conclusions: Cyclodextrins hold considerable promise not only as pharmaceutical excipients but also as modulators of gut microbial communities, suggesting a dual therapeutic and prebiotic role. Future studies integrating metagenomic and metabolomic approaches are necessary to further elucidate the molecular mechanisms underlying CD–microbiota interactions and to optimize their application in enhancing drug delivery efficiency and promoting intestinal health. Full article

Polyethyleneimine-based porous composites have been prepared by ring-opening polymerization of 2,2-bishydroxymethylbutanol-tris[3-(1-aziridinyl)propionate] (3AZ), a tri-aziridine compound, in water, in the presence of cyclodextrins (CDs), i.e., α-CD, γ-CD, methyl-β-cyclodextrin (Me-β-CD), monoacetyl-β-cyclodextrin (Ac-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD). The corresponding 3AZ-CD porous polymer composites were successfully obtained in most cases under a wide range of CD concentrations, 5–20 wt%, and reaction temperatures, 20–60 °C. The reaction system in the presence of Ac-β-CD preferentially yielded gels. The polymer composites were composed of connected particles with sizes of the order of 10⁻⁹ m. The particle sizes decreased with an increase in the CD concentration. Young’s moduli of the 3AZ-CD porous polymer composites tended to increase with an increase in bulk density. The 3AZ-CD porous polymer composites with Me-β-CD and HP-β-CD effectively adsorbed phenolphthalein in the solution. The adsorption value increased with increasing the CD content and rose to more than 600 mg/g of porous polymer composite. Full article

Objective: Muscone (MUS), a primary active component of musk, is known for its significant pharmacological properties. However, its clinical application is limited due to poor water solubility and moderate stability. This study aims to address these limitations by encapsulating MUS within biodegradable γ-cyclodextrin metal–organic frameworks (γ-CD-MOFs) using a solvent-free method to enable oral MUS delivery by improving solubility and stability, pending in vivo validation. Methods: MUS was encapsulated into γ-CD-MOFs using a solvent-free method, achieving an optimal loading rate of 10.6 ± 0.7%. Comprehensive characterization was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Biocompatibility was assessed using RAW264.7 cells, and molecular dynamics simulations were conducted to study the interactions between MUS and γ-CD-MOFs. Results: Characterization techniques confirmed the successful encapsulation of MUS into γ-CD-MOFs. Biocompatibility studies revealed no cytotoxicity, indicating that the system is safe for drug delivery. Molecular dynamics simulations showed that MUS preferentially occupies the large spherical cages of γ-CD-MOFs, driven by non-covalent interactions. Solubility tests and in vitro release studies demonstrated that the solubility of MUS was improved after encapsulation within γ-CD-MOFs. Stability assessments indicated that γ-CD-MOFs significantly enhanced the thermal and photostability of MUS, with high residual amounts remaining under various storage conditions. Conclusions: This study demonstrates the potential of γ-CD-MOFs to solidify MUS, enhance its solubility, and improve its storage stability, providing a foundation for its future use in pharmaceutical applications. Full article

The discovery of efficient and stable nanopesticides with improved water solubility and sustained release effects has become particularly important. Pyrimethanil (Pyr) as a low toxicity fungicide of an aniline pyrimidine group is widely used for the prevention and control of gray mold in crops and ornamental plants, however, poor water solubility hinders its further development. Herein, we use a supramolecular self-assembly process to encapsulate a pyrimethanil in a hydroxypropyl-gamma-cyclodextrin (HPγCD) via electrostatic interactions, thereby constructing the inclusion complex nanofibers. The HPγCD as an environmentally friendly carrier material for pesticide delivery is favorable for facilitating the control efficacy, water solubility, and thermostability with Pyr. The diameter of the prepared inclusion nanofiber is 426.6 ± 82.1 nm. Pyr/HPγCD inclusion complex nanofibers could be completely dissolved in water within 3 s. As predicted, the fungicidal activity of Pyr/HPγCD inclusion complex nanofibers is much higher than that of either Pyr, and the EC₅₀ value of Pyr/HPγCD inclusion nanofibers is 0.437 μg/mL, which is about half of that of Pyr (0.840 μg/mL). The inclusion strategy achieved by Pyr and HPγCD is important for improving the safety of nanopesticides. This work provides a versatile insight to promote the development of water-based pesticide dosage forms and reduce pesticide losses in agricultural production. Full article

The tetrahydroisoquinoline skeleton is a pharmacologically significant core structure containing chiral centers, making enantiomeric separation crucial due to the potentially distinct biological effects of each enantiomer. In this study, laudanosine (N-methyl-tetrahydropapaverine) and its three derivatives (6′-bromo-laudanosine, norlaudanosine, and N-propyl-norlaudanosine) were synthesized and used as model compounds to investigate chiral recognition mechanisms. Screening over twenty cyclodextrins (CyDs) as chiral selectors in capillary electrophoresis (CE), we found anionic CyDs to be the most effective, with sulfated-γ-CyD (S-γ-CyD) achieving a maximum R_s of 10.5 for laudanosine. Notably, octakis-(6-deoxy-6-(2-carboxyethyl)-thio)-γ-CyD (sugammadex, SGX), heptakis-(2,3-O-diacetyl-6-O-sulfo)-β-CD (HDAS), heptakis-(2,3-O-dimethyl-6-O-sulfo)-β-CD (HDMS), and octakis-(2,3-O-dimethyl-6-O-sulfo)-γ-CD (ODMS) provided excellent enantioseparation for all four analytes. Following HPLC screening on CyD-based and polysaccharide-based chiral stationary phases, semi-preparative HPLC methods using amylose and cellulose-based columns were optimized to isolate enantiomers. The purity of the isolated enantiomers was evaluated by HPLC, and their configurations were confirmed via circular dichroism spectroscopy. The isolated enantiomers allowed us to explore enantiomer migration order reversals in CE and enantiomer elution order reversal in HPLC. Further ¹H and 2D ROESY NMR experiments provided atomic-level insights into enantioselective complex formation, confirming enantiomer differentiation by SGX and elucidating the inclusion complex structure, where the ring C immersion into the CyD cavity is prevalent. Full article

Heavy-metal contamination of the environment is a serious worldwide issue, as it presents dangerous threats to both human health and aquatic ecosystems. This has led to a paradigm shift toward the development of simple, user-friendly, and economically viable remediation technologies that are essential for addressing heavy-metal soil pollution and for the global preservation of the environment. This review provides a comprehensive overview of environmental remediation strategies using cyclodextrin (CD) and its derivatives. Additionally, this study examines the effectiveness of methylated gamma-cyclodextrin (M-γ-CD) as a modified oligosaccharide for the elimination of toxic elements from impure soil matrices. M-γ-CD has emerged as a potent agent for treating soil impurities with noxious metals. As a modified form of cyclodextrin, M-γ-CD features hydrophobic cavities that are particularly adept at forming inclusion complexes with heavy-metal ions, thereby cumulating the aqueous solubility and efficiency of pollutants in environmental applications and improving soil bioremediation. This paper also reviews the unique structural configuration of M-γ-CD, which significantly enhances the solubility and mobility of cyclodextrins and facilitates the extraction of noxious metal particles such as Ni, Cu, and Pb from soil matrices. Furthermore, M-γ-CD is a promising soil remediation agent due to its capacity to boost contaminant solubility, improve environmental safety, offer cost-effectiveness, ensure adaptability, and minimize impact on soil parameters. Therefore, M-γ-CD is a desirable agent for the elimination of toxic metal impurities from soil. Full article

A good chiral separation usually results in a trial-and-error process; however, through systematic studies, certain principles can be established to correlate structure with chiral selectivity. These principles can then be applied to other chiral separations, reducing the time of developing chiral selective analytical methods. Using the model compounds, the established principles can be applied to a wider range of compounds. In this study, mandelic acid and its substituted derivatives were selected as model compounds to establish transferable rules. The chiral selectivity of 13 compounds was measured on various permethylated cyclodextrin selectors. Comparing the chiral selectivity of permethylated cyclodextrins with different ring sizes (α, β, and γ) provides further insight into the role of inclusion in the chiral selectivity of the cyclodextrin-based stationary phases. Different derivatives of acidic and hydroxyl functions of mandelic acids were tested. Ring- and alkyl-substituted mandelic acid enantiomeric pairs were also tested. By using these compounds, the role of hydrogen donor–acceptor interactions and dipole–dipole interactions and inclusions in chiral recognition processes were investigated. The chiral selectivity values were measured and extrapolated to the same temperature, for the sake of the comparison. Several general tendencies were concluded, which can be used for chiral separation of other enantiomer pairs. Full article

In this short review, recent findings from both theory and experiment regarding the process of hydration of α-, β-, and γ-cyclodextrins are summarized and critically assessed. Key important questions are addressed, including: What factors govern the number of water molecules entrapped in the internal cavity of the host macrocycle? What is the driving force behind this process? What are the “hot spots” for water entrapment inside the host cavity? What is the underlying mechanism of water hydration and dehydration of cyclodextrins? What is the role of the confined water cluster in determining the outcome of the host–guest complexation between cyclodextrins and molecules of inorganic/organic nature? To what extent does water hydration affect the crystalline structure of the cavitand? Full article

Our previous study demonstrated that γ-cyclodextrin (γ-CD)–perilla oil inclusion complexes increase plasma α-linolenic acid and eicosapentaenoic acid levels in healthy rats without adverse effects. The present study examined the effects of perilla oil, γ-CD, and their inclusion complexes on rats fed cholic acid (CA) to mimic the elevated gastrointestinal 12-hydroxylated (12OH) bile acid levels in high-fat diet-fed rats. Rats fed CA (CA group) tended to have higher AST, ALT, plasma total cholesterol (T-CHO), and triglyceride (TG) levels compared to controls fed a standard diet without CA. Rats fed CA and perilla oil (CA+LP group) showed a tendency for lower AST and plasma TG levels than those in the CA group. Rats fed CA and γ-CD (CA+CD group) had significantly higher AST, ALT, plasma T-CHO, and TG levels than the controls, indicating severe liver injury and dyslipidemia. Rats fed CA and the γ-CD–perilla oil inclusion complex (CA+IC group) had significantly lower AST and ALT levels than the CA+CD rats, with a trend towards lower plasma T-CHO and TG levels. Plasma α-linolenic acid and eicosapentaenoic acid levels were significantly higher in the CA+LP and CA+IC groups than in the controls and CA+CD groups. However, the CA+IC group tended to have lower α-linolenic acid levels and significantly lower eicosapentaenoic acid levels than the CA+LP group. This suggests an accelerated conversion of α-linolenic acid to eicosapentaenoic acid in the CA+IC group, which may contribute to the attenuation of liver injury and dyslipidemia. These findings suggest that γ-CD may exacerbate liver injury and dyslipidemia caused by elevated gastrointestinal 12OH bile acid levels, whereas γ-CD–perilla oil inclusion complexes may ameliorate these effects by altering fatty acid metabolism. Furthermore, we recommend evaluating γ-CD safety in both healthy and pathological models and carefully selecting compounds co-ingested with γ-CD. Full article