Search Results (375)

Xylazine (XYL), an FDA-approved veterinary tranquilizer, is being abused both as an opioid adulterant in a street-drug known as “Tranq-dope” and as a date rape drug. Given its now nearly ubiquitous use with fentanyl and fentanyl derivatives across the globe, XYL has become a primary target for researchers seeking to develop portable and cost-effective sensors for its detection. Electrochemical sensors based on the oxidation of XYL, while useful, have limitations due to certain interferents and inherent electrode fouling that render the approach less reliable, especially in certain sample matrices. In this work, modified electrode platforms incorporating layers of multi-walled carbon nanotubes for sensitivity along with semi-permeable polyurethane (PU) layers and host–guest chemistry using β-cyclodextrin for selectivity are deployed for XYL detection using complementary adsorptive cathodic stripping analysis. The modified electrode sensors are optimized to minimize high potentials and maintain fouling resistant capabilities and investigated to better understand the function of the PU layer. The use of adsorptive cathodic stripping differential pulse voltammetry indirectly indicates the presence and concentration of XYL within complex sample media (beverages and synthetic urine). When used in this manner, the modified electrodes exhibited an overall average sensitivity of ~35 (±9) nA/μM toward XYL with a limit of quantification of <10 ppm, while also offering adaptability for the analysis of XYL in different types of samples. By expanding the capability of these XYL sensors, this study represents another facet of tool development for use by medical professionals, first-responders, forensic investigators, and drug-users to limit exposure and help stem the dangerous and illegal use of XYL. Full article

This study aimed to analyze whether the enhancement of the biopharmaceutical efficiency of mebendazole, a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Objectives: Two advanced oral formulations were developed, polyvinyl alcohol-derived nanoparticles (NP) and β-cyclodextrin citrate inclusion complexes (Comp), both employing mebendazole as an anthelmintic agent. The primary objective of this work is to treat trichinellosis, an infection with severe chronic effects. Methods: The physicochemical characteristics as well as the in vivo performance of the NP and Comp formulations were assessed. The in vivo studies involved the bioavailability analysis, comparing drug absorption between the pure drug and the novel formulations, as well as the in vitro anthelmintic activity and in vivo therapeutic efficacy against Trichinella spiralis encysted muscle larvae. The in vivo efficacy was evaluated during the parenteral stage of T. spiralis infection in male and female mice from two genetically distinct lines differing in mebendazole pharmacokinetic parameters and susceptibility to the parasite. Results: The formulations exhibited smaller particle sizes and improved dissolution properties compared to pure MBZ. The pharmacokinetics studies indicate that NP and Comp significantly improved MBZ bioavailability. Both NP and Comp significantly increased mebendazole’s anthelmintic activity against the encysted parasites, which would be attributed to the improved MBZ absorption. The formulations overcome the drug’s poor solubility and low bioavailability limitations, resulting in a higher plasma concentration of the active drug, even at low doses. Conclusions: These findings suggest that the newly designed mebendazole formulations are suitable for treating T. spiralis chronic infection and highlight a potential improvement in the pharmacological treatment of trichinellosis. Full article

The escalating crisis of multidrug resistance, together with the persistence of antibiotic residues in clinical and environmental matrices, demands integrated strategies that couple sensitive detection, efficient decontamination, and controlled delivery. However, current techniques for quantifying avibactam (AVI)—a broad-spectrum β-lactamase inhibitor—such as HPLC-UV lack the sensitivity and specificity required for both therapeutic drug monitoring and environmental surveillance. Encapsulation of AVI within cyclodextrins (CDs) may simultaneously enhance its stability, bioavailability, and detectability, while the high binding affinities of CDs position them as molecular traps capable of scavenging residual AVI. In this study, the inclusion complexation of AVI with various CDs was examined through molecular dynamics (MD) simulations, experimental isothermal titration calorimetry (ITC), and non-covalent interaction (NCI) analysis. Stable 1:1 inclusion complexes were observed between AVI and β-cyclodextrin (β-CD), 2,6-dimethyl-β-cyclodextrin (DM-β-CD), and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), with standard Gibbs free energies of binding (ΔG°) of –3.64, –3.24, and –3.11 kcal/mol, respectively. In contrast, γ-cyclodextrin (γ-CD) exhibited significantly weaker binding (ΔG° = –2.25 kcal/mol). DFT-based NCI analysis revealed that cooperative interaction topology and cavity complementarity, rather than the sheer number of localized contacts, govern complex stability. Combined computational and experimental data establish β-CD derivatives as effective supramolecular hosts for AVI, despite an entropic penalty in the DM-β-CD/AVI complex. These CD–AVI affinities support the development of improved analytical methodologies and pharmaceutical formulations, and they also open avenues for decontamination strategies based on molecular trapping of AVI. Full article

Oxidative stress is one of the key elements in lung-related complications such as cystic fibrosis, acute lung injury, pulmonary hypertension, bronchopulmonary dysplasia, chronic airway diseases, lung cancer, COVID-19, and many others. Antioxidant and anti-inflammatory therapy can be considered as supportive alternatives in their management. However, most naturally derived antioxidants face issues with poor aqueous solubility and stability, which hinder their clinical utility. Remarkably, local pulmonary delivery circumvents the severe limitations of oral delivery, including hepatic first-pass metabolism and organ toxicity, and enables a higher drug payload in the lungs. Here, in this review, we present cyclodextrin as a potential drug carrier for pulmonary administration, exploring the possibilities of its surface modification, complexation with other drug transporters, and loading of cannabidiols, siRNA, and antibodies as future trends. However, the lack of a robust physiological model for assessing the efficacy of lung-oriented drug targeting is a significant concern in its path to clinical and commercial success. Full article

In this study, supramolecular inclusion complexes composed of komecosanol (Ko), a lipophilic compound derived from rice bran, and α-cyclodextrin (αCD) were prepared using a solvent-free three-dimensional (3D) ball milling method. Their physicochemical properties were examined using various techniques. Powder X-ray diffraction analysis of the ground mixture at a Ko/αCD ratio of 1/8 revealed the disappearance of diffraction peaks characteristic of Ko and the emergence of new peaks, indicating the formation of a distinct crystalline phase. Moreover, differential scanning calorimetry analysis showed the disappearance of the endothermic peaks corresponding to Ko, indicating molecular-level interactions with αCD. Near-infrared spectroscopy results suggested the formation of hydrogen bonds between the C–H groups of Ko and the O–H groups of αCD. Solid-state ¹³C CP/MAS NMR and T₁ relaxation time measurements indicated the formation of a pseudopolyrotaxane structure, while scanning electron microscopy images confirmed distinct morphological changes consistent with complex formation. These findings demonstrate that 3D ball milling facilitates the formation of Ko/αCD inclusion complexes with a supramolecular architecture, providing a novel approach to improve the formulation and bioavailability of poorly water-soluble lipophilic compounds. Full article

This study presents the results of a study of the synthesis and properties of 2-hydroxy-β-cyclodextrin functionalized by silver nanoparticles and its loading with a bioactive component. As a reducing agent and stabilizer, 2-Hydroxy-β-cyclodextrin (2gβCD) was used in the production of silver nanoparticles. The use of 2gβCD-AgNPs in loading molecules of the plant alkaloid lupinine (Lup) and its acetyl derivative (Lac) with bactericidal properties were studied. The formation of Lup-2gβCD-AgNPs and Lac-2gβCD-AgNPs was confirmed by UV spectroscopy and X-ray diffraction spectroscopy (XRD). Transmission electron microscopy (TEM) showed that the synthesized AgNPs had a spherical shape. ¹H-, ¹³C-NMR nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy (FT-IR) confirmed the reduction and encapsulation of AgNPs by 2gβCD. Thermographic data show that the obtained Lup and its derivative inclusion complexes reduced energy barriers. This makes them promising components for thermosensitive functional materials. Encapsulated complexes of Lup and its acetate inclusion with silver nanoparticles demonstrated significantly (p < 0.05) higher antibacterial, cytotoxic, and moderately pronounced analgesic activity. Full article

Perilla oil, a plant-derived lipid rich in α-linolenic acid (ALA), has demonstrated enhanced bioavailability when administered as an inclusion complex with γ-cyclodextrin (γ-CD). Crucially, it remains unclear whether this enhancement requires complex formation or can be achieved simply by co-ingestion. To address this, we compared the effects of a γ-CD–perilla oil inclusion complex to the effects of a physical mixture of the two on the plasma fatty acid profiles of rats fed these preparations for four weeks. Both treatment groups showed significant alterations in plasma fatty acid composition compared to the control group. Notably, our results indicated no significant differences between the inclusion complex and physical mixture groups. These findings suggest that γ-CD facilitates the intestinal absorption of perilla oil through co-ingestion, irrespective of its complexation status. This highlights the potential of γ-CD as a practical and effective delivery aid for improving the bioavailability of ALA-rich oils. Further studies are warranted to elucidate the underlying mechanisms and their applicability to human nutrition. Full article

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

The increasing demand for sustainable and safer alternatives in the cosmetic industry has driven the search for multifunctional natural ingredients. Essential oils (EOs), known for their antimicrobial and antioxidant activities, are promising candidates with which to replace synthetic preservatives and antioxidants. This study aimed to evaluate the preservative and antioxidant potential of Lippia origanoides Kunth essential oil, in pure and encapsulated in β-cyclodextrin form, for cosmetic applications. The EO exhibited strong antioxidant activity, with low IC₅₀ values in DPPH and ABTS assays, and demonstrated antimicrobial efficacy, particularly against Escherichia coli and Staphylococcus aureus. Six cosmetic cream formulations were developed and tested for physicochemical and microbiological stability. Formulations with pure EO maintained high antioxidant performance and remained free of bacterial and fungal contamination over time, outperforming the commercial preservatives. In contrast, formulations with encapsulated EO exhibited delayed antioxidant and antimicrobial activity, indicating gradual release. Overall, Lippia origanoides EO proved to be an effective natural alternative to synthetic preservatives and antioxidants. This approach aligns with the current trend of eco-friendly formulations, offering a sustainable solution by incorporating plant-derived bioactives into cosmetic products. Full article

Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming inclusion complexes with various guest molecules, enhancing solubility, stability, and bioavailability. This review outlines the structural features of native CDs and their chemically modified derivatives, emphasizing the influence of functionalization on host–guest interactions. Synthetic approaches for CD derivatization are summarized, with attention to recent developments in stimuli-responsive systems and targeted drug delivery. Analytical techniques commonly employed for characterizing CD complexes, such as spectroscopy, thermal analysis, and molecular modeling, are briefly reviewed. Applications in pharmaceutical formulations are discussed, including inclusion complexes, CD-based conjugates, and nanocarriers designed for solubility enhancement, controlled release, and site-specific delivery. Special consideration is given to emerging multifunctional platforms with biomedical relevance. The regulatory status of CDs is addressed, with reference to FDA- and EMA-approved formulations. Safety profiles and toxicological considerations associated with chemically modified CDs, particularly for parenteral use, are highlighted. This review presents an integrative perspective on the design, characterization, and application of CD-based systems, with a focus on translational potential and current challenges in pharmaceutical development. Full article

Cyclodextrins (CDs) have been widely employed as natural host molecules to form inclusion complexes with bioactive molecules such as antioxidants. Their particular spatial configuration, in the form of truncated cones formed through α(1–4) ether linkages of glucopyranose units, makes them very appropriate for the formation of host–guest complexes, modifying their physicochemical properties and their location in multiphasic systems. Here, we investigated the effects of 2-hydroxypropyl-β-cyclodextrin (HPCD) on the efficiency of a series of gallic acid derivatives (propyl (PG), butyl (BG), octyl (OG), and lauryl (LG) gallates) in inhibiting the oxidation of soybean oil-in-water emulsions. For this purpose, we investigated the effects of HPCD on both the kinetics of lipid oxidation and the distribution of antioxidants in the same intact emulsions. The results show that in an aqueous solution, the antioxidants form 1:1 inclusion complexes with HPCD, with inclusion constants ranging from 383 M⁻¹ (PG) to 1946 M⁻¹ (OG). The results also show that the addition of HPCD to emulsions containing antioxidants does not lead to significant changes in their antioxidant effectiveness, with their efficiency being similar to that when no HPCD molecules are present. The results are interpreted in terms of the blocking effect exerted by the Tween 20 molecules, which act as effective guest competitors capable of removing the antioxidants from the HPCD cavity. The Tween 20 surfactant molecules need to be employed to stabilize the emulsions kinetically. This blocking effect, as a primary consequence, indicates that the interfacial concentration of the antioxidants, which is the region where the inhibition reaction takes place, remains constant; thus, their efficiency is not altered. Full article

Resveratrol is one of the most extensively studied natural products due to its pleiotropic health benefits. However, its low water solubility and limited stability hinder its application in the nutraceutical, cosmetic, and pharmaceutical sectors. In this work, we investigated the ability of a cationic mono-choline-β-cyclodextrin derivative to complex trans-resveratrol. The complex was prepared using a phase solubility method without using organic solvents and was found to be stable after freeze-drying. The complex was characterized by a phase solubility study, NMR spectroscopy, and molecular modeling simulations, which revealed a 1:1 stoichiometry, a stability constant of 2051 M⁻¹ (K_C), and structural details. Complexation improved resveratrol’s solubility and dissolution rate, reduced its photoinduced trans-to-cis isomerization, and preserved its radical scavenging activity. The wound-healing activity of the complex was demonstrated via in vitro experiments on human keratinocyte cells. Full article

Background/Objectives: In order to enhance the biological activity, novel complexes of N-(2-bromo-phenyl)-2-hydroxy-benzamide derivatives and β-cyclodextrin were obtained. Methods: The inclusion complexes were characterized using spectral and thermal analyses. The antimicrobial activity was determined using the disk diffusion agar method, and completed with the minimum inhibitory concentration (MIC) values obtained by the broth microdilution method. The in vitro anti-inflammatory activity was evaluated using the protease inhibition assay. Results: The computed supramolecular architectures of the inclusion complexes showed that the most stable molecular arrangements correspond to the models in which the N-(2-bromo-phenyl)-2-hydroxy-benzamide derivatives are partially included in the cyclodextrin cavity. The antimicrobial screening showed that the compounds were active against Gram-positive bacteria (MIC = 2.5–5.0 mg/mL). Also, the evaluation of the proteinase inhibitory activity showed that the IC₅₀ values of the title compounds (0.04–0.07 mg/mL) were much lower than that of the acetylsalicylic acid (0.4051 ± 0.0026 mg/mL) used as positive control, proving their superior efficiency in inhibiting trypsin activity. Conclusions: The complexation proved to be beneficial for both antimicrobial and anti-inflammatory effects. Full article

Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4⁺, CD4⁺CD25⁺, and CD4⁺CD25⁺FoxP3⁺, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((o-Fph)PPhβCD), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (o-Fph)PPhβCD significantly restored CD4⁺ and CD4⁺CD25⁺ T-cell levels and induced a sustained reduction in regulatory CD4⁺CD25⁺FoxP3⁺ cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (o-Fph)PPhβCD exerted a more prolonged response, which was particularly evident by day 14. Structural confirmation of the inclusion complex was achieved through IR and NMR spectroscopy. These findings highlight (o-Fph)PPhβCD as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation. Full article

Satureja montana L. (winter savory, family Lamiaceae) is an aromatic herb that is widespread throughout the Mediterranean region. In a prior study, the optimization of the green hydroxypropyl-β-cyclodextrin (HP-β-CD)-glycerol-assisted extraction procedure of S. montana was performed. As a result, four extracts abundant in total phenols (OPT-TP), total phenolic acids including rosmarinic acid (OPT-TPA-RA), total flavonoids (OPT-TF), and luteolin derivatives (OPT-LG) showing anti-elastase and anti-hyaluronidase properties, were prepared. Subsequently, we further explored the phytochemical, dermatological, and cosmeceutical potentials of these extracts, evaluating their antioxidant, anti-inflammatory, anti-tyrosinase, and anti-ultraviolet (UV) absorption activities. Furthermore, the biocompatibility of the extracts and their wound-healing properties were assessed using HaCaT cells. The results indicate that the extracts exhibited excellent antioxidant and cosmeceutical activities, which surpassed the activities of the employed standards in several assays (DPPH antiradical activity, β-carotene-linoleic acid, anti-lipoxygenase, anti-heat-induced ovalbumin coagulation, and UV absorbance assays). Furthermore, the extracts preserved more than 80% of the HaCaT cell viability at concentrations up to 62.5 µL extract/mL and also enhanced wound healing in the in vitro scratch wound-healing model. For example, the application of OPT-TP and OPT-TF led to 48.6% ± 3.3% and 48.6% ± 5.4% wound closure, respectively, after 48 h, compared to 34.8% ± 2.3% in the control group. The extracts exhibited excellent bioactivities, making them promising candidates for the development of cosmeceutical products, while their high biocompatibility indicates that they are suitable for direct application in cosmetics without prior solvent removal. Full article