Search Results (179)

This study investigates the self-assembly and host–guest complexation behaviour of novel resveratrol-based lipophenols (LipoResv)—resveratrol-4′-linoleate (Resv-4′-LA) and resveratrol-4′-docosahexaenoate (Resv-4′-DHA)—with hydroxypropyl-β-cyclodextrins (HP-β-CDs). These amphiphilic molecules display surfactant-like properties, forming micellar aggregates in aqueous media. Fluorescence spectroscopy was used to determine the critical micelle concentration (CMC), revealing that LipoResv exhibit significantly lower CMC values than their free fatty acids, indicating higher hydrophobicity. The formation of inclusion complexes with HP-β-CDs was evaluated based on changes in CMC values and further confirmed by dynamic light scattering (DLS) and molecular modelling analyses. Resv-4′-LA formed 1:1 complexes (Kc = 720 M⁻¹), while Resv-4′-DHA demonstrated a 1:2 stoichiometry with lower affinity constants (K₁ = 17 M⁻¹, K₂ = 0.18 M⁻¹). Environmental parameters (pH, temperature, and ionic strength) significantly modulated CMC and binding constants. Computational docking and molecular dynamics simulations supported the experimental findings by revealing the key structural determinants of the host–guest affinity and micelle stabilization. Ligand efficiency (LE) analysis further aligned with the experimental data, favouring the unmodified fatty acids. These results highlight the versatile encapsulation capacity of HP-β-CDs for bioactive amphiphile molecules and support their potential applications in drug delivery and functional food systems. 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

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity. Full article

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. 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

Despite their broad pharmacological potential, the clinical application of stilbenes derived from Cajanus cajan (L.) Millsp. leaves (CCMLs) is limited by their poor aqueous solubility, resulting in low oral bioavailability. In this study, an inclusion complex of stilbenes extracted from CCMLs and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was successfully developed to improve their solubility and oral bioavailability. The preparation conditions were optimized using the response surface methodology, with an optimum mass ratio of CCML extract (CCMLE) to HP-β-CD of 1.0:8.2 (g/g) and an optimal temperature of 33 °C for 2 h. The maximum inclusion efficiency of stilbenes was 82%, and the physicochemical properties of the inclusion complex were characterized. Both in vitro dissolution studies and in vivo pharmacokinetic evaluation demonstrated that HP-β-CD encapsulation significantly improved the solubility and dissolution rate of stilbenes compared to those of unformulated CCMLE. Notably, the relative bioavailability of cajaninstilbene acid (CSA), longistyle C (LLC) and 4-O-methylpinosylvic acid (MPA) increased to 198%, 177% and 131%, respectively. This work provides a simple and effective strategy to enhance the solubility and bioavailability of naturally derived stilbenes, offering promising potential for the development of other insoluble natural components for both functional food and pharmaceuticals. Full article

Neohesperidin (NH), a bioactive flavanone glycoside, exhibits multifaceted pharmacological properties including antioxidant and anti-inflammatory activities. However, its clinical application is severely constrained by inherent physicochemical limitations such as poor aqueous solubility and instability under physiological conditions. To address these challenges, this study developed a dual-carrier nano-liposomal system through the synergistic integration of phospholipid complexation and hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion technologies. Two formulations—NH-PC (phospholipid complex) and NH-PC-CD (phospholipid/HP-β-CD hybrid)—were fabricated via ultrasonication-assisted ethanol precipitation. Comprehensive characterization using FTIR and PXRD confirmed the amorphous dispersion of NH within lipid bilayers, with complete elimination of crystalline diffraction peaks, indicative of molecular-level interactions between NH’s hydroxyl groups and phospholipid polar moieties. The engineered nanosystems demonstrated remarkable solubility enhancement, achieving 321.77 μg/mL (NH-PC) and 318.75 μg/mL (NH-PC-CD), representing 2.01- and 1.99-fold increases over free NH. Encapsulation efficiencies exceeded 95% for both formulations, with sustained release profiles revealing 60.81% (NH-PC) and 80.78% (NH-PC-CD) cumulative release over 72 h, governed predominantly by non-Fickian diffusion kinetics. In vitro gastrointestinal simulations highlighted superior bioaccessibility for NH-PC-CD (66.35%) compared to NH-PC (58.52%) and free NH (20.85%), attributed to enhanced stability against enzymatic degradation. Storage stability assessments further validated the robustness of HP-β-CD-modified liposomes, with NH-PC-CD maintaining consistent particle size (<3% variation) and encapsulation efficiency (>92%) over 30 days. Antioxidant evaluations demonstrated concentration-dependent DPPH radical scavenging, wherein nanoencapsulation significantly amplified NH’s activity compared to its free form. This study establishes a paradigm for dual-functional nanocarriers, offering a scalable strategy to optimize the delivery of hydrophobic nutraceuticals while addressing critical challenges in bioavailability and physiological stability. Full article

In this study, the influence of various implicit solvent models on the structural and thermodynamic properties of dacarbazine complexes with three cyclodextrins—α-CD, HP-β-CD, and HE-β-CD—was evaluated. The models considered were the polarizable continuum model (PCM), the conductor-like polarizable continuum model (CPCM), the solvation model based on density (SMD), and the Onsager model. Theoretical thermodynamic results were compared with experimental data obtained from conductometric studies. Our findings indicated that all three cyclodextrins form stable 1:1 inclusion complexes with dacarbazine. Among them, the complexes with HE-β-CD were the most thermodynamically stable. While the choice of solvent model had a minor impact on the structural properties of the complexes, it significantly affected thermodynamic parameters such as enthalpy, Gibbs free energy, and solvation free energy. The best agreement with experimental data—particularly for the Gibbs free energy of solvation—was observed when using the SMD model. Full article

Background/Objectives: Rivaroxaban, an oral anticoagulant, shows poor aqueous solubility, posing significant challenges to its bioavailability and therapeutic efficiency. The present study investigates the improvement of rivaroxaban’s solubility through the formation of different inclusion complexes with three cyclodextrin derivatives, such as β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by lyophilization in order to stabilize the complexes and improve dissolution characteristics of rivaroxaban. Methods: The physicochemical properties of the individual compounds and the three lyophilized complexes were analysed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Results: FTIR spectra confirmed the formation of non-covalent interactions between rivaroxaban and the cyclodextrins, suggesting successful encapsulation into cyclodextrin cavity. SEM images revealed a significant morphological transformation from the crystalline structure of pure rivaroxaban and cyclodextrins morphologies to a more porous and amorphous matrix in all lyophilized complexes. XRD patterns indicated a noticeable reduction in drug crystallinity, supporting enhanced potential of the drug solubility. TGA analysis demonstrated improved thermal stability in the inclusion complexes compared to the individual drug and cyclodextrins. Pharmacotechnical evaluation revealed that the obtained formulations (by comparison with physical mixtures formulations) possessed favorable bulk and tapped density values, suitable compressibility index, and good flow properties, making all suitable for direct compression into solid dosage forms. Conclusions: The improved cyclodextrins formulation characteristics, combined with enhanced dissolution profiles of rivaroxaban comparable to commercial Xarelto^® 10 mg, highlight the potential of both cyclodextrin inclusion and lyophilization technique as synergistic strategies for enhancing the solubility and drug release of rivaroxaban. Full article

Objectives: This study was performed to simultaneously improve the solubility, permeability, and pharmacological activity of decoquinate (DQ). Methods: A ternary DQ solid dispersion with hydroxypropyl-β-cyclodextrin (HP-β-CD) and tea saponin (TS) was mechanochemically prepared to enhance the efficacy of DQ. Results: The encapsulation efficiency of the ternary complex reached 93.51%, and the drug loading was 9.48%. The mean particle size was 90.88 ± 0.44 nm. The polydispersity index was 0.244 ± 0.004, and the zeta potential was −38.81 ± 0.75 mV. The sugar ring moiety formed multiple hydrogen bonds with the surface of HP-β-CD, creating favorable conditions for the development of a stable ternary complex through sophisticated molecular interactions that facilitated its assembly. In vivo studies demonstrated that the DQ/HP-β-CD/TS ternary complex drinking water demonstrated superior anticoccidial activity compared to pure DQ and commercial feed formulations against Eimeria tenella. Conclusions: This innovative mechanochemically synthesized ternary complex demonstrates remarkable promise for improving DQ-based formulations, as it simultaneously boosts aqueous solubility, permeability, and therapeutic efficacy. These synergistic enhancements position the compound as a strong candidate for pharmaceutical development. Full article

Enterotoxigenic Escherichia coli (ETEC), a common intestinal pathogen, can colonize the intestines and induce diarrhea in piglets, which brings great economic losses to the swine industry. Antibiotics are recommended to the treatment for diarrhea caused by ETEC in weaned piglets. However, with the emergence and spread of multidrug-resistant ETEC, there is an urgent need to develop alternatives to antibiotics. Due to the unique antibacterial mechanism of targeting bacterial membranes, antimicrobial peptides (AMPs) are promising candidates. In this study, the activity of crude recombinant porcine β-defensin 2 (rPBD2) expressed in Pichia pastoris (P. pastoris) was measured in vitro. Mice infected with ETEC were orally administered 16, 8, and 4 AU crude rPBD2 for 7 consecutive days to evaluate its anti-infective activity in vivo. The results showed that in addition to broad antibacterial activity against Gram-positive and -negative bacteria, crude rPBD2 displayed high tolerance to temperatures ranging from 20 to 60 °C, a broad range of pH, trypsin, pepsin, and physiological concentrations of salts. In an ETEC-induced mouse model, the oral administration of crude rPBD2 decreased diarrhea scores and the intestinal/carcass ratio and alleviated body weight loss. Additionally, crude rPBD2 decreased bacterial loads in stools and the colon (HP group), and the levels of serum pro-inflammatory cytokines IL-6 (HP group) and TNF-α (HP and MP groups), and increased the villus height and the ratio of villus height to crypt depth (VH/CD) in the ileum (HP and MP groups). Our study provides a cost-effective way for PBD2 production and identifies it as a promising candidate to combat ETEC-induced infection. 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

Many antifungal agents, including isoconazole nitrate (ISN), suffer from low aqueous solubility and inconsistent dissolution kinetics, which limit their therapeutic potential. To address these challenges, this study aimed to enhance the solubility and stability of ISN through the development of inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD inclusion complexes were prepared using a spray-drying technique and characterized through phase-solubility studies, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and differential scanning calorimetry (DSC). The inclusion complex significantly improved ISN solubility, increasing from 0.5088 mg/mL to 3.6550 mg/mL. These complexes were incorporated into a thermosensitive, mucoadhesive in situ gel system using Pluronic^® F127 and hydroxypropyl methylcellulose (HPMC) to optimize vaginal drug delivery. The formulations were evaluated for gelation temperature, viscosity, swelling behavior, and pH, confirming their suitability for vaginal application. Antimicrobial studies demonstrated that the ISN/HP-β-CD gels exhibited superior activity against Candida albicans, C. glabrata, and C. krusei compared to ISN alone. In vitro release studies further revealed sustained drug release following Peppas-Sahlin kinetics, supporting enhanced bioavailability and prolonged therapeutic action. This study demonstrates that the ISN/HP-β-CD-loaded in situ gel system offers a promising and effective approach for improving the solubility, stability, and antifungal efficacy of ISN for the treatment of vaginal infections. Full article

This study aimed to improve the solubility of ezetimibe (EZT), which has low aqueous solubility, by preparing complexes using β-cyclodextrin (β-CD) derivatives. Phase solubility studies and Job’s plot confirmed a high apparent stability constant for EZT with β-CD and even higher constants with its derivatives, establishing a 1:1 stoichiometric ratio. The composites were prepared using spray drying over a range of molar ratios, and their physicochemical properties were evaluated using techniques such as scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT-IR). Saturation solubility and in vitro dissolution tests revealed that solubility increased with higher CD molar ratios. EZT/RM-β-CD inclusion complexes (ICs) and EZT/DM-β-CD ICs exhibited a similar solubility, which was greater than that of EZT/HP-β-CD ICs and EZT/SBE-β-CD ICs (where RM, DM, HP, and SEB represent H, CH₃, -CH₂-CHOH-CH₃ and -(CH₂)₄-SO₃Na synthetic derivatives, respectively). Most complexes, except for EZT/SBE-β-CD at 1:2 or higher ratios, showed superior solubility compared with EZT powder and commercial products. Molecular docking simulations confirmed EZT inclusion within the CD, revealing hydrogen bonds and binding energies that aligned with solubility trends. These findings suggest that EZT complexes with β-CD derivatives significantly improve solubility, highlighting their potential for developing more effective oral solid formulations for hyperlipidemia treatment. Full article

Objectives: The effect of 2-hydroxpropyl-β-cyclodextrin (2HPβCD) with or without divalent metal ions (Ca²⁺, Mg²⁺, and Zn²⁺) on the stability of dalbavancin in acetate buffer was investigated. Methods: Dalbavancin recovery from formulations with 2HPβCD and divalent metal ions after four weeks of storage at 5 °C and 55 °C was measured by RP-HPLC and HP-SEC; a longer-term study was carried out over six months at 5 °C, 25 °C, and 40 °C. Binding of 2HPβCD was characterized by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). Results: The stability of the dalbavancin formulations after 4 weeks at 55 °C in 10 mM acetate buffer was significantly improved with 0.6 mM, 5.5 mM, and 55 mM 2HPβCD relative to without 2HPβCD. No further improvement was observed with the addition of any of the divalent cations. Dalbavancin in a 1:10 molar ratio with 2HPβCD was more stable at a concentration of 1 mg/mL than at 20 mg/mL under accelerated conditions at 40 °C for six months. ITC revealed two 2HPβCD binding sites to dalbavancin in 10 mM acetate: one with a 1:1 stoichiometry and thermodynamics consistent with known cyclodextrin–drug interactions, and a second with 0.1:1 stoichiometry, a positive binding enthalpy, and an unusually large entropy of binding. NMR spectroscopy indicates that dalbavancin exhibits aggregation in acetate buffer that is disrupted by 2HPβCD binding. Conclusions: 2HPβCD significantly improves the short- and long-term heat stability of dalbavancin in pH 4.5 acetate buffer at and above molar ratios of 1:1. The strong 1:1 binding of 2HPβCD to dalbavancin demonstrated by ITC confirms that this stability is conferred by the formation of a stable complex. This observation, combined with the NMR results, points to the aliphatic hydrocarbon chain of the glycone moiety as the most likely site of 2HPβCD–dalbavancin interaction. Full article