Search Results (295)

(1) Background: Carvedilol is a poorly water-soluble drug, which limits its therapeutic performance. Deep eutectic solvents (DES) and cyclodextrins (CD) are emerging solubilizing agents that can improve drug bioavailability. (2) Methods: Twenty-one DES were prepared using choline chloride and polyols or sugars (xylitol, sorbitol, glucose, and fructose) at different molar ratios with water. α and β cyclodextrins (CD) were added (0.5–2 mM) using two incorporation strategies: (Method 1) addition to the aqueous phase before DES formation; (Method 2) direct addition to the preformed DES. (3) Results: Carvedilol solubility markedly increased with DES–CD combinations. In Method 1, xylitol-based DES provided up to a 16-fold enhancement, especially with β-CD at low concentrations, while glucose and sorbitol systems showed modest effects. Fructose-based mixtures improved mainly at a 2:1:35 ratio without CDs. In Method 2, α-CD with xylitol or sorbitol yielded the highest increases (up to 38.9-fold). (4) Conclusions: The solubilization efficiency depends on DES composition, CD type, and concentration. α-CD combined with xylitol-based DES showed the best results, highlighting this approach as a promising strategy to enhance carvedilol solubility for pharmaceutical applications. Full article

Surimi-based products are widely popular in the market owing to their unique texture and nutritional properties; however, traditional processing methods often result in reduced lipid content, despite lipids playing a crucial role in health. This study evaluated the effects of adding glycosylated fish gelatin emulsifying gel (prepared by glycosylating fish gelatin (FG) with D(+)-glucose (Glu) or β-cyclodextrin (β-CD) for 2 h) at 5%, 10%, and 15% (w/w) to hairtail surimi on its gel properties. The results indicated that both emulsified gels significantly enhanced gel strength, texture, and visual whiteness of hairtail surimi gel, with FG-βCD showing more pronounced improvements. FG-βCD also substantially reduced exudation and improved moisture distribution, resulting in a 69.81% decrease in juice loss. Furthermore, the addition of gelatin emulsifying gels shifted protein secondary structures toward more ordered forms, increasing α-helix and β-sheet content while reducing disordered components. Chemical interaction analysis revealed that hydrophobic interactions and nonspecific binding contributed to the reinforcement of gel formation. In conclusion, these findings highlighted that glycosylated emulsifying gels, as functional exogenous additives for surimi, offer a viable strategy for developing lipid-enriched, high-quality surimi products that meet emerging nutritional demands. Full article

Despite the growing interest in orally disintegrating films (ODFs), developing soy protein isolate (SPI)-based ODFs with both rapid disintegration and high functional stability remains a challenge. This study developed a novel SPI-based ODF incorporated with a cinnamaldehyde/β-cyclodextrin (CA/β-CD) inclusion complex at varying concentrations (5–20%, w/w) to address this gap. The control ODF exhibited poor structural order, a slow disintegration rate, and weak antioxidant activity. The incorporation of an appropriate amount of CA/β-CD inclusion complex (10–15%) significantly improved the comprehensive properties of the ODFs. The inclusion complex facilitated the formation of an orderly, continuous network structure, leading to a substantial enhancement in tensile strength (TS), elongation at break (EAB), disintegration rate, thermal stability, and sustained antioxidant activity. An excessive inclusion complex concentration (20%) induced agglomeration, compromising the structural integrity and functionality of the ODF. FTIR and secondary structure analyses revealed that the enhanced hydrogen bonding between the CA/β-CD inclusion complex and the SPI matrix promoted the transformation of disordered protein structures into ordered conformations (β-sheets and α-helices). This structural ordering is the core mechanism driving the improved macroscopic physicochemical and functional properties of the ODFs. This study confirms that CA/β-CD inclusion complexes can enhance the performance of SPI-based ODFs and provide a highly promising delivery system for hydrophobic bioactive substances. Full article

Objective: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong–Vinegar cyperus rotundus based on Quality by Design (QbD) principles. Methods: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS). Single-factor experiments were conducted to preselect the inclusion speed based on ligustilide and α-cyperone content as evaluation criteria. Subsequently, using the inclusion rates of ligustilide and α-cyperone as evaluation criteria, a factorial design was employed to investigate the inclusion temperature, inclusion time, and the volume ratio of β-cyclodextrin solution to essential oil, thereby optimizing the inclusion process parameters. Finally, the inclusion process parameters were validated, and the inclusion rates were determined. The obtained inclusion complexes were characterized by microscopic analysis, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Furthermore, phase dissolution studies and molecular docking were employed for confirmation. Results: The optimal process parameters were determined as follows: encapsulation speed of 300 rpm, β-cyclodextrin solution excess of 6, encapsulation time of 2.5~3 h, and encapsulation temperature of 30~35 °C. The encapsulation rates for ligustilide and α-cyperone in the resulting inclusion complex were 63.15~64.74% and 71.33~76.89%, respectively. Structural characterization confirmed the formation of the inclusion complex. Conclusions: This inclusion process is reliable and provides a reference for preparing β-cyclodextrin inclusion complexes of volatile oils in formulations containing the Chuanxiong–Vinegar cyperus rotundus drug pair. Full article

Cyclodextrins (CDs) are cyclic oligosaccharides composed of α(1 → 4) linked glucose units, which are widely used as solubilizers and stabilizers in the food, pharmaceutical and cosmetic industries. Among the CDs, γ-CD has attracted much attention due to its larger hydrophobic cavity and higher solubility. However, the industrial production of γ-CD is limited by lack of suitable enzymes and production process shortcomings. In this study, various strategies of improving heterologous enzyme production and optimization of the starch conversion process were applied to increase the production of γ-CD. A γ-cyclodextrin glucanotransferase with good product specificity from Bacillus sp. FJAT-44876 (BFγ-CGTase) and a liquefying β-CGTase from Bacillus sp. 1011 (Bsβ-CGTase) were successfully secreted by Pichia pastoris. After codon optimization and using the one-factor-at-a-time (OFAT) principle to improve the fermentation, the yield of recombinant BFγ-CGTase was increased 13.3 times to 463 U/L. Next a process was established involving Bsβ-CGTase-assisted starch liquefaction and simultaneous pullulanase debranching and BFγ-CGTase production of γ-CD. The yield of γ-CD increased by 17.67% via optimizing the amounts of BFγ-CGTase and BtPul used for the reaction. Overall, combination of the various improvements provided a new process for efficient preparation of γ-CD. Full article

Essential oils from species of the genus Varronia (Boraginaceae) are recognized for their chemical diversity and biological potential; however, phytochemical information on Varronia crenata Ruiz & Pav. remains scarce, despite its wide distribution in the Andean region. The aim of this study was to provide the first chemical and enantioselective characterization of the essential oil obtained from the leaves of V. crenata growing in Ecuador. Qualitative and quantitative analyses were carried out by GC–MS and GC–FID, respectively, using two columns with stationary phases of contrasting polarity. Compounds were identified by matching linear retention indices and mass spectra to literature references and quantified by external calibration using relative response factors (RRFs) calculated for each compound based on its combustion enthalpy. The most abundant constituents (≥3.0% on average between the two columns) of the essential oil of V. crenata, both in the nonpolar and polar stationary phases, were germacrene D (18.4%), (E)-β-caryophyllene (13.3%), α-copaene (10.4%), tricyclene (9.3%), δ-cadinene (8.9%), and α-pinene (8.3%). The volatile fraction was dominated by sesquiterpenes (60.2%) and monoterpenes (22.1%), while other chemical families were present in minor proportions. The enantioselective analysis was performed on two different columns, coated with stationary phases based on β-cyclodextrins: 2,3-diacetyl-6-tert-butyl-dimethylsilyl-β-cyclodextrin and 2,3-diethyl-6-tert-butyl-dimethylsilyl-β-cyclodextrin. Nine chiral compounds were analyzed; among them, (1R,5R)-(+)-α-pinene, (1R,5R)-(+)-sabinene, and (S)-(+)-β-phellandrene were detected as enantiomerically pure, while the other metabolites presented scalemic mixtures. Overall, the high content of bioactive sesquiterpenes and the observed stereochemical complexity highlight the potential pharmaceutical and agricultural relevance of V. crenata essential oil, while also providing novel chemotaxonomic information for the genus. Full article

Background/Objectives: Reducing the dietary intake of sugar and salt is considered a key strategy for preventing the onset and progression of lifestyle-related diseases. However, these dietary interventions often compromise the taste of foods, which can reduce patient satisfaction. To address this challenge, we focused on novel food-derived particles (NFPs; patent number P7383867) consisting of lipid, α-cyclodextrin, and xanthan gum formulated as an emulsion with excellent retention and diffusion properties. Methods: Here, we investigated the effects of NFPs on the taste responses of mice. Results: In two-bottle preference tests (n = 4–6), NFPs enhanced preferences for sweet and salty stimuli in behavioral tests (one-way ANOVA, p < 0.05) and increased the responses of the chorda tympani nerve (n = 6–8) to sweet and salty stimuli (two-way ANOVA, main treatment effect p < 0.05), but had no effect on the responses to sour, bitter, or umami stimuli. Conclusion: These findings suggest that NFPs may enhance peripheral taste responses to sweet and salty flavors, thereby helping maintain the palatability of foods with reduced sugar or salt content. Such modulation may have broad applications in improving the acceptability of therapeutic or restricted diets and supporting both disease management and prevention, including lifestyle-related diseases, kidney disease, and other conditions requiring dietary restriction and may offer translational relevance for human dietary interventions. Full article

Spray freeze-drying (SFD) is a novel technique for formulating dry powders, particularly for pulmonary drug delivery via dry powder inhalers (DPIs). Despite their low density and excellent aerodynamic properties, such powders are affected by high cohesiveness due to their surface properties. Sugars such as mannitol (MAN), trehalose, raffinose, and sucrose are commonly used in SFD. MAN is widely employed due to its high MAN—ice eutectic temperature—at which MAN and water (ice) form a stable eutectic mixture—and its crystallinity. However, crystallinity can impact the microparticles’ (MPs) cohesiveness, since MAN exhibits distinct polymorphs (α, β, δ) with peculiar properties. This study provides valuable insights for the development of DPI formulations by ensuring precise control over MAN polymorphism, ultimately enhancing formulation stability and performance. We introduced, for the first time, an intermediate freezing (IF) step within the SFD process to modulate MAN polymorphism, demonstrating its synergy with optimised storage temperature conditions. Furthermore, polyvinylpyrrolidone, 2-hydroxypropyl beta cyclodextrin, dextran, and polysorbate 80 were employed as polymorphism-controlling agents for MAN, contributing to the development of stable formulations with reduced particle cohesion and improved storage stability at room temperature. For the first time, this study shows that MAN polymorphism in SFD can be controlled to drive dry powder inhaler performance. Full article

This study reports measurements of density, viscosity, and ternary mutual diffusion coefficients (D₁₁, D₁₂, D₂₁, D₂₂) for aqueous solutions containing two antibiotics—sulfamethoxazole (SMX) or trimethoprim (TMP) (component 1)—in the presence of various cyclodextrins (α–CD, β–CD, and γ–CD) (component 2) at 298.15 K. The relative viscosity data were analyzed by fitting to a second-order Jones-Dole equation via a least-squares regression to obtain the viscosity B coefficients. Apparent molar volumes (V_ϕ) were derived from the measured densities (ρ) for SMX and TMP in aqueous media. Furthermore, partial molar volumes of transfer at infinite dilution, ΔV_ϕ⁰, were evaluated to elucidate solute–solvent interactions within the ternary systems investigated. Nonzero ΔV_ϕ⁰ values, positive viscosity B coefficients, and negative cross-diffusion coefficients (D₁₂ and D₂₁), evidencing significant coupled diffusion, collectively indicate strong interactions between the antibiotics and cyclodextrins, consistent with host–guest complex formation. Full article

Lipid debris generated after ischemic stroke overwhelms myeloid cells, leading to foam cell-like dysfunction and chronic neuroinflammation. 2-hydroxypropyl-β-cyclodextrin (HPβCD), a cholesterol-mobilizing agent, has been shown to improve recovery and reduce chronic inflammation after stroke by enhancing lipid processing and cholesterol efflux in infarcts. To identify plasma biomarkers of HPβCD activity and gain mechanistic insight into lipid pathway modulation, aged (21-month-old) male mice underwent the distal middle cerebral artery occlusion + hypoxia (DH) model of stroke and received 2 g/kg HPβCD twice daily beginning 1 d after stroke. Plasma metabolomic and lipidomic profiling was performed 4 d after stroke using untargeted (Global Discovery) and targeted (Complex Lipid, Oxysterols, and Lipid Mediators of Inflammation) panels. Acute neuroprotection was assessed by magnetic resonance imaging (MRI) quantification of infarct, ventricle, and hippocampus volumes 2 d after stroke and by plasma neurofilament light (NfL) levels 4 d after stroke. HPβCD treatment did not provide acute neuroprotection; however, HPβCD did induce distinct plasma metabolomic and lipidomic signatures, including decreases in sphingolipids, cholesterol, long-chain fatty acids, 4β-hydroxycholesterol, 7-dehydrocholesterol, and 8-dehydrocholesterol and increases in 27-hydroxycholesterol and 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA), consistent with enhanced cholesterol efflux and metabolism. Pro-inflammatory oxylipins were also suppressed by HPβCD treatment. These results support the role of HPβCD in promoting lipid debris clearance and suppressing inflammatory lipid pathways after stroke and, together with prior studies demonstrating improved long-term recovery, highlight HPβCD as a biomarker-supported therapeutic candidate for stroke recovery. Full article

Background: Despite extensive phytochemical research on white tea varieties, flavonoid profiling in Baihao Yinzhen remains scarce. The development of green and efficient extraction methods is essential to facilitate its potential application in cosmetic formulations. Methods: A deep eutectic solvent-based ultrasound-assisted extraction (DES-UAE) was developed for Baihao Yinzhen flavonoids. After screening of 14 DESs and optimizing the conditions via single-factor and response surface methodology, the extracts were analyzed by UPLC-MS. Anti-inflammatory activity was assessed in LPS-induced RAW264.7 cells by measuring TNF-α and IL-6 levels, with molecular docking simulating flavonoid–cytokine interactions; Results: Among 14 tested deep eutectic solvents, hydroxypropyl-β-cyclodextrin/lactic acid (HP-β-CD/La) was identified as the most effective solvent for flavonoid extraction. Under optimized conditions (HBD/HBA mass ratio 3:1, temperature 60 °C, water content 40%, solid–liquid ratio 1:19, extraction time 62 min), the maximum flavonoid yield reached 108.72 mg RE/g DW. The DES extract (2.5 μg/mL) significantly suppressed TNF-α and IL-6 secretion in LPS-stimulated RAW264.7 cells compared to the water extract. UPLC-MS identified five major flavonoid glycosides, and molecular docking revealed their strong binding affinities with TNF-α and IL-6 proteins. Conclusions: DES-UAE provides an efficient green method for flavonoid extraction. The extract demonstrates significant anti-inflammatory activity, supporting its potential as a natural cosmetic ingredient. This study aimed to develop an efficient and green DES-UAE method for the extraction of flavonoids from Baihao Yinzhen, in order to evaluate the antioxidant and anti-inflammatory activities of the extract and to explore the potential interaction mechanisms of key flavonoids with inflammatory targets via molecular docking. Full article

Hydroxytyrosol (HXT), a phenolic compound from olive, shows great potential as a neuroprotective agent and a translational target for claim-ready nutrition and food products. Human studies increasingly report benefits for vascular function, inflammatory tone, and early cognitive/psychomotor outcomes, consistent with engagement of redox and signalling pathways (Keap1–Nrf2–ARE, PI3K/Akt–ERK, and AMPK–SIRT1–PGC-1α). HXT is rapidly absorbed and likely reaches the brain, acting on endothelial and microglial targets. On the neurovascular axis, it reduces oxidative stress, preserves nitric-oxide bioavailability, lower inflammatory markers, and favourable intrinsic connectivity. For product development, bitterness from oleuropein-rich inputs can be mitigated by hydrolysis, followed by structure-guided delivery to balance sensory quality with exposure. Viable formats include cyclodextrin inclusion, microencapsulation, and (micro)emulsions in lipid matrices, plus stability engineering for aqueous systems (acidification, chelation, low-oxygen handling, or barrier packaging). Matrix effects are consequential; some proteins and fibers may decrease HXT bioaccessibility, whereas lipid phases and microstructured carriers often enhance it. Clinically, recommended doses are ~7–15 mg/day chronically and ~30–60 mg acutely. As conclusions of this review, future work should prioritize harmonized pharmacokinetics–pharmacodynamics readouts, cognition anchored to a compact neurovascular/blood–brain barrier biomarker core, and head-to-head comparisons of manufacturable delivery formats. Full article

Lepechinia mutica, an endemic species of the Ecuadorian Andes, was studied to identify the seasonal variation in volatile organic compounds emitted from leaves and flowers in winter and summer using solid-phase microextraction–gas chromatography–mass spectrometry (SPME-GC-MS). A total of 101 and 100 volatile compounds were identified in flowers and leaves, respectively. The main compounds in flowers were β-phellandrene (7.81–17.74%), dictamnol (3.57–31.89%) and 9-epi-(E)-caryophyllene (3.93–14.37%), while in the leaves, they were dictamnol (9.85–34.64%), (Z)-β-ocimene (1.24–29.24%) and δ-3-carene (1.14–11.51%). This is the first report of enantiomeric separation in L. mutica using a capillary column with 2,3-diethyldecyl-6-tert-butyl-dimethylsilyl-β-cyclodextrin, revealing three enantiomerically pure compounds as (S)-(-)-β-pinene, (1S,3R)-(+)-δ-3-carene and (S)-(+)-linalool, while (+) (-) α-pinene, (+) (-) δ-cadinene and (+) (-) α-muurolene were found as racemic mixtures. Principal component analysis confirmed distinct chemical profiles between plant parts and seasons. This result has important implications for the future highlighting its potential as a source of seasonally variables components with applications in fragrance and phytotherapy. Full article

The search for bioactive compounds against chronic diseases such as cancer and diabetes includes curcuminoids as promising scaffolds. Here, we report the synthesis of a family of curcuminoid analogue compounds with an extended unsaturated central chain, as follows: difluoroboron complex 1, the enolised curcuminoid 2, and its homoleptic copper complex 3, in moderate to good yields (68–90%). Additionally, their β-cyclodextrin (BCD) association complexes, 4 and 5, were prepared through a mechanochemical method and characterised by spectroscopic techniques. Complete ¹H and ¹³C NMR assignments and NOESY correlations revealed unique solvent effects on the conformational disposition of compound 2, while the copper complex 3 displayed the highest extinction coefficient (1.20 × 10⁵ M⁻¹·cm⁻¹). Furthermore, the authentication of the polymorph of 1 and the new crystal structures of 2 and 3, determined by single-crystal X-ray analysis, were highlighted. Although the copper complex 3 initially exhibited the lowest a-glucosidase inhibitory activity (IC₅₀ > 100 µM), it showed a significant increase (IC₅₀ = 36.27 µM) upon association with BCD, reaching values comparable to the free ligand (IC₅₀ = 45.63 µM). Compounds 1–5 were non-toxic to healthy cells (COS-7), but compound 5 stands out as a promising candidate against this metabolic condition. Full article

Carmustine (BCNU) is a powerful alkylating agent primarily used in the chemotherapeutic treatment of malignant brain tumors. However, its clinical application faces significant constraints due to its lipophilicity, low thermal stability, and rapid degradation in physiological environments. To tackle these challenges, our research aimed at the development and detailed characterization of α-cyclodextrin (α-CD) inclusion complexes (ICs) with BCNU employing three different synthesis techniques: co-grinding, cryomilling, and co-precipitation. The selected synthetic methods displayed variations dependent on the technique used, affecting the efficiency, inclusion ratios, and drug-loading capacities, with co-precipitation achieving the most favorable complexation parameters. Structural elucidation through ¹H NMR chemical shifts analysis indicated that only partial inclusion of BCNU occurred within α-CD in ICs produced via co-grinding, while cryomilling and co-precipitation allowed for complete inclusion. Multimodal spectroscopic analyses (FT-IR, UV-Vis, ¹³C CP MAS NMR, and ESI-MS) further substantiated the effective encapsulation of BCNU within α-CD, and systematic solubility assessments via Job’s continuous variation and the Benesi-Hildebrand method revealed a 1:1 host-guest stoichiometry. The ICs obtained were evaluated for BCNU release in vitro at pH levels of 4, 5, 6.5, and 7.4. The mechanism of BCNU drug release was determined to be Fickian diffusion, with the highest cumulative release noted in the acidic microenvironment. These findings collectively validate the effectiveness of α-CD as a functional excipient for the modulation of BCNU’s physicochemical properties through non-covalent complexation. This strategy shows potential for increasing the stability and solubility of BCNU, which may enhance its therapeutic effectiveness in the treatment of brain tumors. Full article