Search Results (2,350)

Bee pollen is a natural product with multifunctional properties, containing abundant bioactive compounds, especially phenolic acids and flavonoids, which are largely responsible for its antioxidant and antimicrobial activities. In this study, the bioactive composition, antioxidant capacity, encapsulation efficiency, antimicrobial activity, and gastrointestinal stability of bee pollen extract (PE) were investigated. The pollen extract exhibited high total phenolic (2817 mg GAE/100 g) and flavonoid contents (5255 mg QE/100 g), along with strong antioxidant activity (DPPH: 4305 mg TE/100 g; CUPRAC: 3685 mg TE/100 g). To improve the stability and bioaccessibility of phenolic compounds, PE was encapsulated using β-cyclodextrin (BCD) at different weight ratios. Among the formulations, the PE:BCD ratio of 1:2 showed the highest encapsulation efficiency (64%) and favorable physicochemical properties, including higher particle size and more negative zeta potential values, indicating good colloidal stability. Antimicrobial activity was evaluated for PE, BCD-only, and the selected PE-loaded formulation (1:2, w:w). Encapsulation led to a modest reduction in antimicrobial activity compared to free PE (6.25–50 mg/mL); however, the encapsulated formulation still exhibited considerable antibacterial effects against both Gram-positive and Gram-negative strains (25–50 mg/mL). Furthermore, in vitro gastrointestinal digestion indicated that BCD encapsulation substantially enhanced the bioaccessibility of total phenolics (81%) and antioxidant capacity (DPPH: 48%; CUPRAC: 76%), particularly during the intestinal stage. Phenolic profiling showed that chlorogenic acid and quercetin derivatives remained relatively stable throughout digestion. Overall, encapsulation with BCD effectively safeguarded pollen phenolics, improved their gastrointestinal stability, and increased bioaccessibility, highlighting the potential of encapsulated bee pollen as a functional food ingredient or nutraceutical. Full article

The photocycloaddition (PCA) of chalcones represents an important reaction pathway for accessing substituted cyclobutanes, which is a molecular framework with utility in synthetic chemistry, materials science, and medicine. In the past, our group has demonstrated the utility of the large cavity of γ-CD as a container for encapsulating two photo reactants for directing the PCA of several classes of aryl alkenes with high stereo- and regioselectivity: the cavitand-mediated photodimerization (CMP) approach. The CMP of chalcones reported in this work further demonstrates the effectiveness of this approach as high yields of dimers were observed in the photoreactions, while they were non-reactive in the solid state and yielded only the isomerization product in homogeneous media. The γ-CD CMP of chalcones yielded predominantly dimerized products in very good to high yields (>70%), composed of a mixture of three dimers in different proportions with syn HH as the major product. Computational analysis of the ground state complex structures revealed a strong correlation between the stability of the complex and predominance of the stereoisomer in the mixture. Further insights were deduced from temperature-dependence studies, which showed a shift in dimer selectivity tending towards a single stereoisomer. Full article

Background/Objectives: Inclusion complexes among drugs and cyclodextrin-modified polymers are a topic of recent interest in pharmaceutical research and industry as they might expand the solubility, bioavailability, and stability of the guest molecules. Polyurethanes derived from cyclodextrins show some biomedical applications. In this study, two cross-linked polyurethane networks based on hydroxypropyl-β-cyclodextrin (HPβCD) and polyethylene glycols (PEG 2000 or PEG 6000) were synthesized with NCO/OH molar ratio 4.3 and 6.3 by the typical two-step polymerization method. Methods: Inclusion complexes of clotrimazole (CLOT) with two HPβCD-modified polyurethane networks and their corresponding physical mixtures were prepared using kneading methods and physical mixing in a 1:6 weight ratio of CLOT:HPβCD. Results: Obtained prepolymers, previously end-capped with isocyanate groups forming urethane links with HPβCD, which were confirmed by FTIR analysis. TGA results indicate a slight increase in thermal stability of the prepared complexes. The characteristic endothermic peak of the CLOT at around 145.90 °C did not appear in the DSC curve of the drug-loaded inclusion complexes. The XRD patterns of physical mixtures showed specific peaks corresponding to pure clotrimazole. SEM micrographs confirmed an elliptical/spherical- and plate-shaped particles without phase segregation, indirectly confirming that CLOT is not separately present due to inclusion into HPβCD and entrapment into polyurethane networks. Novel complexes PUR2/HPβCD-CLOT-IC and PUR3/HPβCD-CLOT-IC were applied as drug carriers, and diffusion-controlled kinetics of CLOT release were best described using Higuchi model. Conclusions: The obtained in vitro results showed surprisingly slow/prolonged clotrimazole release from modified polyurethane networks due to the significant influence of NCO/OH molar ratio and the chosen polyol soft segments chain length with potential in vivo applications. Full article

This study evaluated the effect of water vapor generated by fresh-cut mango (Mangifera indica) on the release of β-carotene from β-cyclodextrin complexes (β-C:β-CD) under stored Modified Atmosphere Packaging (MAP) and to demonstrate β-carotene stabilization and passive–active packaging behavior under MAP conditions. Containers with fresh-cut mangoes, with and without MAP (4% O₂, 6% CO₂, 90% N₂), were prepared for monitoring over 6 days at 4 °C. β-C:β-CD complexes were incorporated into the lids of containers. The physicochemical, relative humidity, antioxidant, erythroprotective, microbiological, and biofunctional qualities of freshly cut mangoes during storage were analyzed. Active metabolic respiration of plant tissue led to a progressive decrease in O₂ and an increase in CO₂ in sealed containers, a phenomenon intensified by cutting, high humidity, and the system’s limited gas permeability. Application of MAP effectively modulated this microenvironment, reducing respiration rate, water loss, acidification, and the degradation of bioactive compounds. Compared to treatments without MAP, mangoes stored under modified atmosphere showed greater color stability, a slower rate of change in pH and titratable acidity, less loss of antioxidant activity and phenolic compounds, and significant preservation of erythroprotective capacity. Furthermore, MAP maintained microbial counts within the limits established by current regulations until the sixth day of storage. The encapsulation of β-C in β-CD effectively protected its bioactivity from oxidation, especially under MAP, although its release into the food matrix was limited, suggesting a predominantly passive behavior of the active packaging system. Overall, the results demonstrate that the combination of MAP constitutes a promising strategy for extending the shelf life and biofunctional stability of fresh-cut mangoes and β-C into the complex. Full article

This study assesses the stability, in vitro bioaccessibility and potential bioavailability, and in vivo genotoxicity and toxicity of polyethylene glycol–soy lecithin (PEGSL-ACG-NSps) or β-cyclodextrin–soy lecithin (βCDSL-ACG-NSps) nanosuspensions (NSps). Both formulations exhibited initial particle sizes below 130 nm and PDI values below 0.3. Under simulated gastrointestinal conditions, PEGSL-ACG-NSps preserved structural integrity, with only a moderate size increase (~239 nm) in the intestinal phase and controlled release of acetogenins (ACGs); in contrast, βCDSL-ACG-NSps destabilized considerably (size > 500 nm) and released ACGs rapidly. Consistently, βCDSL-ACG-NSps achieved higher in vitro bioaccessibility and a potential bioavailability (up to 95% from post-digestion recovery). In contrast, PEGSL-ACG-NSps displayed a more gradual release profile (up to 55%). In vivo toxicity tests in mice showed no significant genotoxic or cytotoxic effects for either formulation, even at high doses. These findings suggest that selecting appropriate food-grade stabilizing polymers is crucial for optimizing NSps for the oral delivery of ACGs as therapeutic agents. Full article

Background/Objectives: Poor aqueous solubility and limited nasal permeability remain key challenges in the intranasal delivery of carbamazepine. In this study, biocompatible bovine serum albumin nanoparticles functionalized with sulfobutyl-β-cyclodextrin (SβCD-BSA NPs), comprising individually cytocompatible components with confirmed physical interactions), were formulated for intranasal delivery of carbamazepine (CBZ). Methods: The ethanolic desolvation method was utilised for the preparation of the nanoparticles, with the functional moiety incorporated during nanoparticle preparation. The effects of different molar ratios of SβCD-BSA and different ethanol volume ratios were studied. For crosslinking, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), a non-toxic crosslinker, was utilised. To determine the role of the SβCD, two preparation samples were formulated, with and without SβCD. Results: The formulation without SβCD incorporation had a mean particle size of 125 ± 0.64 nm, polydispersity index (PDI) of 0.34, encapsulation efficiency (EE%) of 61.5 ± 1.40%, and drug-loading ratio (DL%) of 31.9 ± 1.50%. Conversely, the SβCD-functionalized formulation showed a mean particle size of 128 ± 2.12 nm, PDI of 0.21 ± 0.03, EE of 64.6 ± 0.35%, and DL of 34.28 ± 1.60%. Statistical analysis revealed that the incorporation of SβCD resulted in a statistically significant increase in both DL% and EE% (p < 0.05). Conversely, the observed differences in particle size and PDI were not statistically significant (p > 0.05). This addition provides precise context regarding the comparability of the formulations while highlighting SβCD’s functional benefits in solubility and permeation. The interaction between CBZ and SβCD-BSA was confirmed using Fourier-transform infrared spectroscopy. Lastly, the prepared formulations were characterised by their physicochemical attributes and in vitro biopharmaceutical studies. It was discovered that SβCD plays a dual role, enhancing the solubility of CBZ in one scenario while promoting its nasal permeation, suggesting its potential use in epilepsy treatment. Conclusions: These findings highlight the potential of SβCD-BSA NPs as a versatile pharmaceutics platform for the intranasal delivery of poorly soluble CNS drugs. Full article

Ionotropic alginate-based hydrogelation by divalent metal interaction has been employed to study the effect that different types of ions might have on gel formation. In this regard, EPR and IR spectroscopies, as well as rheology techniques, have been used to evaluate the influence of divalent cations on gel formation, and at the same time to assess host–guest interactions. Alginate was functionalized with TEMPO moieties; therefore, TEMPO-alginate system was taken as a reference. The novelty of this study consists of using a mixture of adamantyl-TEMPO-functionalized alginate and β-cyclodextrin linked through 1,3-diaminopropane to assess the host–guest interactions in functionalized gels. The properties of divalent cations considered in this study (Ba²⁺, Ca²⁺, Sr²⁺, Zn²⁺) were proven by changes in spectral parameters of paramagnetic moieties, while the viscoelastic moduli as functions of shear strain and frequency were evaluated through rheology measurements. Overall, the information obtained from these investigations has shown that the properties of the alginate gels are influenced both by the type of divalent cation used for complexation and by the host–guest interactions. The results show that the type of the cation significantly affects gel strength; therefore, Ba²⁺ forms the strongest gel, while Zn²⁺ the least resistant. Additionally, a high immobilization of the spin-labeled probes has been obtained by the addition of tosylated β-cyclodextrin in the alginate gel network containing Ba²⁺ ions. Full article

Post-harvest deterioration in strawberries is an urgent and critical issue that requires significant attention. Glycerol monolaurate (GML), a broad-spectrum food-grade antimicrobial agent, faces limited applicability due to its poor water solubility. In this study, a confined encapsulation strategy was employed to encapsulate GML within hydroxypropyl-γ-cyclodextrin (HPγCD), which improved the physicochemical properties of GML and enhanced its stability in the environment. The fiber morphology was observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), confirming the presence of a uniform, non-nodular core–shell structure. The Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) validated the successful encapsulation of GML within the cavity of HPγCD. Thermogravimetric analysis (TGA) demonstrated that the thermal stability of the core–shell system was significantly improved. In vitro release followed first-order kinetics (R² = 0.9842), with 79.5% of GML released over 68 h. The DPPH and ABTS assays demonstrated that PLA/GML-HPγCD NF exhibited sustained radical scavenging activity (p < 0.05, ANOVA). Compared to GML-HPγCD NF, PLA/GML-HPγCD NF exhibited prolonged antibacterial activity against Escherichia coli and superior antifungal efficacy in strawberry preservation. Meanwhile, PLA/GML-HPγCD NF significantly reduced lesion diameter and weight loss while maintaining hardness, total soluble solids, and vitamin C content over 8 days of storage. In conclusion, these characteristics highlighted the potential of P/G-HPγCD NF as a promising active packaging material for extending the shelf life of perishable fruits. Full article

This review critically examines how cyclodextrins modulate regulated cell death pathways and the implications for immunometabolism and therapeutic translation. Increasing evidence, however, indicates that cyclodextrins exert intrinsic biological activity by modulating cellular lipid homeostasis, membrane organization, and intracellular trafficking. In recent years, these properties have positioned cyclodextrins as unexpected regulators of regulated cell death (RCD) pathways, with broad implications for immunometabolism and therapeutic innovation. This review provides a comprehensive overview of the mechanisms by which native and chemically modified cyclodextrins influence major forms of regulated cell death, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis, and necroptosis. Particular attention is given to cholesterol sequestration, lipid raft disruption, lysosomal cholesterol mobilization, and transcriptional reprogramming via pathways such as TFEB (transcription factor EB) and AMPK (AMP-activated protein kinase), which collectively shape cell fate decisions. We further examine how cyclodextrin-mediated modulation of RCD intersects with immune metabolism, especially macrophage polarization and inflammasome activity, thereby influencing inflammatory responses and disease progression. Translational implications are discussed across diverse pathological contexts, including cancer, cardiovascular diseases, neurodegenerative disorders, inflammatory and autoimmune conditions, infectious diseases, and lysosomal storage disorders. Finally, emerging cyclodextrin-based delivery platforms, ranging from inclusion complexes to nanoparticles and polymeric systems, are evaluated with respect to their ability to achieve targeted modulation of cell death while minimizing off-target toxicity. Importantly, we critically discuss dose-dependent cytotoxicity, sterol depletion–related adverse effects, and formulation-dependent variability, which currently limit the clinical translation of cyclodextrin-mediated cell death modulation. By integrating mechanistic insights with pharmaceutical formulation strategies, this review delineates key challenges and opportunities for the rational design of cyclodextrin-based therapeutics. Overall, this review highlights cyclodextrins as bioactive modulators rather than inert carriers, underscoring their potential to inspire novel pharmacological strategies that integrate drug delivery, immunometabolism, and regulated cell death. Full article

Allyl isothiocyanate (AITC) is a potent natural antimicrobial agent; however, its practical application is severely hindered by its extreme volatility and pungent, irritating odor. In this study, AITC inclusion complexes (AITC@β-CD) were successfully fabricated via a co-precipitation strategy using β-cyclodextrin (β-CD) as the host matrix. Physicochemical characterizations, including FTIR, SEM, and XRD, confirmed the successful integration of AITC into the β-CD framework, inducing a crystalline phase transition from a cage-type to a channel-type structure. TGA demonstrated a substantial enhancement in thermal stability, with the maximum decomposition temperature shifting to 330 °C. This indicates that the spatial confinement within the channel-type lattice acts as a robust molecular shield that minimizes premature volatilization. Notably, water contact angle measurements revealed that the complexes attained a modulated surface wettability (89.0°), attributed to the structural rearrangement of surface hydroxyl groups. This modification ensures that the material remains compatible with aqueous food matrices while notably masking the unpleasant sensory attributes of pure AITC. Antibacterial assays against the standard indicator strain Escherichia coli (E. coli) confirmed that the encapsulation process preserved the intrinsic bioactivity of the guest, exhibiting comparable inhibitory zones to free AITC. Furthermore, the complexes maintained high inhibitory efficacy against indigenous microbial populations from spoiled fruits. These findings suggest that β-CD encapsulation effectively stabilizes AITC through guest-induced co-crystallization and enhances its consumer acceptability, providing a versatile and efficient strategy for sustainable food preservation. Full article

Gene delivery/administration and, in particular, small interfering RNA (siRNA) delivery represent a therapeutic challenge, though very effective carriers have yet to be identified. Cyclodextrins (CDs) are cyclic oligosaccharides with unique host–guest inclusion capabilities, widely recognized in the pharmaceutical field for their ability to enhance drug solubility and bioavailability. Their excellent biocompatibility and chemical versatility make them powerful building blocks for the design of supramolecular nanovectors (NVs). Thanks to their facility of functionalization, CDs are highly versatile and have found numerous applications across various fields. In this context, CD-based NVs are currently explored as non-viral agents to transport and release siRNA. Recent studies suggest that self-assembled NVs based on CDs can improve the transfection and safety of siRNA delivery. This review provides a comprehensive overview of the most recent advances in the design of NVs based on CDs and their use for siRNA delivery, discussing the role played by structural differences and chemical functionalization in the context of encapsulation and release. Full article

Background: Menopause is characterised by a decline in oestrogen levels, leading to physical and psychological symptoms that significantly affect quality of life. Current parenteral oestradiol ester therapies, while effective, are often associated with side effects due to their oil-based formulations, including injection-site reactions and immune responses. Methods: In this study, we developed a water-soluble, polyethylene glycol cross-linked β-cyclodextrin (PEG–β-CD) polymer-based system for parenteral oestradiol delivery and evaluated its biocompatibility, solubility enhancement, immune compatibility, and pharmacokinetics. Results: Cytotoxicity assays using NIH-3T3 fibroblasts and RAW 264.7 macrophages showed minimal toxicity up to 10% (w/w). Phase-solubility studies demonstrated a significant increase in oestradiol solubility with the PEG–β-CD polymer, surpassing that of β-cyclodextrin or PEG alone. Dynamic light scattering and FTIR analyses confirmed successful complex formation, with submicron particles averaging 271 nm and physical incorporation of oestradiol into the polymer matrix. Macrophage activation assays and RT-qPCR analyses indicated an absence of immunogenic responses or pro-inflammatory cytokine induction. In vivo toxicity testing in Galleria mellonella larvae confirmed safety, while pharmacokinetic studies in Wistar rats revealed rapid initial absorption followed by stable, low-level serum concentrations comparable to those of commercially used oestradiol esters. Conclusions: These findings indicate that the PEG–β-CD polymer–oestradiol complex provides a safe, water-based alternative to traditional oil-based injections, with the potential to reduce side effects and improve patient compliance in postmenopausal hormone therapy. Full article

Isoflavones are plant-derived polyphenols with broad biological activity; however, their application in topical formulations is limited by poor aqueous solubility. The aim of this study was to enhance the aqueous solubility of formononetin using a solvent-free hot-melt extrusion (HME) approach and to enable its incorporation into a hydrogel formulation suitable for skin delivery. Amorphous formononetin-based systems were prepared by HME using polymeric carriers and hydroxypropyl-β-cyclodextrin, with and without prior inclusion complex formation. The resulting formulations were characterized using XRPD, DSC, and FT-IR/ATR to assess amorphization and intermolecular interactions. Aqueous solubility and skin permeability were evaluated using solubility testing, PAMPA, and Franz diffusion cells. The optimized amorphous system exhibited a substantial increase in apparent aqueous solubility compared to crystalline formononetin while maintaining comparable permeability. Cyclodextrin–formononetin interactions were effectively generated during the extrusion process, rendering pre-inclusion unnecessary. The selected system was successfully incorporated into a hydrogel matrix. This study demonstrates that solvent-free HME combined with cyclodextrins is an effective strategy for improving formononetin solubility and enabling its application in hydrogel-based topical delivery systems. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a form of fatty liver disease characterized by fat accumulation, hepatic inflammation, and fibrosis. Lysophosphatidylethanolamine (LPE), a partially deacylated product of phosphatidylethanolamine, plays significant roles in anti-inflammatory responses and mitochondrial homeostasis. Although serum LPE levels are reduced in patients with MASH, the underlying mechanisms remain unclear. In this study, we investigated LPE metabolism using liquid chromatography–tandem mass spectrometry and protein expressions in MASH mice. Male C57BL/6J mice were fed a high-fat, high-cholesterol, and cholic acid diet, along with 2% hydroxypropyl-β-cyclodextrin in drinking water (HFCC/CDX) for three weeks to induce MASH. LPE was primarily distributed in the liver and kidneys, with lower levels in the white adipose tissue. HFCC/CDX mice exhibited accumulation of cholesterols and oxidized triglycerides, accompanied by inflammation and fibrosis in the liver. In the plasma and liver of HFCC/CDX mice, most LPE species were decreased and showed negative correlations with hepatic inflammation, with the exception of LPE 18:1. Mechanistically, enhanced degradation of LPE to glycerophosphorylethanolamine was associated with upregulation of Pnpla6/7 in the liver. These findings suggest that Pnpla6/7-driven LPE catabolism is contributing to LPE depletion. This study provides a new perspective to understand the association between disrupted phospholipid metabolism and MASH pathogenesis. Full article