Search Results (2,354)

Background: The key parameters determining the bioavailability of an active pharmaceutical ingredient are its solubility/dissolution rate in physiological fluids and permeability across biological membranes. Highly accurate in vitro prediction of bioavailability is a key issue that typically arises during the development of new drug formulations and the improvement of existing ones. Objectives: The objective of the present work is to study the dissolution/release and permeation of olanzapine (OLZ) from two- and three-component solid dispersions (SDs) with sulfobutylether-β-cyclodextrin (SBE-β-CD) and several pharmaceutical adjuvants as solubilizing agents. Methods: Solid dispersions were prepared by mechanical grinding and characterized with X-ray Phase analysis (PXRD), Fourier Transform Infrared (FTIR) and Raman spectroscopy, Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Results: Raman spectroscopy was shown to be the best for revealing the interactions of OLZ with SBE-β-CD and γ-aminobutyric acid (GABA) in the three-component SD. The kinetic dependences of OLZ release and diffusion through the cellulose membrane were thoroughly described by quantitative parameters and classified according to the drug release mechanism. Significant improvement of release rate, OLZ concentration, and permeation with SDs compared to the pure OLZ was demonstrated. Conclusions: It was shown that the selected dispersions were stable when stored under normal conditions but underwent changes upon exposure to elevated temperature and humidity. The nature of these changes was determined by the properties of the components and their mutual interactions. 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

Paclitaxel is a first-line anticancer drug, but its low water solubility impedes bioavailability. The purpose of this study is to estalish a delivery strategy via carboxymethyl chitosan (CMCS)-encapsulated 6-deoxy-6-mercapto-β-cyclodextrins (dmβCDs)-modified concave cubic gold (CCGs) to achieve PTX release. CCGs were initially synthesized by the one-pot method and further modified by dmβCDs, the dmβCDs can effectively capture PTX molecules, followed by encapsulation with CMCS, and then prepare pH-responsive CMCS/dmβCDs/CCGs nanocarriers after lyophilization. Results indicated that desirable hexagonal CCGs with 50 ± 5 nm size can be obtained by adjusting H₂O₂ and HClO concentration. FT-IR, Raman and XRD spectra had confirmed dmβCDs successfully grafted to the surface of CCGs. Drug loading experiments demonstrated that the nanocarrier encapsulated PTX in amorphous powder or molecular form have a capacity of 55.05 µg/mL. Drug release experiments revealed PTX release from CMCS/dmβCDs/CCGs nanocarriers carrying a typical pH-responsive profile and indicating earlier release in an acidic environment than in a neutral or alkaline environment. The proposed method can be utilized to effectually achieve high-efficiency solubilization and targeted release inside tumor cells of PTX. Full article

Daily exposure to blue light emitted by digital devices has raised concerns about oxidative stress-mediated damage to the ocular surface. Despite growing interest, validated in vitro models to study blue light-induced oxidative stress in corneal epithelial cells remain limited. A reproducible in vitro method was developed using rabbit corneal epithelial (RCE) cells exposed to blue LED light (405 nm). Irradiation parameters were optimized to induce oxidative stress without causing overt cytotoxicity. Cellular viability, intracellular ROS production, and mitochondrial oxidative stress were assessed. The model was validated using reference antioxidants (ascorbic acid and oleuropein), oleuropein formulated in a drug-in-cyclodextrin-in-liposome system (OLE-DCL), and two commercial ophthalmic formulations applied before or after irradiation. Blue light irradiation at 4.57 W/m² for 30 min significantly increased intracellular and mitochondrial ROS levels while preserving cell viability, indicating sublethal photo-oxidative stress. Ascorbic acid effectively suppressed ROS generation, whereas free oleuropein showed reduced efficacy, likely due to photosensitivity. OLE-DCL significantly enhanced antioxidant activity under irradiation. The model also discriminated between protective and restorative treatment strategies. This study establishes a validated in vitro blue light-induced oxidative stress model for corneal epithelial cells, suitable for screening antioxidant compounds, formulations, and application strategies relevant to ocular surface protection. Full article

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