Search Results (678)

Background/Objectives: Ursodeoxycholic acid (UDCA) is a bile acid widely used for the treatment of cholestatic liver diseases; however, its poor aqueous solubility represents a major limitation for the development of oral liquid formulations, particularly in pediatric patients requiring accurate and flexible dosing. This study aimed to develop and characterize a fully solubilized extemporaneous UDCA oral formulation using the ready-to-use vehicle Wagner, with particular emphasis on the role of hydroxypropyl-β-cyclodextrin (HP-β-CD) as a solubilizing excipient. Methods: Phase-solubility studies, Job’s plot analysis, and ¹H NMR spectroscopy were performed to investigate the host–guest interaction between UDCA and HP-β-CD, confirming the formation of a stable 1:1 inclusion complex responsible for a marked increase in drug solubility. The aqueous solubility of UDCA increased from approximately 0.02 mg/mL in water to 31 ± 1 mg/mL in the Wagner base containing HP-β-CD, compared to ~10 mg/mL in the corresponding cyclodextrin-free vehicle. Chemical stability was evaluated using an HPLC method adapted from the European Pharmacopoeia, employing dual detection (refractive index and photodiode array detector) to ensure specificity and stability-indicating capability. Results: The UDCA solution (20 mg/mL) remained chemically stable for at least 4 months under refrigerated (4–8 °C) and room temperature (25 °C) conditions, with only moderate degradation observed at 40 °C. Physical stability studies confirmed the absence of precipitation, phase separation, or significant pH variations under all storage conditions. Conclusions: Wagner-based formulation enabled the development of a stable and homogeneous UDCA oral solution, providing a complementary formulation strategy to conventional suspension-based preparations. This approach represents a robust and patient-oriented strategy for extemporaneous compounding, particularly suitable for pediatric use. Full article

Achieving precise control over anticancer drug release remains one of the key challenges in modern pharmaceutical development, as it directly determines therapeutic efficacy, systemic toxicity, and patient outcomes. This review critically evaluates recent advances in three major formulation strategies: polymeric solid dispersions, cyclodextrin-based inclusion complexes, and metal–organic frameworks (MOFs), with a particular focus on their capacity to tailor anticancer drug release. Over the past decade, polymeric solid dispersions and cyclodextrin-based carriers have played a central role in improving the dissolution and bioavailability of poorly water-soluble anticancer agents, while also enabling modified release profiles through rational formulation design. Increasing structural complexity, including ternary systems and supramolecular assemblies, reflects a shift toward more controllable delivery platforms. In recent years, MOFs have emerged as highly adaptable porous materials capable of supporting controlled and stimuli-responsive release. The integration of imaging agents, magnetic components, and photothermal functionalities has further enabled the design of multifunctional and theranostic platforms. Taken together, these technologies reflect a shift from conventional solubility enhancement toward structurally engineered systems designed to achieve predictable and controlled drug release. Continued advances in material design and formulation strategies are expected to further refine release kinetics and support the development of next-generation anticancer therapies aligned with the growing demand for precision medicine. Full article

Background/Objectives: For the first time, water-soluble encapsulated forms of 20-hydroxyecdysone were synthesized as clathrate complexes with β-cyclodextrin. The derivatives included a ketoxime form (20-NOH), obtained by selective oximation of the C-6 carbonyl, and a triacetate form (3Ac-20E), obtained by regioselective acetylation of the C-2, C-3, and C-22 hydroxyl groups. Methods: The chemical structures of the obtained compounds were confirmed using spectroscopic methods, including ¹H and ¹³C NMR. The Z-configuration of the oxime in 20-NOH was established by the diagnostic upfield shift in the C-5 resonance (δ 36.0 ppm) relative to the parent compound (δ 51.4 ppm). Results: The antioxidant activity was evaluated using FRAP and DPPH assays. The β-cyclodextrin complexes were shown to exhibit significantly higher radical scavenging activity, with IC₅₀ values of <0.05 mg/mL compared to 0.24 mg/mL for the parent 20-hydroxyecdysone (20E). In the FRAP assay, the complexes demonstrated enhanced reducing capacity, with values of 3.452 ± 0.520 AAE/mL for the ketoxime form (20-NOH·β-CD) at a concentration of 0.75 mg/mL and 3.810 ± 0.279 AAE/mL for the acetate form (3Ac-20E·β-CD) at the same concentration, whereas the parent compound did not exceed 0.46 AAE/mL. In both in vitro and in vivo experiments, it was established that the investigated complexes demonstrated hepatoprotective properties, as evidenced by the normalization of biochemical parameters as well as the restoration of liver structure according to ultrasound and histological studies. The ketoxime-derived complex (20-NOH·β-CD) at a dose of 25 mg/kg demonstrates the greatest reduction in transaminase activity and MDA levels, indicating its high efficacy and the presence of an optimal therapeutic dose. In addition, the encapsulated forms demonstrated moderate antifungal activity against Candida albicans and bactericidal activity against four bacterial strains (MIC >10 mg/mL). Conclusions: The obtained results indicate that β-cyclodextrin complexes significantly enhance the biological activity of 20E and highlight the potential of these compounds for pharmaceutical applications. Full article

Here, we present a general statistical-mechanical model able to reconstruct the temperature dependence of the thermodynamic properties of non-covalent host–guest inclusion complexes using a set of molecular dynamics simulations along an isobar. Our approach, applied to $\beta$-cyclodextrin in interaction with E- and Z-dimethomorph as well as a bisphenol A derivative, provides a robust description of the in silico data, able to well reproduce the host–guest binding thermodynamics at every temperature. Full article

The increasing prevalence of drug-resistant microorganisms has prompted research into novel antimicrobial compounds, with 2-thiophene carboxylic acid thiourea derivatives showing promise for future therapeutic applications. However, the poor water solubility of these compounds limits their practical use. This study investigates the formation and characterization of inclusion complexes between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2-thiophene carboxylic acid-halogenated (chlorine-, bromine-, and iodine-) thiourea derivatives, seeking to improve their physicochemical properties. The dynamic light scattering (DLS) measurements and UV-Vis spectroscopy provided information related to thiourea–HPβCD aggregates and stoichiometry. Solid-state inclusion compounds and physical mixtures were prepared in two different molar ratios (thioureas:HPβCD = 1:1 and 1:2), and the morphology of the resulting powders was observed by scanning electron microscopy (SEM). Thermogravimetry (TG) and differential scanning calorimetry (DSC) (TG-DSC) coupled analysis were used to analyze thermal profiles in the temperature range of 25 °C to 600 °C, while the spectral data obtained by Fourier transform infrared spectroscopy (FTIR) provided the characteristic vibrational bands of the pure guest molecules and data corresponding to the structural and chemical changes in the host–guest systems. The structural and thermal analyses revealed significant interactions between the host and thioureas molecules, with evidence of possible interactions involving two cyclodextrin molecules. The results demonstrate the presence of intermediate stoichiometry in the inclusion compounds, with possible enhancement of the therapeutic potential of these thiourea derivatives. Full article

This study explores the formation of inclusion complexes between a newly synthesized N-(2-(butylamino)-2-oxoethyl)-2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxamide with β-cyclodextrin using density functional theory with dispersion correction (DFT-D3) at the B3LYP-GD3/3-21G, 6-31G(d), 6-31G’(d), and 6-311G(d) levels. Two orientations are considered: in Orientation A, the 3-cyano-4-isobutoxyphenyl moiety interacts with the primary hydroxyl rim of β-cyclodextrin, while in Orientation B, the amide side chain faces the wider rim. Complexation energies and thermodynamic parameters are calculated to determine stability. Electronic properties, including HOMO-LUMO energies, and global reactivity descriptors, such as electronegativity (χ), chemical potential (μ), hardness (η), and electrophilicity index (ω), are evaluated. Non-covalent interaction (NCI) analysis is also performed to visualize interaction sites. The results reveal the significant influence of orientation on the host–guest complex stability and electronic properties, providing valuable insights into cyclodextrin-based encapsulation systems. The study provides a computational blueprint for engineering cyclodextrin-based bio-functional systems, where orientation-controlled inclusion governs stability, reactivity, and performance. This can significantly impact the development of smart drug delivery systems, biosensors, and multifunctional biomaterials in modern bioengineering. Full article

This study evaluates β-cyclodextrin (β-CD) and malonic acid functionalized pine sawdust biochar for organic pollutant removal, benchmarking efficacy against commercial Norit GSX activated carbon for sustainable water treatment. Characterization revealed that β-CD modification successfully developed porous structures, with Sawdust Activated Carbon (SDAC) and Norit GSX Activated Carbon (GSXAC) achieving Brunauer–Emmett–Teller (BET) surface areas of 438.36 m²/g and 1223.79 m²/g, respectively. Adsorption kinetics and isotherm studies demonstrated the superiority of β-CD-modified materials over traditional acid-functionalized variants. The adsorption kinetics were exceptionally well-described by the Pseudo-Second-Order model R² > 0.99, indicating that the process is governed by chemical interactions rather than simple physical attachment. In contrast, the Pseudo-First-Order and Elovich models provided poor descriptions of the system (R² = 0.54 and 0.11, respectively). An isotherm analysis further confirmed the heterogeneous nature of the SDAC surface, with the Freundlich model exhibiting an excellent fit (R² > 0.99) and an n value of 0.79. For GSXAC, the Freundlich model also outperformed the Langmuir model, yielding a K_F of 441.72 mg/g and n = 0.77, reflecting high adsorption intensity on a heterogeneous surface. The comparative advantage of β-CD is in line with its unique truncated cone structure, which is consistent with guest–host inclusion complex formation, multi-modal hydrogen bonding, and enhanced pH resilience. These findings validate β-CD-modified sawdust-derived adsorbents as potential, sustainable, high-capacity alternatives to industrial-grade carbons. Full article

Background: Baicalein (BA) is a poorly soluble flavonoid with limited oral bioavailability. This study aimed to enhance the solubility and nasal absorption of the compound using a dual-carrier system that combines cyclodextrin inclusion complexes and thermosensitive hydrogels. Methods: The inclusion complexes of BA with hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutyl-β-cyclodextrin (SBE-β-CD), namely BA-HP-β-CD and BA-SBE-β-CD, were prepared via solution stirring and characterized by solubility, dissolution, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis-differential scanning calorimetry (TG-DSC), and Madin-Darby canine kidney (MDCK) cell permeation. The optimal complexes were incorporated into chitosan/β-glycerophosphate thermosensitive hydrogels (BA/HP-Gel and BA/SBE-Gel), followed by evaluations of gelation properties, in vitro release, and in vivo pharmacokinetics in rats. Results: The water solubility of BA-HP-β-CD and BA-SBE-β-CD increased 572 and 582 times, with MDCK permeability enhanced by 5.3 and 2.9 times, respectively. Both hydrogels showed rapid solution-gel transition at nasal temperature and sustained release. Following intranasal administration, BA/HP-Gel and BA/SBE-Gel achieved relative bioavailabilities of 623.5% and 697.8%, respectively, compared with BA-Gel. Conclusions: The dual-carrier platform effectively improved BA solubility, permeability, and nasal bioavailability, offering a promising strategy for nasal delivery of poorly soluble drugs. Full article

Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. Full article

Achieving stable dispersion and sustained antibacterial activity of natural bioactive compounds in bio-based packaging remains challenging. In this study, chitosan (CS) films incorporating a β-cyclodextrin–curcumin inclusion complex (Cur/β-CD) were developed to improve film properties and the refrigerated preservation of sea bass. The CS/Cur/β-CD films were prepared by one-step solution casting without intermediate isolation or purification. The inclusion conditions were optimized, and the resulting films were evaluated in terms of tensile strength (TS), elongation at break (EAB), and water vapor permeability (WVP). Among the tested formulations, the film prepared at a Cur:β-CD ratio of 1:1, 40 °C, and 1 h (1:1 40 °C 1 h) showed the best overall performance in TS, EAB, and WVP. It was therefore selected for subsequent structural characterization, antibacterial evaluation, and preservation testing. The 1:1 40 °C 1 h film exhibited a 156% increase in tensile strength and a 28.5% decrease in water vapor permeability compared with the neat CS film. The composite film exhibited measurable diffusion-based antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). During the 8 d refrigerated storage period, the film suppressed total viable counts (TVC), slowed the increase in pH, and retarded total volatile basic nitrogen (TVB-N) accumulation, thereby maintaining acceptable microbiological quality throughout the observation period. Compared with the unwrapped, PE, and CS-film control groups, the treated samples showed better preservation performance over the tested storage period. Overall, the incorporation of Cur/β-CD provides a simple strategy for improving the mechanical strength, moisture barrier properties, antibacterial activity, and preservation performance of CS films during refrigerated storage, highlighting their potential for active packaging of chilled aquatic products. Full article

Baicalin is a natural compound sourced from Scutellaria baicalensis which possesses various biological activities. To date, a large amount of research has been conducted on the antibacterial activity and related mechanisms of baicalin, making it a promising candidate for new broad-spectrum antibacterial drugs. However, the solubility of baicalin is limited. To improve its solubility and overcome the clinical application bottleneck, researchers have developed various solubilization techniques. Therefore, this article introduces the biological characteristics of baicalin; explores its effects as an antibacterial agent on bacterial biofilms, quorum sensing, virulence factors, inflammatory responses, and the immune system; and discusses the applications of nano-carrier loading technology, cyclodextrin inclusion technology, metal ion coordination and organometallic complexation technology, and dynamic covalent hydrogel assembly technology in improving the solubility of baicalin, thereby enhancing its antibacterial activity. Full article

The clinical utility of the anticancer drug camptothecin (CPT) is limited by its poor aqueous solubility and instability in the bloodstream, hindering bioavailability and efficacy. This study explores the complexation of CPT with carboxymethyl-beta-cyclodextrin (cmβCD) to overcome these limitations. Fluorescence spectroscopy and molecular modeling demonstrated 1:1 inclusion complexes, with stability constants governed by electrostatic interactions that were inversely correlated with pH. To validate this effect, a cationic amino-beta-cyclodextrin (amβCD) was used as a mechanistic control, revealing that Coulombic forces significantly modulate binding strength and stoichiometry. Crucially, cmβCD enhanced CPT solubility by up to 11-fold at 14 × 10⁻³ moldm⁻³, enabling a 385-fold increase in drug loading into liposomal carriers compared to the cyclodextrin-free system. Fluorescence-based release studies indicated high liposomal stability at physiological pH and partial CPT release under acidic conditions. Furthermore, CPT-loaded liposomes demonstrated cytotoxicity against cancer cell lines, particularly BT-474, with IC₅₀ values generally comparable to or slightly higher than those of free CPT and the CPT:cmβCD complex, likely due to the distinct lysosomal cellular uptake pathway. This work highlights cmβCD complexation as a promising strategy to enhance CPT solubility and liposomal loading for improved drug delivery. Full article

Background/Objectives: Essential oils (EOs) have multi-target antifungal activity, but their translation is limited by volatility and poor aqueous dispersibility. Randomly methylated β-cyclodextrin (RAMEB) inclusion may enhance effective exposure and thereby alter susceptibility, stress responses, and biofilm outcomes in a species-dependent manner. This study quantified species-specific planktonic and biofilm susceptibility to four EOs and their RAMEB complexes across clinically relevant Candida species. Methods: Lavender (L), lemon balm (B), peppermint (P), and thyme (T) oils and their RAMEB complexes (RL, RB, RP, and RT) were tested against C. albicans and non-albicans Candida. Susceptibility thresholds were used to derive phase plasticity metrics. Functional inhibition was assessed via planktonic metabolism/viability and established biofilm metabolism/viability/biomass. Mechanistic signatures were captured by ROS/RNS measurements and a qPCR analysis of antioxidant genes (CAT1, GPX1, and SOD1) was performed. Mixed-effects models and multivariate/unsupervised and interpretable classification approaches (k-means, PCA, and CRT) were used to integrate endpoints and stratify response phenotypes. Results: Susceptibility thresholds were strongly species-structured (lowest MIC₉₀/EC₁₀ for C. albicans; higher thresholds and broader sublethal windows in non-albicans species). RAMEB complexation produced formulation-dependent shifts in efficacy, with RT emerging as the most consistent broad-spectrum inhibitory condition across compartments. Biofilm biomass was comparatively insensitive even when viability was suppressed, indicating a decoupling of structural biomass from biocidal activity. Mechanistic signatures were broadly conserved across species and linked to antioxidant-program engagement, with CAT1-related rules contributing to responder/tolerant classification. Conclusions: Integrating MIC/EC plasticity with functional and mechanistic markers supports the rational selection of EO formulations; RAMEB complexation, particularly RT, prioritizes candidates for further pharmaceutical optimization while highlighting species-specific vulnerabilities. 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

The paper presents the synthesis of new naphthyl-containing derivatives of thiosemicarbazide and thiourea, their water-soluble inclusion complexes with β-cyclodextrin, as well as an assessment of their potential antiviral and hemorheological activity. As a criterion for the specific antiviral effect of new compounds, their chemotherapeutic indices were calculated using predictive analytics tools driven by artificial intelligence and molecular docking methods. Molecular docking studies with three protein targets PknB (2FUM), DprE1 (6HEZ), and InhA (1ENY) confirmed strong and specific ligand–protein interactions. The effects of structural features of new compounds on the rheological characteristics of blood were considered, and the most promising samples were identified for further in-depth in vitro study of their specific biological activity. The performed thermoanalytical study showed that the structure of the included ligand, as well as the shape of the receptor, significantly affect the thermal stability and kinetic parameters of the decomposition of the inclusion complex. In silico evaluation of the newly synthesized compounds revealed promising biological activity profiles, with all compounds demonstrating predicted antimycobacterial and antituberculosis potential. In silico analysis of the newly synthesized compounds revealed favorable biological activity profiles, with all candidates demonstrating predicted antimycobacterial and antituberculosis potential. Full article