Search Results (1,197)

Background: Pulmonary drug delivery represents a promising approach for the potential localised treatment of respiratory of non-small-cell lung cancer (NSCLC). However, the efficient delivery of poorly water-soluble drugs remains challenging due to limited solubility and inadequate aerodynamic performance. This study aimed to develop and characterise inhalable dry powder formulations of zinc diethyldithiocarbamate (Zn(DDC)₂) complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) for potential pulmonary administration. Methods: Formulations were prepared by freeze-drying and spray-drying, with leucine incorporated at 0%, 5%, and 10% w/w. Formulations were prepared via freeze-drying and spray-drying with leucine incorporation (0%, 5% and 10% w/w) to evaluate their physicochemical properties, flowability and aerodynamic performance. Results: Spray-dried formulations exhibited significantly lower densities (as low as 1.03 ± 0.71 g/cm³), enhanced flowability, improved aerosolisation and higher fine particle fraction (FPF) values (up to 40.12 ± 0.60%) compared to freeze-dried powders (20.03 ± 2.79%). The incorporation of leucine further reduced powder density down to 0.72 ± 0.34 g/cm³ and increased surface corrugation as shown in SEM images, improving aerosolisation performance, with FPF values up to 76.77 ± 1.18%. Next Generation Impactor (NGI) analysis confirmed that leucine-containing formulations exhibited a greater proportion of particles within the respirable aerodynamic diameter range (1–5 μm), suggesting suitability for deep lung deposition. Conclusions: These results demonstrate that spray-dried Zn(DDC)₂–cyclodextrin powders, particularly those modified with 10% leucine, offer excellent potential for pulmonary delivery in NSCLC therapy. Further in vivo studies are warranted to evaluate therapeutic efficacy and safety. Full article

Background: Oromucosal films are thin polymeric dosage forms designed to hydrate rapidly in the oral cavity and enable local or systemic drug delivery. Their performance depends on coupled processes including wetting, swelling, polymer relaxation, matrix softening, and structural failure. Because these phenomena depend strongly on the formulation composition and polymer-network organization, a mechanistic framework linking conventional characterization data to film performance is needed. This study aimed to develop a Madelung-type multifractal swelling–disintegration–release-readiness model for chitosan/hydroxypropyl methylcellulose (HPMC) films and to examine its relevance using a twelve-formulation experimental series. Methods: Twelve films based on chitosan (film-forming polysaccharide), HPMC K-4M (hydrophilic swelling polymer), glycerin (plasticizer), and starch (disintegrant) were prepared via solvent casting. The films were characterized for loss on drying, surface pH, mass and thickness uniformity, wetting time, swelling behavior, structural-disintegration onset, elongation response, rupture resistance, folding endurance, and surface roughness. The proposed model described water uptake, swelling-front motion, matrix integrity, local release-readiness activation, and hydration-induced loading as coupled fields across the film thickness. Results: Formulation markedly influenced hydration behavior, mechanical performance, structural stability, and surface morphology. Films F2 and F7 emerged as the most promising complementary unloaded matrix platforms for future active-compound incorporation and experimental release evaluation. F2 behaved as a high-swelling, mechanically stable starch-free matrix, whereas F7 combined faster wetting, starch-assisted structural destabilization, and favorable flexibility. Conclusions: This framework provides a quantitative link between empirical film characterization and formulation-level mechanistic interpretation. It translates conventional characterization parameters into descriptors related to the apparent water penetration, swelling capacity, matrix-failure tendency, mechanical suitability, and structural heterogeneity. The present results support candidate selection for future Active Pharmaceutical Ingredient-loaded studies but do not constitute validation of drug-release kinetics. Full article

The topical application of ferulic acid (FA) is limited by its low solubility and high susceptibility to oxidation. To overcome these limitations, the multicomponent system Cicloferulic^® (CF) was developed by mixing FA, hydroxypropyl β-cyclodextrin (HPβ-CD), and polyvinylpyrrolidone K30 (PVP K30), which demonstrated greater safety and antioxidant efficacy than FA alone. The physicochemical characterization of FA, CF, and their components showed greater thermal stability and reduced crystallinity of CF, indicating the formation of the system. In cytotoxicity assays on HaCaT cells, FA maintained cell viability only up to 500 µg/mL, while CF maintained viability even at 10.000 µg/mL, demonstrating 20 times greater safety than FA. In cellular antioxidant activity assays, FA and CF showed similar effects at low concentrations. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, CF and FA reduced more than 70% of DPPH; however, CF contains only 12% FA, indicating an eightfold greater efficiency than FA. Formulations containing FA and CF increased the Sun Protection Factor (SPF) in vitro, even with a 50% reduction in UV filters. However, they did not stabilize formulations with intrinsically photolabile UV filters. In release studies, FA exhibited rapid flow, while CF promoted a modified release profile. Thus, CF stands out as an innovative, multifunctional system that can improve the stability, safety, and efficacy of FA for topical applications. Full article

3-Decen-2-one is a promising natural potato sprout suppressant, but its high volatility, poor stability and low water solubility severely restrict its practical application. To overcome these drawbacks, a 3-decen-2-one/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex with a 1:1 host–guest molar ratio was successfully prepared via the co-evaporation method, and the stability constant was calculated to be 596.43 M⁻¹ by phase solubility studies. Molecular modeling demonstrated that the inclusion complex was primarily stabilized by van der Waals interactions, and the optimal binding conformation was that the alkyl chain of 3-decen-2-one inserted into the cavity from the wider rim of HP-β-CD. The inclusion complex was further characterized by ¹H NMR, FT-IR, TG, and SEM. 3-Decen-2-one showed a better water solubility, thermal stability and release properties after complexation. In the potato storage evaluation, the complex exhibited greater sprout inhibition than free 3-decen-2-one; effectively reduced weight loss, the respiration rate, and MDA accumulation; and maintained a higher Vc and lower reducing sugar levels. Therefore, the obtained inclusion complex is a promising approach to stabilize and achieve the sustained release of 3-decen-2-one as a natural sprout inhibitor for potato storage. Full article

In this work, we develop a coupled multiphysics model that integrates polymer carriers exhibiting time-dependent thixotropic structural recovery with Darcy flow, linear Biot poroelasticity and advection–diffusion transport in a spherically symmetric, isotropic and homogeneous tissue domain. The formulation explicitly links rheological evolution to pressure-driven flow, interstitial deformation and solute transport through a unified framework, enabling systematic prediction of post-injection behavior. Unlike conventional approaches that assume constant carrier properties, the present model incorporates a time-dependent viscosity evolution, capturing the transition from an initially shear-thinned state to a recovered, highly viscous structure. Numerical simulations using hydroxypropyl methylcellulose and methotrexate parameters as representative components demonstrate that rapid post-injection viscosity recovery suppresses pressure-driven transport and diffusion, thereby enhancing local drug retention near the injection site. A systematic sensitivity analysis identifies the equilibrium viscosity as the dominant parameter controlling spatial localization, whereas tissue mechanical properties exert a comparatively minor influence. An effectiveness metric based on the Kullback–Leibler divergence reveals a tumor-size-dependent trade-off between spatial coverage and retention. The proposed framework thus introduces a predictive tool for analyzing coupled rheological-transport interactions and for the rational design and optimization of thixotropy-enhanced local chemotherapy strategies. Full article

Cement slurry is a staple grouting agent, yet its properties can weaken when exposed to heat. Studying grouting materials for use in high-temperature tunnels is therefore a matter of considerable importance. To enhance the applicability of cement-based slurry in high-temperature tunnels, multi-walled carbon nanotubes (MWCNTs), polycarboxylate ether superplasticizer (PCE), and hydroxypropyl methylcellulose (HPMC) were added to improve their performance at elevated temperatures. Various experimental methods were employed to investigate the properties of the modified slurry at different temperatures, including flowability, setting time, compressive strength, and dynamic water retention ratio. Additionally, X-ray diffraction (XRD), thermogravimetric analysis (TG), and scanning electron microscopy (SEM) were used to study the effects of temperature on hardened slurry. Experimental results indicate that the optimal MWCNTs content is 0.32%. At this content, the compressive strength of the hardened slurry after 28 days of curing at 80 °C increases by approximately 20%, reaching 26.4 MPa. PCE improves the fluidity of the slurry, while HPMC enhances its water dynamic water retention ratio. The optimal proportion was found to be 0.3% PCE and 0.2% HPMC. At this ratio, the fluidity of the slurry increased by about 8%, reaching approximately 17.7 cm; the dynamic water retention ratios of 0.8 m/s and 1.0 m/s improved by approximately 22% and 38%, respectively, achieving 35.8% and 18.1%. Furthermore, multi-walled carbon nanotubes significantly enhance the compressive strength of the hardened slurry primarily by suppressing the formation of ettringite during the later stages of hydration, as well as by providing nucleation sites, encapsulating hydration products, and bridging hydration product clusters within the microstructure. This investigation lays a theoretical groundwork for formulating and choosing grouting materials suited to high-temperature tunnel environments. Full article

Octopus maya is a fast-growing species from the Yucatán Peninsula with high economic relevance, accounting for a major share of regional fishery production. However, a significant fraction of the organism, rich in type I collagen, is discarded as by-products, representing a promising and underutilized source for sustainable biomaterials. This study evaluated, through a 3² factorial design, the effect of two factors on the rheological and dynamic mechanical properties of film-forming solutions (FFS). The first factor was the type of food-grade polysaccharide: chitosan (Ch), hydroxypropyl methylcellulose (HPMC), or starch (S). The second factor was the proportion of each polysaccharide blended with ultrasound-extracted Octopus maya insoluble collagen (CIPM), using polysaccharide ratios of 30:70, 50:50, and 70:30 (w/w). This approach aims to valorize octopus by-products through the recovery and functional utilization of collagen. Rheological properties were determined by rotational and oscillatory rheometry at 25 °C, with flow curves fitted to the Carreau-Yasuda model. All formulations exhibited pseudoplastic behavior (n < 1), with viscosity decreasing as shear rate increased. Pure CIPM showed high viscosity (190.36 Pa·s at 1 s⁻¹), which decreased (0.3–10.44 Pa·s) in HPMC and chitosan systems, suggesting their potential suitability for applications requiring fluidity, such as spray coatings or film-forming solutions, based on their rheological properties. In contrast, starch-based systems exhibited higher viscosities (33.54–197.53 Pa·s) and a more structured viscoelastic profile (G′ > G″), suggesting potential suitability for thick coatings or gels requiring structural stability, although these applications were not experimentally validated. These results demonstrate that CIPM-polysaccharide systems enable tunable rheological properties, supporting the use of Octopus maya collagen as a sustainable functional material for advanced food and biomaterial design. Full article

Idelalisib (IDE) is a marketed chiral anticancer drug administered as the S-enantiomer, requiring sensitive monitoring of the R-enantiomer to ensure enantiomeric purity. However, no dedicated capillary electrophoresis (CE) method has been reported for trace-level quantification of R-IDE. In this study, a cyclodextrin-mediated CE method was developed for reliable detection of the R-enantiomer at the 0.1% level (LOD 2 µg/mL; LOQ 5 µg/mL). Systematic screening identified hydroxypropyl-β-cyclodextrin (HP-β-CD) with an intermediate degree of substitution (DS~6.8) as the optimal chiral selector, providing efficient enantioseparation (R_s up to 4.3). The method was validated according to ICH Q2(R2) guidelines, demonstrating suitable precision, accuracy, and robustness. Complementary NMR studies revealed hindered rotation of the 3-phenyl moiety and elucidated the molecular basis of enantioselectivity. Complexation with β-CD and HP-β-CD produced clear diastereomeric differentiation in both ¹H and ¹⁹F NMR spectra, while the simplified ¹⁹F NMR profiles enabled direct enantiomer discrimination. NOESY and ROESY experiments demonstrated distinct inclusion modes, with HP-β-CD accommodating both the fluorinated aromatic ring and the 3-phenyl moiety. These interactions may account for the superior enantioseparation observed with HP-β-CD of intermediate DS. Our validated CE method addresses the distomer determination while NMR insights provide mechanistic understanding of the chiral recognition. Full article

A KGM/CMC/PVA film loaded with a hydroxypropy-β-cyclodextrin/hesperetin (HP-β-CD/HES) inclusion complex was developed for strawberry preservation. The inclusion complex showed an encapsulation efficiency of 70.41 ± 4.01%. Loading the inclusion complex enhanced the barrier and bioactive properties of the films. At the better loading level (KCP-HH3, 1.5%), the film provided nearly complete UV shielding at 200–350 nm and showed a transmittance of approximately 21% at 800 nm. Relative to KCP, KCP-HH3 exhibited lower water vapor permeability (0.69 ± 0.06 g·mm/(m²·h·kPa)) and oxygen permeability (0.066 ± 0.006 g·mm/(m²·h·kPa)). The cumulative HES release from KCP-HH3 reached 82.43 ± 2.19% after 7 days at 98% relative humidity. KCP-HH3 scavenged 78.19 ± 3.71% of DPPH radicals and 88.89 ± 4.30% of ABTS radicals. It also inhibited Escherichia coli (91.18 ± 2.99%), Staphylococcus aureus (79.21 ± 3.45%), and Aspergillus niger (92.85 ± 2.75%). This highest-loading formulation delivered the best overall strawberry-preservation performance. After 12 days of storage, strawberries packaged with KCP-HH3 showed higher firmness (0.89 ± 0.04 N) and total soluble solids (7.96 ± 0.21%), as well as lower weight loss (14.30 ± 0.40%), than the polyethylene control, which showed a firmness of 0.42 ± 0.05 N, total soluble solids of 6.22 ± 0.20%, and weight loss of 16.36 ± 0.66%. These results support the potential of HP-β-CD/HES-loaded KCP films as biodegradable active packaging for fruit preservation. Full article

Background: Static (at-rest) and dynamic (expression-linked) wrinkles are complementary hallmarks of facial aging. While static wrinkles are widely studied, the objective quantification of dynamic wrinkles during active facial movement remains a novel and underexplored frontier. Quantifying both phenotypes under real-life product use requires objective, non-invasive endpoints alongside standardized clinical grading. Aim: This study aimed to evaluate the clinical and instrumental efficacy of a multi-active topical cream on static and dynamic wrinkles over 8 weeks of twice-a-day use. Methods: After a 2-week washout, we conducted a monocentric, open-label study on 62 Chinese women (25–55) who used the topical cream twice daily for 8 weeks (per-protocol n = 49; dynamic-wrinkle subset n = 41; dermatologist 0–9 grading at T0/Timm/W4/W8). The instrumental endpoints were PRIMOS-CR wrinkle morphometry (forehead, crow’s feet) and periocular high-frequency ultrasound (UC22). Dynamic wrinkles were assessed via high-speed smile imaging (max P10; mean P1–P10). Statistics comprised Wilcoxon’s tests for dermatologist-graded (ordinal) endpoints and repeated-measures ANOVA with Dunnett’s tests for continuous instrumental endpoints (α = 0.05). Results: Improvements were evident at Timm (periorbital elasticity −17.70%, global-face elasticity −15.23%, firmness −19.47%, smoothness −20.16%, radiance −25.75%; all p < 0.001). By Week 8, dermatologist-graded wrinkles generally decreased: crow’s feet −26.89%, under-eye −33.74%, glabellar −35.30%, forehead −34.69% (all p < 0.001). PRIMOS showed reductions in wrinkle area/length (forehead area −8.69%, length −12.05%; crow’s feet area −8.70%, length −16.03%; all p < 0.001). Ultrasound indicated increased periocular epidermal thickness (+26.57%) and density (+12.69%) (both p = 0.005). Dynamic-wrinkle grades improved during smiling (under-eye: max −12.64%, mean −15.74%; crow’s feet: max −15.97%, mean −16.89%; all p < 0.001), with reductions across P1–P10. Conclusions: In real-life, with twice-daily use, the multi-active cream demonstrated significant within-subject improvements in both static and dynamic (expression-linked) wrinkles, as supported by dermatologist grading, PRIMOS 3D wrinkle morphometry, and periocular high-frequency ultrasound. Full article

Background/Objectives: α-lipoic acid (ALA) shows therapeutic potential but faces poor aqueous solubility (BCS Class II), gastric instability, and low oral bioavailability (~30%). This work investigated the formulation of cyclodextrin (CD) inclusion complexes of ALA to overcome the aforementioned limitations and improve nutraceutical applications. Methods: Phase solubility studies in simulated gastric and intestinal fluids screened for optimal CD, followed by molecular dynamics simulations and MM-PBSA binding free energy calculations. Inclusion complexes of choice were prepared by grinding, spray-drying, and lyophilization, followed by solid-state characterization (DSC/XRPD/FTIR). Further analysis was performed using pH-shift dissolution (USP II), permeability (PermeaPad^®, Caco-2), and (photo)stability according to ICH. Results: Hydroxypropyl-β-cyclodextrin (HPβCD) emerged as the optimal host due to favorable complexation, as confirmed by phase solubility studies and supported by molecular modeling, which revealed a favorable balance between inclusion complex stability and pH-triggered drug release. Formulations based on spray-dried and lyophilized HPβCD–ALA complexes (HPβALA-sd and HPβALA-lyo), in which ALA was fully amorphized, achieved near-complete dissolution within five minutes under biorelevant pH-shift conditions. This performance markedly exceeded that of free ALA (approximately 66% dissolution at pH 7.4) while maintaining moderate permeability (Papp 8–9 × 10⁻⁶ cm/s). Storage stability was enhanced markedly (88–90% ALA retention after 6 months at 40 °C/75% RH vs. 36% for free ALA) while UV stability was not improved through CD-complexation, probably due to interaction of UV-VIS light with the exposed portion of ALA. Conclusions: Even though the permeability of ALA–CD inclusion complexes remained medium (Papp ~ 8–9 × 10⁻⁶ cm/s) and unaffected by complexation, a significantly improved dissolution profile indicates better expected bioavailability compared to pure ALA. Full article

To enhance the performance of microencapsulated phase change material (MPCM) mortar, hydroxypropyl methyl cellulose (HPMC) was incorporated. This study tested the mortar’s consistency, water retention, water absorption, compressive strength, and thermal conductivity under varying contents of MPCM (as an equivalent volume replacement of sand) and mass contents of HPMC. The results indicate that increasing both MPCM and HPMC contents reduces mortar consistency. Specifically, when HPMC content is 0.05%, 0.10%, and 0.15%, the mortar’s consistency decreases by approximately 24.38%, 35.34%, and 41.30%, respectively, in MPCM-free mortar, with a maximum combined reduction of 74% observed in the 0.15% HPMC and 4% MPCM formulation. MPCM shows a negligible effect on water retention, while HPMC positively influences this property, though not significantly. In contrast, HPMC has little impact on water absorption, whereas MPCM significantly increases it: as MPCM content rises from 0% to 1%, 2%, 3%, and 4%, the mortar’s water absorption increases by 22.55%, 58.82%, 121.57%, and 200.00%, respectively. Both HPMC and MPCM additions lead to reductions in the mortar’s compressive and bond strengths. Notably, a 0.10% HPMC content decreases thermal conductivity by approximately 12% compared to mortar without HPMC. Using the corresponding fitting formulas, predictive values for various performance indicators can be accurately derived. Full article

Resveratrol (RSV) is a poorly water-soluble polyphenolic compound with various potential health benefits, but its pharmaceutical application is limited by low aqueous solubility and poor oral bioavailability. Additive manufacturing (AM), particularly fused deposition modeling (FDM) 3D printing, offers a flexible approach for fabricating oral dosage forms with customized geometry and internal architecture. In this study, hot-melt extrusion (HME) combined with fused deposition modeling (FDM) 3D printing was used to prepare RSV-loaded tablets with different infill patterns. Hydroxypropyl methylcellulose acetate succinate and hydroxypropyl cellulose were selected as polymeric carriers to prepare RSV-loaded filaments suitable for FDM printing. The effects of infill pattern on the solid-state characteristics, dimensional accuracy, mechanical properties, floating behavior, and in vitro drug release of the printed tablets were systematically investigated. Differential scanning calorimetry, powder X-ray diffraction, and polarized light microscopy indicated that RSV was mainly converted into an amorphous or molecularly dispersed state after HME and FDM processing. All designed tablets were successfully printed and showed acceptable shape fidelity, while different infill patterns resulted in variations in tablet weight, mechanical strength, floating duration, and release behavior. In vitro dissolution studies showed that the RSV release profiles were dependent on the internal infill architecture. Tablets with more complex infill patterns generally exhibited slower drug release, which may be related to differences in internal pore structure, medium penetration pathways, matrix hydration, and diffusion distance. Release kinetic analysis further suggested that RSV release from the printed tablets involved a combination of diffusion and polymer relaxation processes. These results demonstrate that infill pattern is an important structural parameter for modulating the mechanical performance and drug release behavior of FDM 3D-printed RSV tablets. This study provides useful guidance for the design of 3D-printed oral dosage forms with tunable release characteristics. Full article

A time-saving approach to gelatin-based hydrogels with versatile properties is highly desirable. Herein, we report the rapid fabrication of new gelatin-containing hydrogels with favorable mechanical properties, biocompatibility and antibacterial capability. Frontal polymerization (FP) of acrylic acid (AA), acrylamide (AM), hydroxypropyl acrylate (HPA) with gelatin methacryloyl (GelMA) enables the rapid formation of multifunctional hydrogels within 7 min, providing a highly efficient route for gelatin-based hydrogel fabrication. The effect of GelMA content on FP features and hydrogel properties was systematically investigated. The resultant hydrogels show attractive collective properties with tensile strength up to 101.3 kPa, elongation at break up to 227.7%, cell viability of 96% after 24 h, and antibacterial activity against S. aureus (92.2%). In addition, the FP of the hydrogels with use of forsythia-derived carbon dots (F-CDs) as bioactive nanofillers is explored, conferring the hydrogels with enhanced mechanical performance and biocompatibility, demonstrating the applicability of this FP strategy upon incorporating functional additives. This work provides a simple and effective approach for the rapid preparation of gelatin-containing hydrogels with versatile functions promising for biomedical applications such as wound healing and tissue engineering. Full article

Background: Thymoquinone (TQ), a bioactive compound derived from Nigella sativa L., exhibits promising antioxidant, anti-inflammatory, and wound-healing properties; however, its clinical application is limited by poor solubility and instability. Methods: In this study, three electrospun nanofiber systems based on different polymeric matrices, PVP (N1), PVP/HPβCD (N2), and PVP/PCL (N3), were developed as potential wound dressing materials for controlled TQ delivery. Results: All formulations produced uniform nanofibrous structures with TQ molecularly dispersed within the polymer matrix, as confirmed by SEM, XRPD, and FTIR analyses. The composition of the nanofibers significantly influenced their physicochemical and functional properties. The N2 system, containing hydroxypropyl-β-cyclodextrin (HPβCD), exhibited the smallest fiber diameter (~208 nm), the fastest drug release, and enhanced antioxidant and anti-inflammatory activity due to improved TQ solubility. In contrast, the N3 system, incorporating polycaprolactone (PCL), formed thicker fibers (~1089 nm) and demonstrated sustained release behavior, the highest mucoadhesion, and the most pronounced wound-healing effect (90% closure after 24 h). Stability studies revealed that HPβCD significantly improved TQ resistance to thermal, humidity, and photolytic degradation, whereas the PVP-based system without stabilizers showed the lowest stability. Principal component analysis (PCA) confirmed that nanofiber performance is governed by two key factors: drug availability and sustained release combined with bioadhesion. Importantly, wound-healing efficiency correlated more strongly with the latter. Conclusions: The results demonstrate that rational design of polymer composition enables modulation of TQ delivery and biological response. Among the tested systems, PVP/PCL nanofibers appear to be the most promising candidates for wound-dressing applications due to their ability to provide sustained drug release and enhance tissue regeneration. Full article