Search Results (705)

Background/Objectives: The recent advances in pulmonary delivery have shifted the paradigm to the development of inhalable drug-loaded polysaccharide particles that can be positioned at the respiratory interface while reducing the systemic exposure. Quercetin has broad anticancer activity but remains difficult to translate because of its poor aqueous solubility, limited bioavailability and rapid metabolic loss. Here, we report quercetin-loaded chitosan/Salvia hispanica polysaccharide nanoparticles as a natural polyelectrolyte nanocarrier for pulmonary delivery in lung cancer. Methods: Central composite design (CCD) and artificial neural network (ANN) models were used for mapping the factors to responses. Results: The models displayed a higher predictive accuracy and optimization reliability for identifying the optimized formulation. The optimized nanoparticles showed a quasi-spherical morphology (mean hydrodynamic diameter = 331 ± 14.34 nm) with cationic ζ-potential of +36.3 ± 2.56 mV and polydispersity index of 0.15. The optimized formulation showed acceptable powder-flow characteristics, an encapsulation efficiency of 73.8 ± 0.73%, drug loading of 14.20 ± 0.22%, and biphasic release with sustained quercetin release over 48 h. In A549 and H460 cell lines, nanoencapsulation increased the antiproliferative effect of quercetin relative to the free compound, yielding lower IC₅₀ values after 48 h of exposure. The nanoparticles showed greater suppression of wound closure, increased reactive oxygen species fluorescence and clear cellular uptake. Blank nanoparticles produced only limited effects. Conclusions: These results indicate that CCD/ANN-guided chitosan/Salvia hispanica polysaccharide nanoparticles provide a promising nanodelivery tool for quercetin delivery and enhanced in vitro activity in lung cancer cells, while the observed aerosol performance advocates further investigation of their pulmonary delivery potential. Full article

Backgorund/Objectives: Respiratory diseases represent a substantial global health burden and require effective localised pulmonary delivery strategies, particularly for poorly water-soluble therapeutic molecules. Nanoparticle-based drug delivery systems, especially those manufactured using microfluidics, have emerged as promising approaches to overcome pulmonary barriers, enhance local drug retention, and reduce systemic side effects. Among these nanocarriers, solid lipid nanoparticles (SLNs) and solid hybrid nanoparticles (SHNs) combine biocompatibility with controlled release and improved formulation stability. Methods: In this study, SLNs and lipid–chitosan SHNs were developed using microfluidic technology as candidate platforms for pulmonary drug delivery, with Cyclosporine A (CyA) used as a model hydrophobic cyclic peptide. Nanocarriers were produced using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol as lipids, with low-molecular-weight chitosan incorporated to obtain hybrid systems. Physicochemical properties were evaluated using dynamic light scattering (DLS) and ζ potential measurements, while morphology and structural organisation were investigated using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Results: The microfluidic approach enabled the production of nanoparticles with controlled sizes below 200 nm, narrow size distributions, and good reproducibility. In addition, the SHNs exhibited a positive surface charge, high encapsulation efficiency (~80%), and good colloidal and thermal stability. In vitro release studies showed an initial burst release followed by sustained CyA release, reaching approximately 94% cumulative release within 6 h. The Korsmeyer–Peppas model was used as the standard kinetic model. No blank nanoparticles were used as controls in the EE and release assay. Conclusions: Overall, these findings support further investigation of microfluidic-produced lipid and hybrid nanoparticles as candidate platforms for pulmonary drug delivery. Full article

In the present work, we investigated the role of polydopamine coatings in anchoring TiO₂ P25 nanoparticles on gold and ITO surfaces. For this purpose, we studied the adhesion of polydopamine-coated aggregates of TiO₂ nanoparticles on bare substrates and of aggregates of bare TiO₂ nanoparticles on polydopamine-coated substrates. Coating with polydopamine was accomplished by oxidation in air of alkaline aqueous dopamine solutions in which the nanoparticles or the substrates were immersed. Dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy were used for the chemical and morphological characterization of aggregates of the nanoparticles. The adhesion of aggregates of the nanoparticles on the substrates was evaluated by means of AFM and XPS. The results of this study suggest that the adhesion of TiO₂ P25 nanoparticles on polydopamine films, as well as of polydopamine-coated TiO₂ P25 nanoparticles, is a balance of several contributions: chemical interactions, electrostatic interactions, and coating roughness. Electrostatic attraction and repulsion between nanoparticles and the substrate appear to play an important role, as indicated by the ζ-potential values of nanoparticles and substrates. Full article

Objectives: The physical stability of concentrated azelaic acid nanosuspensions cannot be predicted solely from interfacial stabilisation but reflects the interplay between particle size-dependent thermodynamic driving forces, polymer-mediated rheological structuring and the resulting bulk microstructural organisation. This study employed an A-optimal design of experiments (18 runs) to investigate formulation–process relationships in concentrated azelaic acid nanosuspensions (10–20% w/w) stabilised with a dual HPMC–chitosan system. Methods: Particle size, ζ-potential, rheological behaviour, solid-state properties and in vitro permeation across Strat-M® membranes were evaluated, and formulation–process relationships were analysed using multivariate modelling and logistic regression. Results: Particle size (342–1118 nm; R² = 0.97) was primarily governed by the applied milling regime. Logistic regression demonstrated a size-dependent probability of crystal growth, with the estimated particle-size transition point (predicted probability = 0.5) shifting from approximately 424 nm after preparation to 594 nm following accelerated storage at 40 °C. CHI concentration controlled ζ-potential (+18.5 to +47.9 mV), although ζ-potential alone did not adequately explain the observed storage stability. Where measurable, zero-shear viscosity (68–45,462 mPa·s) reflected substantial differences in low-shear rheological structuring, while formulations containing higher HPMC concentrations generally exhibited improved stability, consistent with polymer-mediated kinetic constraints on crystal growth. In vitro permeation studies using Strat-M^® membranes demonstrated permeation behaviour consistent with structured diffusion-controlled systems, exhibiting lower flux but more uniform permeation profiles than the reference formulation under the applied experimental conditions. Conclusions: Integration of multivariate modelling with rheological, solid-state and permeation characterisation provided an integrated understanding of the formulation–process relationships governing the short-term physical stability and comparative in vitro transport behaviour of concentrated dermal AZA nanosuspensions. Full article

A series of molecularly imprinted polymers (MIPs) based on hydroxypropyl-β-cyclodextrin (HPCD) crosslinked with 1,6-hexamethylene diisocyanate (HMD) or toluene diisocyanate (TDI), as well as hybrid chitosan–HPCD polymers crosslinked with genipin, were synthesized using levofloxacin and fluorescein as template molecules. The structure and spatial organization of the obtained materials were characterized by FTIR spectroscopy, FTIR microscopy mapping, and ζ-potential measurements. The influence of pH, crosslinker content, and template structure on sorption performance was investigated. All MIPs exhibited maximum sorption at pH 3.0. The highest sorption capacity toward levofloxacin was achieved for the LV–Chit–HPCD–Genipin_MIP (74.8 mg/g), whereas the fluorescein-imprinted FL–HPCD–TDI_MIP (1:1) demonstrated the highest sorption capacity (135.5 mg/g) and selectivity coefficient (84.1). Dynamic column experiments confirmed efficient analyte extraction, reducing the analyte concentration by more than 90% after ten loading cycles. All synthesized MIPs exhibited excellent regenerability, with less than 3% loss of sorption efficiency after ten consecutive sorption–desorption cycles. The applicability of the developed sorbents to real matrices was demonstrated using milk and blood plasma samples after minimal sample preparation. Fluorescein extraction efficiencies reached 97.6% and 93.6% for milk and plasma, respectively. The obtained results demonstrate that HPCD-based MIPs combine high sorption capacity, exceptional selectivity, operational stability, and applicability to complex biological matrices, making them promising materials for selective sample preparation, analyte preconcentration, and controlled drug delivery systems. Full article

Immunotherapy can reduce treatment-related side effects but shows limited efficacy in “cold tumors,” whose immunosuppressive tumor immune microenvironment is characterized by abundant M2 macrophages and poor T cell infiltration. Because biopsy-based qualitative assessment of the tumor microenvironment is invasive and conventional imaging lacks functional information, this study aimed to develop an M2 macrophage-targeted theranostic agent enabling non-invasive photoacoustic (PA) imaging and pH-triggered cytotoxicity. A pullulan-based nanogel conjugated with mannose and near-infrared dye (IR-820) was further functionalized with the pH-responsive doxorubicin (DOX) prodrug, Aldoxorubicin, to develop Pullulan-mannose-IR820-Aldoxorubicin (PMID) nanogel. PMID was successfully synthesized, and the resulting self-assembled nanogels (<100 nm) exhibited a highly negative ζ-potential, near-infrared absorption peaks at 780 and 850 nm, and PA contrast comparable to IR-820 at 850 nm excitation. Dialysis studies demonstrated suppressed drug release at neutral pH (~20%) but accelerated release under acidic conditions, reaching ~80% within 48 h at pH 5.5, consistent with hydrazone hydrolysis and supporting tumor/lysosome-activated delivery. In RAW264.7 macrophages, PMID nanogel showed preferential uptake by M2-poralized versus M1-polarized macrophages, outperforming non-mannosylated PID nanogel and IR-820, and produced the strongest PA signal in M2 macrophage pellets. PMID nanogel also induced the highest concentration-dependent cytotoxicity in M2 macrophages, and microscopy indicated lysosomal accumulation of the nanogel with partial nuclear localization of released DOX. These findings support the use of PMID nanogel as M2 macrophage-targeted PA contrast agents and pH-responsive drug carriers with the potential to deplete immunosuppressive macrophages, modulate cold tumor microenvironments, and improve precision cancer theranostics. Full article

Gene delivery with cationic polymers requires balancing DNA compaction, colloidal stability, and intracellular release, yet for imine-linked low-molecular-weight polyethyleneimine (PEI) vectors, quantitative relationships connecting the N/P ratio with the full property–transfection cascade remain undefined. Here, two amphiphilic non-viral vectors were prepared by linking a hydrophobic benzene–siloxane core (TAS) to hyperbranched PEI (800 or 2000 Da) through reversible imine bonds and complexed with DNA across a broad N/P range (10–600). Polyplexes were characterized by atomic force microscopy (AFM), dynamic light scattering (DLS), ζ-potential, agarose gel electrophoresis, transfection via green fluorescent protein (GFP) imaging and luciferase assay in HeLa cells. Both vectors formed spherical nano-entities (AFM diameters ~30 nm for TAS-PEI800; ~100 nm for TAS-PEI2000). TAS-PEI2000 achieved complete DNA retardation at N/P ≈ 30 versus N/P ≈ 150 for TAS-PEI800, consistent with its higher charge density (ζ = +37.59 vs. +18.35 mV). Transfection efficiency was superior for TAS-PEI2000 across most N/P ratios; however, TAS-PEI2000 displayed an optimal transfection efficiency at N/P ≈ 100 (ζ ≈ 3.84 mV), beyond which efficiency declined, indicating a binding–release trade-off. Cell viability remained >77% across the N/P range for TAS-PEI800, but dropped below 25% at N/P ≥ 400 for TAS-PEI2000. A phenomenological logistic model identified characteristic transition thresholds (θ ≈ 60 for TAS-PEI800; θ ≈ 40 for TAS-PEI2000), capturing the onset of cooperative self-assembly; however, the post-optimum decline observed for TAS-PEI2000 requires additional inhibitory terms. These findings demonstrate that PEI molecular weight governs both the N/P threshold required for efficient transfection and the width of the therapeutic window, thereby providing structure–activity descriptors for the rational design of imine-linked polyplex systems. Full article

Background: Despite extensive development of liposomal antibiotics, the structural determinants governing their stability, release, and biological activity remain poorly understood. This study investigated how the cholesterol content and drug-to-lipid ratio affect membrane organization and thereby determine the physicochemical and biological properties of linezolid-loaded liposomes. Methods: Nine liposomal formulations, varying in their cholesterol content (10–30 wt%) and drug-to-lipid ratios (1–5%), were prepared by thin-film hydration. Membrane organization was analyzed by ATR-FTIR spectroscopy and principal component analysis. Liposomes were further characterized by particle size, ζ-potential, encapsulation efficiency, storage stability, in vitro release in phosphate buffer with and without bovine serum albumin, antibacterial activity against B. subtilis, and antimycobacterial activity in an ex vivo PBMC-derived Mycobacterium tuberculosis granuloma model. Results: The cholesterol content and drug-to-lipid ratio markedly altered membrane interfacial organization, particularly the hydration of the carbonyl and phosphate regions. These structural changes correlated with differences in storage stability, protein-responsive release, and antibacterial activity. Functional behavior was non-monotonic, as 30-L showed the highest overall storage stability, while the apparent release depended jointly on the cholesterol content, drug loading, and medium. BSA altered the composition-dependent release pattern instead of producing a uniform effect. In the exploratory granuloma model, the formulations 10-S, 10-L, and 30-M reduced M. tuberculosis CFU by >99%, whereas free linezolid produced approximately 60% inhibition. Conclusions: Membrane interfacial organization is a key determinant of the functional performance of liposomal linezolid, establishing a structure–property–function relationship that provides a mechanistic basis for the rational design of liposomal antibiotic delivery systems for tuberculosis therapy. Full article

Cataracts are the leading cause of reversible blindness worldwide; this condition results from the aggregation of lens proteins. Currently, surgery remains the only treatment; however, there is growing interest in non-surgical approaches, including the use of bioactive compounds incorporated into nanostructured systems designed to enhance solubility, enable controlled release, and improve bioavailability and bioactivity. Among the bioactive compounds investigated, curcumin has attracted considerable attention due to its antioxidant and anti-inflammatory properties, positioning it as a potential anticataractogenic agent. In the present study, curcumin-loaded nanoemulsion was developed via ultrasonication and characterized by average particle size, D90 percentile, ζ potential, and rheological behavior. In addition, its anti-cataract efficacy was evaluated both using an in vivo model in rats and an ex vivo model employing human cataract samples. The resulting curcumin-loaded nanoemulsion exhibited an average particle size of 152 ± 19.79 nm with a monomodal distribution, along with good physical stability over time. The nanoemulsion exhibited apparent viscosity between 30 and 25 mPa·s, at shear rate values (100 to 0 s⁻¹), indicating slight shear-thinning behavior. Regarding the effect on cataracts, in the in vivo model, cataract reversal was observed. Furthermore, ex vivo isothermal titration calorimetry (ITC) analyses indicated exothermic heat exchange between the curcumin nanoemulsions and cataract fragments, consistent with binding interactions occurring within lens components, likely involving crystallin proteins. These findings provide biophysical and in vivo evidence that intravitreally administered curcumin-loaded nanoemulsions not only prevent but actively reverse lens opacity, positioning them as a promising non-surgical therapeutic approach for cataract treatment. Full article

Lasiodiplodia theobromae is an important postharvest fruit rot pathogen that reduces the shelf life and marketability of durian. This study developed an ultrasound-assisted submicron curcumin-removed turmeric oleoresin and chitosan coating and evaluated its antifungal activity against L. theobromae in ‘Ri 6’ durian. An optimum formulation of 250 g L⁻¹ CRTO and 11.18 g L⁻¹ chitosan was obtained using response surface optimisation and prepared with ultrasound energy input of 384 J mL⁻¹. The optimised dispersion showed a hydrodynamic droplet size of 514 nm, a low polydispersity index of 0.16, a positive ζ-potential of +38 mV, and an emulsification efficiency of 86.16%; it retained one of the highest degrees of visual homogeneity among the 15 design formulations after 7 months of storage at 25 °C. In vitro assays showed strong dose-dependent inhibition of L. theobromae, with mycelial growth suppressed by 98.4–100% at 0.10 C₀ and 0.20 C₀; the two concentrations did not differ significantly (p > 0.05). Lesion development on wounded-inoculated fruit was reduced by 84.8–88.6% in CRTO–chitosan-coated fruit compared with the untreated control. Ultrasound-assisted submicron CRTO–chitosan coating is therefore a promising natural strategy for controlling postharvest fruit rot caused by L. theobromae in ‘Ri 6’ durian. The study was limited to one cultivar and one harvest batch, and postharvest quality, sensory attributes, and long-term dispersion stability were not assessed. Full article

Soybean dregs, one of the main byproducts of traditional soybean processing, are rich in insoluble dietary fiber (IDF), which possesses high mechanical strength and thermal stability. After surface reconstruction treatment, they have the potential to serve as a Pickering emulsion stabilizer, as these properties enable the particles to maintain their structural integrity at the oil–water interface. In this research, high-purity soybean dreg insoluble dietary fibers (HPSIDFs) were modified by alkaline H₂O₂, with oleic acid (OA) modified in a green synergistic modification. The surface of HPSIDF was etched to increase the reaction sites for subsequent hydrophobic modification, which enhanced the emulsification properties. Finally, the performance of the particles in Pickering emulsions and the emulsification mechanism were analyzed. The absolute value of the ζ-potential of the hydrophobically modified high-purity soybean dreg insoluble dietary fiber (O-HPSIDF) increased from 15.87 mV to 37.27 mV. The stability of the Pickering emulsion stabilized by O-HPSIDF was greatly enhanced; the droplet size of the emulsion decreased; the distribution was more uniform. The emulsifier particles formed a network structure at the interface, which imparted considerable mechanical strength to the emulsion, as evidenced by the increased storage modulus and viscosity. Full article

This study systematically investigates the effects of Ni and Al addition to a zinc bath on the microstructure, corrosion resistance and Vickers hardness of hot–dip galvanized coatings on Q235 steel. The Zn, Zn–0.04 wt.% Ni and Zn–0.04 wt.% Ni–1 wt.% Al coatings are characterized by scanning electron microscopy (SEM), X–ray diffraction (XRD), neutral salt spray (NSS) testing, electrochemical measurements and Vickers hardness testing. The addition of Ni refines and thins the ζ phase, increases the thickness of the δ phase, reduces the total coating thickness to 56.33 ± 0.89 μm and improves the corrosion resistance. With further Al addition, a continuous and dense inhibition layer forms at the interface, and the coating consists solely of this inhibition layer and the η phase; the total thickness is drastically reduced to 17.66 ± 1.78 μm, accompanied by a substantial improvement in both corrosion resistance and hardness. Electrochemical analysis reveals that the Zn–0.04 wt.% Ni–1 wt.% Al coating exhibits the most negative corrosion potential (0.61 V) and the smallest corrosion current density (2.07 μA·cm⁻²). Characterization of the corrosion products reveals that Al helps to stabilize Zn₅(OH)₈Cl₂·H₂O and Zn₅(OH)₆(CO₃)₂, thereby enhancing the corrosion resistance of the coating. Full article

To survive, cells are able to adapt to a wide range of adverse conditions, such as varying pH from optimal (~7.4). They do this through mechanisms including acid-sensing ion channels, which alter cytosolic ion content and thus the cell’s electrophysiological profile. However, the impact of this adaptation on cellular electrophysiology remains unexplored. We investigated the effects of culture at a range of extracellular pH on the electrophysiological features of breast cancer cell lines MDA-MB-231 and MCF-7. Cells were subject to an acid–neutral–base pH from 3.0 to 9.2, after which their membrane potential (V_m), cytoplasm conductivity σ_cyto, effective membrane conductance G_eff, and ζ-potential were measured. Cells were also analyzed after permeabilization, to examine whether observed changes were due to cell surface chemistry, or to V_m. Both cell lines exhibited different electrophysiological phenotypes in acidic environments (pH < 6.7); MDA-MB-231 exhibited statistically significant differences in ζ-potential, V_m, G_eff and σ_cyto; MCF-7 only exhibited significant differences in σ_cyto. These findings suggest cells adapt to acidic microenvironments by altering V_m and potentially ζ-potential, reducing the extracellular potential, and hence potentially lowering proton concentration at the extracellular membrane surface. This offers new insights into potential therapeutic avenues to target the pH-dependent adaptations of cancer cells. Full article

Developing sustainable lithium-ion batteries (LIBs) requires binder–carbon interfaces that combine mechanical compatibility, interfacial cohesion, and reduced environmental impact. In this work, density functional theory calculations were used to evaluate the interactions of representative binder monomers acrylonitrile (AN), pyrrole (PY), vinylidene fluoride (VDF), and tetrafluoroethylene (TFE) with pristine graphene and chitosan-functionalized graphene oxide (GO/chitosan). Structural, energetic, electronic, and topological features were analyzed using counterpoise-corrected interaction energies, frontier-orbital descriptors, molecular electrostatic potential maps, projected density of states, noncovalent interaction analysis, and quantum theory of atoms in molecules topology. Final interaction energies were obtained at the M06-2X/def2-TZVP level with Boys–Bernardi counterpoise correction to provide a more robust description of weak noncovalent adsorption. Most binder–surface interactions fall within a weak, near-thermoneutral adsorption regime. On pristine graphene, AN and PY exhibit weakly favorable adsorption, with minimum counterpoise-corrected interaction energies of −3.13 and −2.10 kcal mol⁻¹, respectively, whereas TFE and VDF show orientation-dependent, near-neutral behavior. GO/chitosan introduces oxygen-containing and amino functionalities that modify the adsorption balance, particularly for selected perpendicular configurations of fluorinated monomers, although the net stabilization remains modest. NCI, QTAIM, MEP, and PDOS analyses indicate that surface functionalization increases the chemical heterogeneity and directionality of local contacts; however, these local descriptors do not necessarily translate into strong global adsorption energies. Overall, the results identify GO/chitosan as a chemically tunable interface for binder–carbon compatibility in LIB electrodes and demonstrate the importance of triple-ζ, counterpoise-corrected calculations for evaluating weak binder–surface interactions. Full article

High-risk neuroblastoma (HR-NB) remains a major clinical challenge due to the emergence of therapy resistance. In this study, the anticancer effects of seven previously synthesized betulin (BET), betulinic acid (BA) and ursolic acid (UA) derivatives (1–7) and of their natural precursors BET, BA and UA (8–10) were investigated in HTLA NB cells, selected as the experimental model by MTT assay, to find a possible solution to drugs that have lost their effect. Dynamic light scattering (DLS) analysis showed that amphiphilic compounds 1 and 4–7 form nanovesicles (240–448 nm) in water, while all compounds have high positive ζ-potential (ζ-p, +28.5–+83.1 mV), supporting favourable membrane interaction and cellular uptake. Cytotoxic experiment results and related IC₅₀ values were expressed as the mean ± SD of four independent experiments run in triplicate. Most derivatives exhibited a cytotoxic activity higher than that of their natural precursors and outperformed etoposide; they were particularly effective against the multidrug resistant (MDR) HTLA ER cells. Among them, the ursolic acid (UA) derivative 7 emerged as the most active compound, displaying sub-micromolar to low micromolar IC₅₀ values and markedly improving the activity of native UA. Functional studies revealed that it induces complete suppression of clonogenic growth at low micromolar concentrations in both HTLA ER and parental HTLA 230 NB cells. In addition, a concentration-dependent downregulation of Akt, p-Akt, BMI1 and PARP, was observed consistently with a marked suppression of survival pathways and loss of cellular homeostasis. Collectively, our experiments, which need further direct investigation to confirm subsequent assumption, could suggest that compound 7 could kill cancer cells via a non-apoptotic, bioenergetic collapse mechanism. All of these findings suggest compound 7 as a promising mitochondria-targeted lead candidate and support amphiphilic triterpenoid derivatives as attractive platforms for overcoming multidrug resistance in high-risk NB. Full article