Search Results (5,448)

Small-molecule hydrogels have gradually become a research hotspot compared with polymeric hydrogels, but their practical advantages have not been fully realized in the development of pharmaceutical formulations. This study aimed to explore whether the N-methyl-D-glucosamine (GLU) could be introduced to form a ibuprofen (IBU) hydrogel for overcoming its water solubility defect and optimizing its pharmaceutical properties. Such an IBU-GLU hydrogel was prepared by simply mixing IBU with GLU in small-volume deionized water. The formed IBU-GLU hydrogel was characterized by SEM, rheology, DSC, PXRD and FTIR analyses. In addition, the solubility, in vitro release and permeability were also investigated to evaluate the solubilization and permeability-promoting effects. The resulting IBU-GLU hydrogel exhibited a typical 3D structure with excellent viscoelasticity, which relied on the equilibrium of aggregation and dissolution, as well as a good miscibility between IBU and GLU, and self-assembly driven by intermolecular interactions in an aqueous environment. Compared to pure IBU, the IBU solubility of the IBU-GLU hydrogel was significantly improved by 38.4-fold. Furthermore, IBU-GLU hydrogel demonstrated superior release rates and supersaturation ability, which was attributed to its high-energy state and internal molecular complexation. Additionally, compared with the commercially available IBU hydrogel, the prepared IBU-GLU hydrogel significantly accelerated IBU membrane permeation. Thus, this study highlighted that the designed IBU-GLU hydrogel could serve as a feasible approach to enhance the release and permeability of IBU for its druggability optimization. Full article

Alkaline water electrolysis (ALK) is essential for renewable energy integration, yet traditional models using a fixed minimum operating power often overestimate low-load flexibility by neglecting state-dependent safety boundaries. This study develops an electro-thermal-mass multiphysics dynamic model that treats the transient hydrogen content in oxygen (H₂-in-O₂) concentration as a first-principles state variable. Based on a quasi-steady-state safety balance, a dynamic minimum operating power constraint is derived to replace empirical static limits. A key feature of this model is the explicit coupling of Arrhenius thermal diffusion and pressure-differential-driven permeation during load transients, allowing the safety threshold to respond to real-time system states. Year-round simulations of a 30 MW industrial system under a wind–solar time series reveal that thermal inertia, with a time constant of approximately 4.2 h, induces a sustained mismatch between low-power operation and high system temperature. Under high-temperature and rapid-ramp conditions, the dynamic safety lower bound reaches 28.2% of the rated capacity, exceeding the conventional 20% static threshold by 8.2 percentage points. This deviation results in 378.3 MWh of implicit curtailment and 60.5 h of additional downtime annually, leading to a green hydrogen production deficit of approximately 42.2 t/year. This research provides a theoretical foundation and technical reference for the optimal control and flexibility assessment of industrial-scale green hydrogen systems under fluctuating power supply conditions. Full article

While bacterial skin infections are highly prevalent worldwide, their eradication with conventional topical medications remains highly challenging. Cinnamic acid (CA) is a naturally occurring molecule with interesting antibacterial properties, but its efficacy is hindered by poor aqueous solubility and skin permeability. To overcome these challenges, CA was encapsulated within novasomes, which are multilamellar vesicles composed of fatty acids, cholesterol, and nonionic surfactants. The novasomes were optimized using a 2³ factorial design and the optimized formulation was incorporated in a carbopol gel base and evaluated for spreadability, rheological properties, drug release, ex vivo skin permeation and deposition, and antibacterial efficacy. The optimized novasomes featured desirable properties, including high drug entrapment (94.75 ± 0.05%), nanometric particle size (123.80 ± 1.44 nm), and negative zeta potential (−36.63 ± 0.61 mV). CA novasomal gel exhibited shear-thinning behavior, coupled with thixotropic properties. It also achieved approximately 1.7-fold higher flux through rat skin compared with the free CA gel. Moreover, the novasomes showed a two-fold reduction in the minimum inhibitory concentration of the drug against E. coli compared with the drug suspension. These findings support the potential of CA novasomal gel to enhance its antibacterial activity and skin permeability, making it a promising approach for topical delivery of this naturally occurring compound. Full article

Background/Objectives: Antibiotics are commonly used for acne treatment. However, increasing bacterial resistance has prompted interest in natural antimicrobial agents, such as thymol (THY), as alternative therapies. This study investigated the effectiveness of Leciplex cationic nanovesicles encapsulating thymol (LPX-THY) as a promising topical acne management strategy. Methods: Leciplex nanovesicles were assembled using soy phosphatidylcholine (SPC) and cationic surfactants and characterized in terms of particle size, zeta potential, entrapment efficiency, morphology, in vitro release, and ex vivo skin permeation. The optimized formulation was subsequently incorporated into Carbopol/HPMC gel base and evaluated in terms of viscosity, in vitro release, ex vivo skin permeation, in vitro antimicrobial study, and in vivo assessment in a rat model. Results: Optimal THY-LPX nanovesicles made of SPC and Dimethyldidodecylammonium bromide DDAB in a 1:1 molar ratio showed circular outline with particle size, zeta potential, and entrapment efficiency of 187.7 ± 1.78 nm, 36.97 ±0.21 mV, and 60.5 ± 2.3%, respectively. THY-LPX gel demonstrated minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) at a concentration of 156.25 µg·mL⁻¹ against Staphylococcus aureus, a clear absence of biofilm coating under SEM, and substantial red fluorescence, indicating reduction in viable bacteria under a confocal laser microscope. In vivo study showed enhanced anti-inflammatory effect evidenced by substantial ear skin thickness reduction; 72.7% for THY-LPX gel-treated rats compared to 41.7% and 20% for THY gel and blank LPX gel-treated groups, respectively. Histopathological investigation further confirmed reduced inflammatory response in rats treated with optimized THY-LPX gel. Conclusions: The developed THY-LPX gel serves as a potential topical delivery platform of THY for acne therapy. Full article

The effect of reversible addition–fragmentation chain transfer (RAFT) polymerization on the structure, morphology, and thermal degradation behavior of polypropylene glycol maleate–acrylic acid copolymers (p-PGM:AA) was investigated using 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) as the RAFT agent. Copolymers synthesized at different CPDT concentrations were characterized by ¹H/¹³C NMR spectroscopy, gel permeation chromatography (GPC), transmission electron microscopy (TEM), thermogravimetric analysis coupled with mass spectrometry (TG–MS), isoconversional kinetic methods, and density functional theory (DFT) calculations. ¹H NMR spectroscopy revealed a progressive decrease in the relative intensity of vinyl proton signals with increasing CPDT concentration, indicating enhanced conversion of unsaturated fragments during copolymerization. Alkaline hydrolysis followed by ¹H NMR and GPC analysis of the degradation products confirmed cleavage of polyester segments and yielded low-molecular-weight fragments with M_n = 1370 g mol⁻¹ and narrow dispersity (Đ = 1.035), providing additional information on the architecture of the vinyl-polymerized segments. Increasing CPDT concentration resulted in lower molecular weights and narrower molecular weight distributions of the soluble copolymer fractions. TEM analysis demonstrated broader domain size distributions and increased morphological heterogeneity in RAFT-modified samples, accompanied by an increase in swelling degree. Thermogravimetric analysis showed that RAFT-modified systems undergo multi-stage thermal degradation with the appearance of an additional low-temperature stage associated with thermolabile fragments. TG–MS revealed earlier evolution of CO₂ and oxygen-containing species and changes in the distribution of volatile products. DFT calculations indicated a decrease in the HOMO–LUMO energy gap and suggested the participation of RAFT-derived fragments in the energetic characteristics of decarboxylation processes. Isoconversional and nonlinear kinetic analyses demonstrated increased kinetic heterogeneity for branched copolymer s synthesized at elevated CPDT concentrations, whereas cross-linked systems exhibited more uniform degradation behavior. The combined experimental and theoretical results demonstrate that RAFT polymerization provides an effective route for tuning the macromolecular architecture, morphology, and thermal degradation pathways of p-PGM:AA copolymers. Full article

Although coconut water is recognized for its desirable sensory appeal and nutritional composition, its broader industrial use is constrained by the rapid deterioration that occurs after extraction. In this study, crossflow microfiltration of coconut water with a silicon carbide membrane was optimized by investigating pressure and temperature through a face-centered design (FCD) and artificial neural network modeling coupled with a genetic algorithm (ANN–GA). Permeate flux and fouling index were used as process responses, and the optimized condition was further examined in terms of hydraulic resistance, fouling behavior, and retention of minerals and primary metabolites. Pressure and temperature affected the process differently: permeate flux showed marked nonlinear behavior, whereas fouling index was governed mainly by pressure. At the sample level, ANN described permeate flux more accurately than FCD (R² = 0.99 vs. 0.96), whereas FCD showed better grouped cross-validated predictivity across unseen pressure–temperature conditions (Q² = 0.85 vs. 0.57). For the fouling index, FCD outperformed ANN in both sample-level fit and grouped validation (R² = 0.95 vs. 0.60; Q² = 0.70 vs. 0.61). Both approaches converged on the same favorable operating window, and experimental validation at 60 kPa and 35 °C yielded 1085.23 ± 23.12 L h⁻¹ m⁻² and 83.56 ± 1.56%. During concentration mode, flux decline was severe but predominantly reversible, with high clean-water permeance recovery after chemical cleaning. Resistance partition and fouling modeling indicated that the main hydraulic limitation was associated with concentration polarization and external cake-layer buildup rather than irreversible membrane damage. The clarified fraction also preserved high transmission of major minerals and relevant primary metabolites, indicating that the selected condition combined high productivity, manageable fouling, and satisfactory nutritional retention. Full article

Refractory metals are being studied as alternatives to Pd and its alloys for the separation of hydrogen in high-temperature processes. The development of a membrane reactor for the production of hydrogen via water splitting has required studying hydrogen permeability through Ta at temperatures above 1273 K, for which no data is available in the literature. A dedicated experimental setup has been realized for testing Ta tubes in the temperature range 673–1573 K. Despite the use of controlled atmospheres and ultra-pure gases (with oxygen content below a few ppm), the tests over 1473 K have involved the formation of oxide layers over the metal surfaces, as verified by SEM-EDS analyses. The presence of oxide layers significantly increases the energy barrier to permeation: in agreement with a modest surface oxidation, at lower temperatures (673–1273 K) the activation energy of 2679.8 K has been measured against the value of 30,691 K measured in the high-temperature tests (1473–1573 K). Full article

Simple and non-invasive transdermal vaccination is an attractive alternative to conventional injection-based immunization. However, the effectiveness of transdermal vaccines is often constrained by the stratum corneum barrier. Although the use of solid-in-oil (S/O) nanodispersion technology has successfully facilitated skin permeation to induce an immunological response, the antibody titers remain suboptimal. Herein, a dectin-1 selective ligand, laminarin, was used as an immunostimulatory adjuvant to enhance the immune response. S/O nanodispersions loaded with laminarin and ovalbumin (OVA) were systematically developed and characterized in terms of particle size, in vitro OVA release behavior, and skin permeation performance using excised mouse skin. In vivo immunization via transcutaneous administration was performed to evaluate biocompatibility and antigen-specific immunoglobulin-G (IgG) responses. Laminarin-loaded S/O nanodispersions demonstrated long-term stability and efficient ex vivo skin permeability. All the prepared laminarin-loaded S/O nanodispersions showed increased OVA-specific IgG responses compared with the laminarin-free S/O formulation. Among the formulations, the S/O nanodispersion containing OVA and laminarin at a 1:4 weight ratio induced 20-fold higher OVA-specific IgG responses than PBS and 7-fold higher responses than laminarin-free S/O formulations. This study clearly demonstrates the potential of laminarin-loaded S/O nanodispersions as a non-invasive vaccine delivery platform for enhancing antigen-specific antibody responses. Full article

Background: Conventional transdermal drug delivery systems are often limited by poor skin permeability and low drug loading efficiency, necessitating the development of advanced delivery platforms. Objectives: This study aimed to develop and optimize photopolymerizable bioinks (PBs) for liquid crystal display (LCD)-based 3D printing of crosslinked hydrogel microneedles (cHMNs) to enhance transdermal delivery of estradiol valerate (E2V). Methods: A Box–Behnken design (BBD) was used to optimize the effects of Gantrez™ S-97, Jurymer™, and polyvinyl alcohol (PVA) on viscosity, exposure time, hardness, and elasticity, with strong predictive performance (R² = 0.9702–0.9907). Results: Estradiol valerate-loaded nanoparticles (E2V-NPs) were prepared via ionotropic gelation, exhibiting a particle size of 698.33 (0.78) nm, PDI of 0.50 (0.06), zeta potential of −39.09 (7.32) mV, and high encapsulation efficiency (86.87 (0.78)%). The optimized PBs enabled fabrication of uniform cHMNs (~800 µm height) with adequate mechanical strength (hardness 20.45 (1.23) N; elasticity 2.97 (0.49) MPa) and effective insertion capability. The E2V-NPs-loaded cHMNs exhibited sustained drug release over 12 days (~56.92 (4.27)%). Skin permeation studies showed a significantly enhanced flux (10.81 (4.55) µg/cm²/h) and cumulative permeation (12.94 (2.06) µg/cm²) compared to topical E2V-NPs and suspension, along with increased skin accumulation (38.55 (0.10) µg). Cytotoxicity studies confirmed that E2V and E2V-NPs were biocompatible (>80% viability), while PBs showed concentration-dependent cytotoxicity. Conclusions: Overall, this integrated platform combining design of experiment, nanoparticles, microneedles, and LCD 3D printing offered a promising strategy for enhancing transdermal drug delivery efficiency and reproducibility. Full article

Size-exclusion chromatography (SEC) or gel-permeation chromatography (GPC) is an essential tool for determining the molecular weight and polydispersity of water-soluble polymers, including biopolymers used in hydrogels, sealants, bioinks, and other biomedical materials. However, aqueous SEC of polyelectrolytes, i.e., charged polymers, is often complicated by non-size interactions among polymer chains, porous column beads, pore surfaces, frits, tubing, and mobile phase. Salt addition to eluent is commonly used to screen these interactions, but the minimum salt concentration required to restore reliable SEC behavior remains poorly defined, and excessive salt may introduce tailing, refractive-index artifacts, deposits, or instrument concerns. In this study, aqueous SEC with refractive index (RI) and right-angle light scattering (RALS) detection was used to evaluate the effect of salt ($\mathrm{N}{\mathrm{a}}_2\mathrm{S}{\mathrm{O}}_4$) concentration on poly(ethylene oxide) (PEO), a nominally neutral reference standard polymer, and sodium alginate as a model anionic biopolymer. PEO retained a single bell-shaped peak across the tested salt range, but its elution volume and SEC/RALS-derived molecular weights varied slightly with salt concentration, showing that even a nominally neutral reference polymer is affected by mobile-phase conditions. Alginate showed much stronger salt dependence: eluent at very low salt concentration produced broad, noisy, and convoluted chromatograms, whereas increasing salt concentration progressively narrowed the main peak. The first condition that produced a clear, approximately symmetric RI/RALS main peak was $6.25\times {10}^{-3} \mathrm{M}$ $\mathrm{N}{\mathrm{a}}_2\mathrm{S}{\mathrm{O}}_4$, identifying it as the minimum effective salt concentration for this alginate/column/instrument system. To rigorously validate these observations, we propose a set of both qualitative and quantitative peak analyses that objectively confirm the optimal mobile-phase conditions. Ultimately, these results provide a practical workflow for identifying the minimum effective salt concentration required for reliable SEC analysis of water-soluble polymers. Full article

2-Ethylhexyl-4-methoxycinnamate (EHMC) is among the most widely adopted organic UVB filters in commercial sunscreens. Nevertheless, its practical application potential is limited by unfavorable formulation compatibility and safety risks stemming from systemic exposure after topical administration. In this study, an oil-continuous structured gel matrix consisting of EHMC, disteardimonium hectorite (DDH) and dextrin palmitate (DP) was constructed to enhance UVB photoprotection and modulate the plasma exposure profile of EHMC following topical application. Comprehensive characterizations including rheology, XRD, Raman spectroscopy, FTIR spectroscopy, TGA and SEM collectively revealed that the combined incorporation of DDH and DP facilitates matrix structural rearrangement, enables EHMC to bind within the structured network, and promotes the formation of more intact continuous surface films. In vitro SPF assays demonstrated that the finished topical formulation SC-4 delivered superior UVB blocking efficacy compared with the EHMC-only control SC-1; furthermore, SC-4 exhibited improved short-term physical stability under the preset thermal and centrifugal acceleration test conditions. Follow-up skin safety assessments, mass spectrometry imaging (MSI) and pharmacokinetic assays verified that SC-4 elicited no remarkable acute skin irritation across all experimental conditions. Relative to SC-1, the reference formulation with EHMC as the sole UV filter, SC-4 displayed weaker EHMC-related distribution signals in skin tissues, accompanied by lower early plasma EHMC concentrations and a slightly lower AUC_0–48h trend. Collectively, these findings indicate that DDH/DP co-assembly serves as a viable matrix-structuring strategy to modulate EHMC-related skin distribution and early plasma exposure. Further research into UVA blocking performance, photostability, skin retention and transdermal permeation profiles, as well as long-term storage stability, is required to advance the development of broad-spectrum sunscreen formulations built on this novel matrix platform. Full article

This study aimed to improve the mechanical integrity of Styrofoam membranes fabricated from post-consumer food packaging. To this end, 3D-printing byproduct—thermoplastic polyurethane (TPU) waste—was blended with polyimide (PI) in the membrane dope solution. The synthesized flat-sheet upcycled membranes were evaluated via scanning electron microscopy (SEM), water contact angle (WCA), and tensile testing, while separation efficiency was determined through bovine serum albumin (BSA) rejection and permeation trials. Findings indicate that incorporating TPU into the Styrofoam/PI matrix increased tensile strength by 50%, BSA rejection by 12.4%, and permeation by 33%. Compared with pristine Styrofoam membranes, tensile strength and BSA rejection improved by 240% and 46%, respectively. Although the blend membranes exhibited a reduction in water flux (from 214 to 162.5 LMH/bar) due to pore contraction, they maintained high rejection rates (~86%) for large macromolecules like PVP (1300 kDa). Furthermore, while all membranes remained hydrophilic, hydrophobicity scaled with TPU concentration. Full article

Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol^® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article

Forward osmosis (FO) membranes are commonly evaluated through macroscopic observables such as water flux and reverse solute flux. However, these quantities do not necessarily reveal whether water permeation and solute leakage remain governed by the same dominant transport pathways, particularly in heterogeneous nanostructured membranes where selective nanochannels and defect-mediated pores can contribute differently to solvent and solute transport. Here, we introduce a hierarchical diagnostic framework to assess transport coherence loss in heterogeneous FO membranes. The framework comprises a baseline model (BM), an extended model (EM) including chemistry–geometry coupling through accessibility loss, and a full model (FM) incorporating selective pore-size heterogeneity. The ratio of reverse solute flux to water flux $R_J=J_s/J_w$ is used as a regime-based diagnostic descriptor of transport organisation, while its normalised form maps coherence variations across the state-space defined by structural selectivity and nanochemical state. The results show that chemistry–geometry coupling produces the first clear reorganisation of the coherence landscape, whereas pore-size heterogeneity mainly broadens the response while preserving its dominant topology. Simulations based on both Monte Carlo and experimentally derived pore-size distributions show consistent trends. Overall, the BM–EM–FM hierarchy offers an interpretable framework for describing transport coherence loss and the emergence of leakage-prone regimes in heterogeneous FO membranes. Full article

Background: 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a postbiotic gut microbiota-derived flavanol metabolite with reported anti-inflammatory activity. Despite growing interest in its potential dermatological applications, its pharmaceutical properties and suitability for topical delivery have not been systematically investigated. This study aimed to perform the first comprehensive preformulation and formulation-oriented evaluation of DHPV and to develop stable topical ointment formulations suitable for further dermatological research. Methods: The physicochemical properties of DHPV were characterized using powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), quantitative solubility assessment, and excipient compatibility studies. Based on the obtained preformulation data, two anhydrous ointment formulations containing DHPV were developed. The formulations were evaluated for homogeneity, rheological behavior, chemical stability under accelerated storage conditions, and in vitro drug release performance. Results: DHPV was identified as a crystalline compound with heterogeneous particle morphology and limited aqueous solubility. Quantitative solubility studies demonstrated the highest solubility in PEG 300 and glycol-based solvents. Compatibility testing revealed increased impurity formation in hydrophilic environments, whereas lipophilic excipients provided improved chemical stability. Both ointment formulations exhibited acceptable physical characteristics and maintained DHPV stability throughout accelerated storage. However, marked differences in release behavior were observed. The lipid–wax formulation showed significantly higher release rates, lower variability, and more reproducible release profiles than the petrolatum-based reference formulation, indicating more efficient diffusion of DHPV from the semisolid matrix. Conclusions: The physicochemical characteristics of DHPV strongly influence formulation design and performance. Anhydrous lipid-based systems provide a favorable environment for maintaining DHPV stability, while formulation composition significantly affects drug release. The developed lipid–wax formulation represents a promising platform for future skin permeation, pharmacodynamic, and efficacy studies. Full article