Search Results (153)

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

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

This study evaluated the influence of four thermal pretreatment techniques—autoclaving, hot-air oven treatment, hot-water immersion, and microwave irradiation—on Parthenium hysterophorus biomass to improve its biodegradability and biogas generation potential under batch anaerobic digestion. Among the investigated methods, hot-air oven pretreatment at 110 °C for 90 min exhibited the most significant enhancement in biomass solubilization, as indicated by a 51.5% rise in soluble chemical oxygen demand (sCOD) and an increase in volatile fatty acids (VFAs) compared with the untreated control. These compositional improvements facilitated faster hydrolysis and led to a 25.73% higher cumulative methane yield in biochemical methane potential (BMP) assays. Structural analysis revealed pronounced alterations in the lignocellulosic matrix, with reductions in hemicellulose and partial delignification improving substrate accessibility. Complementary characterisation using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) confirmed the disruption of crystalline cellulose regions and modification of functional groups, supporting the observed biochemical improvements. Collectively, the results demonstrate that hot-air oven pretreatment is a practical and energy-efficient approach for enhancing the digestibility of P. hysterophorus biomass, promoting its utilisation as a sustainable feedstock for renewable biogas production and environmental management of this invasive weed. Full article

The overreliance on non-renewable phosphate fertilizers necessitates sustainable alternatives for phosphorus recycling in agriculture. This study aimed to characterize and enhance the metabolic activity of phosphate-solubilizing microorganisms isolated from compost by eliciting them with two distinct mesoporous silica nanoparticles: standard SBA-15-S and short-pore SBA-15-C. Bacterial strains with broad-spectrum P solubilization and mineralization capacities were isolated from the mesophilic phases of tomato greenhouse and cow manure composts. These isolates received treatment with nanoparticle concentrations of 0.1, 10, and 100 ppm. The results demonstrated that nanoparticle elicitation significantly altered microbial growth, solubilization halos on tricalcium phosphate, and the specific activity of acid, neutral, and alkaline phosphatases in a strain- and nanoparticle-dependent manner. Notably, SBA-15-C at 100 ppm consistently enhanced multiple P-recycling properties across several strains, including Proteus and Myroides species. Principal component analysis revealed distinct behavioral clusters between composting phases and isolation methods. The findings indicate that tailored silicon oxide nanostructures can serve as eustressors to modulate and enhance the P-solubilizing and mineralizing functions of compost-derived microbiota, offering a promising nanobiostimulation strategy for developing enhanced biofertilizers. Full article

Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. At present, multi-agent chemotherapy and surgery provide only limited effects and the prognosis for patients with recurrent or metastatic disease remains poor, with 5-year survival rates below 30%. These challenges highlight the need for innovative therapeutic approaches targeting osteosarcoma more effectively. Fenretinide, a synthetic derivative of all-trans retinoic acid, has shown significant antitumor activity in various cancers. In a recent high-throughput drug screening study, fenretinide emerged as the most active molecule against diffuse midline glioma over more than 3500 compounds. Fenretinide also demonstrated cytotoxic activity against osteosarcoma cell lines in vitro and in preclinical models and is endowed with a favorable safety and toxicity profile. However, its poor water solubility and limited bioavailability have hindered its clinical translation. To improve fenretinide bioavailability and enhance tumor exposure, different nanotechnology-based drug delivery systems have been proposed. Here we propose a tertiary complex made of fenretinide, bovine serum albumin, and hydroxypropyl-betacyclodextrin, indicated as BSAF. Methods: BSAF was evaluated for the main physico-chemical parameters such as hydrodynamic size, zeta potential, stability to drug leakage, and the biological effect on the osteosarcoma cell line MG63. Results: BSAF showed hydrodynamic size at the nanoscale, enhanced drug solubilization, high drug loading and size stability to dilution, characteristics that make this complex useful for targeted therapy. When tested on the MG63 osteosarcoma cell line, BSAF demonstrated significantly enhanced cytotoxicity, with half-maximal inhibitory concentration (IC₅₀) values ~50% lower than free fenretinide. The complex was more efficient than free fenretinide in inhibiting cell migration as demonstrated by wound healing assay. Live-cell imaging analyses revealed a cytostatic effect at sub-cytotoxic concentrations. Specifically, treatment with concentrations below the IC₅₀ resulted in significantly prolonged cell doubling time, decreased cell divisions, increased cellular sphericity and thickness, and decreased cell area. These morphological changes are more consistent with cell cycle arrest rather than apoptosis. These findings were corroborated by stable dry mass measurements, an indication of a cytostatic state rather than progressive cell death. In addition, cell motility parameters (e.g., instantaneous velocity, track speed, and displacement) at the single-cell and population level were markedly reduced at sub-IC₅₀ concentrations, further supporting a cytostatic phenotype. Conclusions: Collectively, the new BSAF complex showed promise as a potential therapeutic agent for treating osteosarcoma cancer, due to the favorable physico-chemical characteristics and the cytotoxic/cytostatic effects on MG63 cells. BSAF effects may be therapeutically valuable, particularly in preventing tumor recurrence by suppressing the proliferative and migratory potential of residual drug-resistant clones. Unlike conventional anticancer agents that mainly rely on cell death, fenretinide, when complexed, demonstrates a dual capacity to induce both cytotoxic and cytostatic responses, depending on concentrations, potentially overcoming multiple resistance mechanisms that are generally associated with tumor exposure to drug sub-cytotoxic concentrations. Full article

This study evaluated the effects of two euthanasia methods (blanching, blast freezing) and two drying methods (oven drying, freeze drying) on protein extractability, oil recovery, lipid oxidation, and nutritional composition of mealworm-derived full-fat flours, defatted flours, and protein concentrates. Protein extraction yields differed significantly among treatments (ANOVA, p < 0.001), except between blanched + freeze-dried and blast-frozen + oven-dried samples. Blast freezing resulted in higher protein extraction yields than blanching. Blast freezing markedly increased acid values (>40 mg KOH/g oil) relative to blanching (<5 mg KOH/g), while freeze drying increased peroxide values more than tenfold compared with oven drying. Ash contents ranged from 4 to 8% without a treatment effect. Defatting significantly reduced oil content and increased protein and chitin contents. Chitin was nearly absent in protein concentrates. In blast-frozen + oven-dried protein concentrates, the oil content was significantly up-concentrated compared with defatted samples. P, Mg, and K significantly increased in defatted samples, while protein extraction reduced Mg, K, and Ca but increased Na due to alkaline solubilization. Micromineral profiles were most affected in protein concentrates, with increases in Cu and Fe and minor decreases in Mn. Overall, euthanasia and drying methods influence yield and quality, highlighting the need for tailored, scalable processing strategies for mealworm-based food and feed applications. Full article

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been identified as forever chemicals and pose a serious threat to the environment due to their stable C–F bond. The current methods are ineffective or costly for PFAS remediation. In response, this study develops a dielectric barrier discharge (DBD) air plasma system capable of simultaneously treating perfluorooctanoic acid (PFOA)-contaminated wastewater and enhancing waste-activated sludge (WAS) solubilization through the subsequent use of plasma-activated water (PAW). Air plasma achieved 94% PFOA degradation and 32% defluorination within 40 min—substantially outperforming Ar and N₂ plasma—due to the co-generation of hydrated electrons (e_aq⁻), ^•OH, and reactive nitrogen species (RNS). Scavenging experiments confirmed that e_aq⁻ is the primary initiator of C–F bond cleavage, while H₂O₂ and NO₂⁻ synergistically form peroxynitrous acid (ONOOH), further promoting chain-shortening reactions. UPLC-MS identified PFHpA, PFHxA, PFPeA, and PFBA as key intermediates. The air plasma effluent contained high concentrations of NO₂⁻-N and H₂O₂ under acidic conditions, enabling PAW to induce strong oxidative stress on WAS, resulting in significant extracellular polymeric substance (EPS) release (DOC up to 134 mg/L), improved sludge filterability (capillary suction time (CST) reduced by ~85%), and shifts in microbial community. This study presents a dual-functional air plasma approach that enables both PFAS degradation and sludge treatment, improving the overall competitiveness and applicability of plasma technology for advanced wastewater treatment. Full article

There is an urgent demand for sustainable agricultural practices that minimize environmental impacts and reduce the reliance on synthetic pesticides and fertilizers. Endophytes represent a largely untapped resource of beneficial microorganisms with multiple potential applications as natural biocontrol agents and promoters of plant growth and development. This paper aimed at identifying new fungal strains and performing a series of preliminary in vitro screenings to evaluate their potential use for plant-growth promotion and antifungal activity. A total of 102 fungal endophytes were isolated from different plant tissues of seven wild relatives of barley (Brachypodium sylvaticum, Bromus hordeaceus, Bromus sterilis, Elymus farctus, Elymus repens, Leymus arenarius and Lolium perenne) that were sourced from 22 contrasting wild habitats. Fungal endophytes were isolated using standard culture-based methods and identified via DNA barcoding of the nrITS marker. Based on a literature search, a sub-group of endophytes were selected and evaluated for indole-3-acetic acid (IAA) synthesis, ammonia production and phosphorous (P) solubilization. From these, 15 endophytes were also tested for antifungal activity against Ramularia collo-cygni, Pyrenophora teres, and Gaeumannomyces tritici. All the endophytes were positive for ammonia production at variable rates, but no P solubilization nor IAA synthesis without L-tryptophan were observed. On the contrary, five promising isolates (2 Daldinia concentrica, Metapochonia suchlasporia, Chaetomium sp., and Ophiocordyceps sinensis) had mean pathogen growth inhibition rates above 80%, compared to the untreated negative controls. To the best of our knowledge, this study is the first published report that investigates natural antagonism against Ramularia collo-cygni and expands the list of endophytic strains with natural antagonism on the tested cereal pathogens. Results are discussed in the context of endophytes application to barley cultivation within the European regulatory framework. Full article

Background/Objectives: Capric acid (CA)–therapeutic deep eutectic systems (THEDES) are emerging as a distinct class of biofunctional matrices capable of reshaping drug solubilization, permeability, and bioactivity. Methods: Relevant studies on CA–THEDES were identified through targeted database searches and screened for evidence on their design, mechanisms, and pharmaceutical performance. Results: This review synthesizes current evidence on their structural design, mechanistic behavior, and pharmaceutical performance, revealing several unifying principles. Across multiple drug classes, CA consistently drives strong, directional hydrogen bonding and drug amorphization, resulting in marked solubility enhancement and stabilization of non-crystalline or supersaturated states relative to crystalline drugs or conventional solvent systems. Its amphiphilic C10 chain further contributes to membrane fluidization, which explains the improved transdermal and transmucosal permeation repeatedly observed in CA-THEDES. Additionally, synergistic antimicrobial and anticancer effects reported in several systems confirm that CA acts not only as a solvent component but as a bioactive co-therapeutic. Collectively, the reviewed data show that CA serves as a structurally determinant element whose dual hydrogen-bonding and membrane-interacting roles underpin the high pharmaceutical performance of these systems. However, gaps remain in long-term stability, toxicological profiling, and regulatory classification. Emerging Artificial Intelligence (AI) and Machine Learning (ML)-guided predictive approaches offer promising solutions by enabling rational selection of eutectic partners, optimal ratios, and property optimization through computational screening. Conclusions: Overall, CA-THEDES represent a rationally designable platform for next-generation drug delivery, where solvent functionality and therapeutic activity converge within a single, green formulation system. Full article

To effectively valorize lignin, some challenges must be addressed. First, emerging techniques based on green methods may experience difficulties during the scale-up process. Secondly, the low solubility of lignin can hinder further valorization. This study investigated the impact of lignin extraction scale-up on yield and purity and evaluated strategies to enhance lignin solubility. Lignin from grape stalks was extracted using two previously optimized methods—alkaline and deep eutectic solvents—at a scale-up by factors of 5, 10, and 20 times. Although a slight decrease in extraction yield was observed with increasing scale, lignin purity remained consistent across all conditions. After extraction, lignin samples were subjected to solubilization tests using surfactants (Tween 20, Tween 80, and polyethylene glycol) and organic solvents (ethanol and acetic acid). Results demonstrated that surfactants were notably more effective in solubilizing lignin (up to 74.5%) compared to organic solvents. Furthermore, as an alternative to lignin solubilization, the production of lignin nanoparticles through ultrasonication with minimal chemical use was also explored. Upon optimization, spherical nanoparticles with a mean diameter of approximately 200 nm were successfully obtained. The use of surfactants was necessary to avoid nanoparticle aggregation during concentration steps and to enhance colloidal stability. This study demonstrates the feasibility of scaling up lignin extraction methods and further explores two approaches to enhancing the valorization of the obtained lignin—solubilization and the production of lignin nanoparticles—thereby contributing to the development of efficient and sustainable strategies for diverse lignin-based applications. Full article

Global energy demand is projected to increase by approximately 28% by 2040, thereby intensifying the urgent need for sustainable alternatives to fossil fuels. This comprehensive review examines the integration of deep eutectic solvent (DES) pretreatment with anaerobic digestion to valorize apple pomace (AP), a major lignocellulosic by-product of the apple juice industry that is often improperly disposed of, posing substantial environmental burdens. A key challenge for efficient biofuel production from AP is its high lignin content, which inhibits complete degradation during AD. DESs have emerged as promising green pretreatment agents owing to their low toxicity, biodegradability, and selective lignocellulosic solubilization capabilities. This review critically synthesizes research on: AP compositional characteristics and disposal challenges; DES pretreatment mechanisms and comparative advantages over conventional methods; AD processes for AP, including yields and constraints; and technical, economic, and environmental aspects of DES-AD integration. Critical analysis reveals that acidic DES formulations achieve 40–60% higher delignification than neutral systems but produce higher levels of inhibitory compounds, necessitating application-specific optimization. Nonetheless, significant knowledge gaps persist, including a lack of standardized protocols, limited pilot-scale validation, and insufficient techno-economic assessments. This integrated approach closely aligns with circular economy principles, offering an environmentally friendly pathway for waste valorization while reducing reliance on fossil fuels and mitigating greenhouse gas emissions. Full article

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol^® P (diethylene glycol monoethyl ether), Capryol^® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol^® P and Capryol^® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10⁻⁵ cm²/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol^® P and Capryol^® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds. Full article

Moringa oleifera leaves are a protein-rich source containing all essential amino acids and offering high nutritional value. Ultrasound-assisted extraction (UAE) has emerged as an efficient method to improve protein recovery while enhancing the structural and functional properties of plant proteins. This study aimed to improve protein extraction from M. oleifera leaves using UAE and to characterize the nutritional composition and gel-related properties of the resulting protein concentrate. Chosen conditions were a solubilization pH of 11.68, 20 min of ultrasound treatment, and precipitation at pH 4.5, resulting in an extraction yield of 79.90% and protein content of 53.97%. Moringa oleifera leaf flour (MOF) contained 29.38% protein, 37.98% dietary fiber, and high mineral levels (1751.85 mg/100 g of calcium; 512.55 mg/100 g of magnesium). Compared with MOF, the M. oleifera protein concentrate (MOPC) showed a 21.4% increase in essential amino acids, with leucine and lysine being the most abundant. Functionally, MOPC exhibited 24.26% solubility at pH 2, complete gelation at pH 8, 58.66% emulsifying capacity with 79.52% stability at pH 10, and 21.11% foaming capacity with 94.44% stability at pH 2. The gel-forming ability was the most promising characteristic, highlighting the potential of MOPC as a natural structuring agent in gel-based food systems and functional formulations. Full article

The extensive use of submicron emulsion systems, particularly those stabilized by nonionic surfactants, with their proven effectiveness and safety profile, provides a reassuring foundation for our research. Consequently, we designed and engineered new submicron emulsion formulations stabilized with a biocompatible surfactant polyoxyethylated cocoamine, whose nonionic character is due to a high degree of polyoxyethylation. We chose oleic acid as the oil phase, a fatty acid known for its beneficial properties. This led to novel biocompatible nanoemulsions with high stability and cosurfactant-free microemulsions. The dynamic light scattering studies confirmed that both formulations have a nanometric size and low polydispersity index values. Moreover, transmission electron microscopy verified the nanodroplets’ morphological homogeneity and spherical shape. The resulting nanoplatforms can be applied to carry bioactive agents in the pharmaceutical and cosmetic fields. For this reason, we solubilized newly synthesized 5-dimethylamino-5′-nitro-2,2′-bithiophene as a model hydrophobic cargo for delivering poorly water-soluble compounds. This dye was chosen due to its strong solvatochromic behavior and suitability for micropolarity analysis via UV–Vis spectroscopy. We also present a simple method for rapid micropolarity screening to assess the type of nanodispersion via solvatochromic shift as an alternative procedure for evaluating of the oils used to fabricate nanoformulations for pharmaceutical and cosmetic purposes. Full article

Background: Skin injuries, such as chronic wounds and inflammatory skin diseases, often face limitations in treatment efficacy due to the low efficiency of transdermal drug delivery and insufficient local concentrations. Curcumin (CUR), a natural compound with anti-inflammatory and antioxidant properties, has demonstrated potential in the repair of skin damage; however, its clinical application is hindered by its physicochemical characteristics. This study constructs a novel nanocomposite drug delivery system: CUR-loaded micellar nanocomposite gel (CUR-M-DMNs-Gel). A composite system is used to achieve the efficient solubilization and enhanced transdermal permeation of CUR, thereby providing a novel formulation approach for the treatment of skin diseases. Methods: CUR-loaded micellar (CUR-M) utilizes CUR as the core active ingredient, which possesses multiple pharmacological effects including anti-inflammatory and antioxidant properties. TPGS serves as a micellar carrier that not only enhances the solubility and stability of CUR through its amphiphilic structure but also facilitates drug absorption and transport within the body. In dissolvable microneedles (DMNs), PVP K30 forms a stable three-dimensional network structure through entanglement of polymer chains, ensuring sufficient mechanical strength for effective penetration of the skin barrier. Meanwhile, PVP K90, with its higher molecular weight, enhances the backing’s support and toughness to prevent needle breakage during application. The incorporation of hyaluronic acid (HA) improves both the moisture retention and adhesion properties at the needle tips, ensuring gradual dissolution and release of loaded CUR-M within the skin. In CUR-loaded micellar gel (CUR-M-Gel), PVP K30 increases both adhesive and cohesive forces in the gel through chain entanglement and hydrogen-bonding interactions. Tartaric acid precisely regulates pH levels to adjust crosslinking density; glycerol provides a long-lasting moisturizing environment for the gel; aluminum chloride enhances mechanical stability and controlled drug-release capabilities; NP-700 optimizes dispersion characteristics and compatibility within the system. Results: In vitro experiments demonstrated that the CUR-M-DMNs-Gel composite system exhibited enhanced transdermal penetration, with a cumulative transdermal efficiency significantly surpassing that of single-component formulations. In the mouse skin defect model, CUR-M-DMNs-Gel facilitated collagen deposition and effectively inhibited the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β). In the mouse skin photoaging model, CUR-M-DMNs-Gel markedly reduced dermal thickness, alleviated damage to elastic fibers, and suppressed inflammatory responses. Conclusions: The CUR-M-DMNs-Gel system can enhance wound healing through subcutaneous localization, achieving long-term sustained efficacy. This innovative approach offers new insights into the treatment of skin injuries. Full article