Search Results (2,582)

The cosmetics industry has been seeking to develop products with renewable natural ingredients to reduce the use of or even replace synthetic substances. Biosurfactants can help meet this demand. These natural compounds are renewable, biodegradable, and non-toxic or have low toxicity, offering minimal risk to humans and the environment, which has attracted the interest of an emerging consumer market and, consequently, the cosmetics industry. The aim of the present study was to produce a biosurfactant from the yeast Starmerella bombicola ATCC 22214 cultivated in a mineral medium containing 10% soybean oil and 5% glucose. The biosurfactant reduced the surface tension of water from 72.0 ± 0.1 mN/m to 33.0 ± 0.3 mN/m after eight days of fermentation. The yield was 53.35 ± 0.39 g/L and the critical micelle concentration was 1000 mg/L. The biosurfactant proved to be a good emulsifier of oils used in cosmetic formulations, with emulsification indices ranging from 45.90 ± 1.69% to 68.50 ± 1.10%. The hydrophilic–lipophilic balance index demonstrated the wetting capacity of the biosurfactant and its tendency to form oil-in-water (O/W) emulsions, with 50.0 ± 0.20% foaming capacity. The biosurfactant did not exhibit cytotoxicity in the MTT assay or irritant potential. Additionally, an antioxidant activity of 58.25 ± 0.32% was observed at a concentration of 40 mg/mL. The compound also exhibited antimicrobial activity against various pathogenic microorganisms. The characterisation of the biosurfactant using magnetic nuclear resonance and Fourier transform infrared spectroscopy revealed that the biomolecule is a glycolipid with an anionic nature. The results demonstrate that biosurfactant produced in this work has potential as an active biotechnological ingredient for innovative, eco-friendly cosmetic formulations. Full article

The encapsulation of bioactive compounds using proteins as wall materials has emerged as an effective strategy to enhance their stability, bioavailability, and controlled release. Proteins offer unique functional properties, including amphiphilic behavior, gel-forming ability, and interactions with bioactives, making them ideal candidates for encapsulation. Animal-derived proteins, such as whey and casein, exhibit superior performance in stabilizing lipophilic compounds, whereas plant proteins, including soy and pea protein, demonstrate greater affinity for hydrophilic bioactives. Advances in protein modification and the formation of protein–polysaccharide complexes have further improved encapsulation efficiency, particularly for heat- and pH-sensitive compounds. This review explores the physicochemical characteristics of proteins used in encapsulation, the interactions between proteins and bioactives, and the main encapsulation techniques, including spray drying, complex coacervation, nanoemulsions, and electrospinning. Furthermore, the potential applications of encapsulated bioactives in functional foods, pharmaceuticals, and nutraceuticals are discussed, highlighting the role of emerging technologies in optimizing delivery systems. Understanding the synergy between proteins, bioactives, and encapsulation methods is essential for developing more stable, bioavailable, and sustainable functional products. Full article

Oral delivery of hydrophobic compounds remains challenging due to their poor aqueous solubility and the potential toxicity associated with conventional surfactant-based emulsions. To address these issues, we present a surfactant-free encapsulation strategy using electrosprayed alginate hydrogel beads for the stable and controlled delivery of hydrophobic oils. Hydrophobic compounds were dispersed in high-viscosity alginate solutions without surfactants via ultrasonication, forming kinetically stable oil-in-water dispersions. These mixtures were electrosprayed into calcium chloride baths, yielding monodisperse hydrogel beads. Higher alginate concentrations improved droplet sphericity and suppressed phase separation by enhancing matrix viscosity. The resulting beads exhibited stimuli-responsive degradation and controlled release behavior in response to physiological ionic strength. Dense alginate networks delayed ion exchange and prolonged structural integrity, while elevated external ionic conditions triggered rapid disintegration and immediate payload release. This simple and scalable system offers a biocompatible platform for the oral delivery of lipophilic active compounds without the need for surfactants or complex fabrication steps. Full article

In this study, a new, patented form of a water-soluble cannabidiol (CBD) complex was synthesised and tested. The formation of the complex is based on the interactions, presumably through hydrogen bonding, between cannabidiol and glucosamine, the latter contributing significantly to the increased hydrophilicity. The complex was characterised by chromatography, thermal analysis, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and permeability tests. This complex has a substantially higher water solubility than normal CBD. Permeability tests indicate that it has almost five times lower permeability through lipophilic membranes and less than half the membrane mass retention of conventional CBD. At the same time, its equilibrium concentration is almost four times higher than that of normal CBD. These results suggest that this new form of CBD is a promising candidate for future biological and clinical studies, as it offers improved bioavailability and biodistribution. Full article

The integration of nanotechnology and green synthesis strategies provides innovative solutions in biomedicine. This study focuses on the biofabrication of silver nanoparticles (AgNPs) using Corynespora smithii, an endophytic fungus isolated from Bergenia ciliata. The eco-friendly synthesis process employed fungal extracts as reducing and stabilizing agents thereby minimizing the need for hazardous chemicals. The AgNPs demonstrated strong potent biological activities, showcasing significant antioxidant, antibacterial, and anticancer properties. The antibacterial efficacy was demonstrated against various Gram-positive and Gram-negative bacteria, while cytotoxicity on the A549 lung cancer cell line revealed an IC₅₀ value of 10.46 µg/mL. A molecular docking analysis revealed interactions between the major bioactive compound, dimethylsulfoxonium formylmethylide, and the pathogenic proteins, Staphylococcus aureus and Salmonella typhi, displaying moderate binding affinities. Furthermore, the ADME analysis of dimethylsulfoxonium formylmethylide indicated favourable pharmacokinetic properties, including high gastrointestinal absorption, minimal lipophilicity, and low potential for drug–drug interactions, making it a promising candidate for oral drug formulations. These findings further support the compound’s suitability for biomedical applications. This research emphasizes the potential of C. smithii as a sustainable source for synthesizing bioactive nanoparticles, paving the way for their application in developing novel therapeutic agents. This study highlights the significance of harnessing endophytic fungi from medicinal plants for sustainable nanotechnology advancements. Full article

Cucurbita pepo (CP) seeds are traditionally used to alleviate lower urinary tract symptoms associated with benign prostatic hyperplasia and overactive bladder. While these effects are often attributed to lipophilic constituents, recent studies have highlighted the therapeutic potential of oil-free hydroethanolic extracts. However, their composition remains insufficiently characterized, considering the species’ significant phenotypic and phytochemical variability. This study aimed to characterize the phytochemical profile of hydrophilic hydroethanolic seed extracts from ten CP cultivars originating from different European regions, with a focus on compositional variability. The elemental composition, along with primary and secondary metabolites, was analyzed using established spectroscopic and chromatographic methods. The extracts showed considerable variation in protein (45.39 to 114.58 mg/g dw) and free amino acid content (46.51 to 111.10 mg/g dw), as well as differences in elemental composition. Principal component analysis revealed distinct clustering patterns, with several samples displaying metabolite profiles comparable to the Cucurbita pepo var. styriaca variety currently recommended by the European Pharmacopoeia (Ph. Eur.) and the Committee on Herbal Medicinal Products (HMPC). These findings open the possibility of using other CP varieties as alternative sources for extract preparation and offer novel insights into the composition of less explored hydrophilic extracts derived from CP seeds. Full article

Background/Objectives: Oncogenic KRAS drives ~30% of solid tumours, yet the only approved G12C-specific drugs benefit ≈ 13% of KRAS-mutant patients, leaving a major clinical gap. We sought mutation-agnostic natural ligands from Ziziphus lotus, whose stereochemically rich phenolics may overcome this limitation by occupying the SI/II (Switch I/Switch II) groove and locking KRAS in its inactive state. Methods: Phytochemical mining yielded five recurrent phenolics, such as (+)-catechin, hyperin, astragalin, eriodictyol, and the prenylated benzoate amorfrutin A, benchmarked against the covalent inhibitor sotorasib. An in silico cascade combined SI/II docking, multi-parameter ADME/T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) filtering, and 100 ns explicit solvent molecular dynamics simulations. Pharmacokinetic modelling predicted oral absorption, Lipinski compliance, mutagenicity, and acute-toxicity class. Results: Hyperin and astragalin showed the strongest non-covalent affinities (−8.6 kcal mol⁻¹) by forging quadridentate hydrogen-bond networks that bridge the P-loop (Asp30/Glu31) to the α3-loop cleft (Asp119/Ala146). Catechin (−8.5 kcal mol⁻¹) balanced polar anchoring with entropic economy. ADME ranked amorfrutin A the highest for predicted oral absorption (93%) but highlighted lipophilic solubility limits; glycosylated flavonols breached Lipinski rules yet remained non-mutagenic with class-5 acute-toxicity liability. Molecular dynamics trajectories confirmed that hyperin clamps the SI/II groove, suppressing loop RMSF below 0.20 nm and maintaining backbone RMSD stability, whereas astragalin retains pocket residence with transient re-orientation. Conclusions: Hyperin emerges as a low-toxicity, mutation-agnostic scaffold that rigidifies inactive KRAS. Deglycosylation, nano-encapsulation, or soft fluorination could reconcile permeability with durable target engagement, advancing Z. lotus phenolics toward broad-spectrum KRAS therapeutics. Full article

Novel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and ABTS assays. Hydroxybutyl esters and hydroxyphenylacetic acids were used as starting materials for the synthesis of novel lipophilic diesters (butyl diarylacetates) using Mitsunobu reaction. The final products were isolated in moderate to good yields (40–78%), and their structure–antioxidant activity relationships are discussed. Compounds bearing the catechol moiety on one of the two aromatic rings and high lipophilicity proved to be the strongest antioxidants and were selected for testing as antibacterials against Staphylococcus aureus and Escherichia coli, obtaining preliminary and promising results. Full article

The number of newly developed substances with poor water solubility continually increases. Therefore, specialized formulation strategies are required to overcome the low bioavailability often associated with this property. This review provides an overview of novel physical modification strategies discussed in the literature over the past decades and focuses on oral dosage forms. A distinction is made between ‘brick-dust’ molecules, which are characterized by high melting points due to the solid-state properties of the substances, and ‘grease-ball’ molecules with high lipophilicity. In general, the discussed strategies are divided into the following three main categories: drug nanoparticles, solid dispersions, and lipid-based formulations. Full article

Modified oligonucleotides (oligos) are widely used as convenient tools in many scientific fields, including biomedical applications and therapies. In particular, oligos with lipophilic groups attached to the backbone ensure penetration of the cell membrane without the need for transfection. This study examines the interaction between amphiphilic DNA duplexes, in which one of the chains contains a lipophilic substituent, and several DNA repair proteins, particularly DNA-damage-dependent PARPs, using various biochemical approaches. DNA with a lipophilic substituent (LS-DNA) demonstrates more efficient binding with DNA damage activated poly(AD-ribose) polymerases 1-3 (PARP1, PARP2, PARP3) and DNA polymerase β. Chemically reactive LS-DNA derivatives containing a photoactivatable nucleotide (photo-LS-DNAs) or a 5′ deoxyribose phosphate (dRP) group in the vicinity of double-strand breaks (DSBs) are used for the affinity labelling of PARPs and other proteins in several whole-cell extracts of human cells. In particular, photo-LS-DNAs are used to track the level of Ku antigen in the extracts of neuron-like differentiated SH-SY5Y, undifferentiated SH-SY5Y, and olfactory epithelial cells. In vitro, PARP1–PARP3 are shown to be able to slowly excise the 5′ dRP group at DSBs. LS-DNAs can activate PARP1 and PARP2 for autoPARylation, albeit less effectively than regular DNA duplexes. Full article

A series of eleven new N-alkyl 3-(3-benzyloxyquinoxalin-2-yl) propanamides were prepared based on the azide coupling of 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide with a variety of primary and secondary amines and the consequent conjunction of a broad spectrum of lipophile and hydrophile characters to a quinoxaline ring system. 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide was produced in a two-step reaction of methyl 3-(3-oxo-3,4-dihydroquinoxalin-2-yl) propanoate with benzyl chloride followed by the hydrazinolysis of the corresponding ester. The antiproliferative activity of the compounds was tested in various cancer cell lines, including PC-3, Hela, HCT-116, and MCF-7; they showed a wide spectrum of activity for most of the tested compounds. Compound 6k exhibited the highest activity, which was comparable to that of doxorubicin, with IC₅₀ (µM) values of 12.17 ± 0.9, 9.46 ± 0.7, 10.88 ± 0.8, and 6.93 ± 0.4 µM compared to 8.87 ± 0.6, 5.57 ± 0.4, 5.23 ± 0.3, and 4.17 ± 0.2 µM for doxorubicin against Hela, HCT-116, and MCF-7, respectively. The in silico mechanistic study revealed the inhibition of HDAC-6 through the binding of the unique zinc finger ubiquitin-binding domain (HDAC6 Zf-UBD). The docking results showed a specific binding pattern that emphasized the crucial role of the quinoxaline ring and its substituents. The newly developed derivatives were evaluated for antitumor effects against four cancer cell lines PC-3, HeLa, HCT-116, and MCF-7. This research led to the identification of a quinoxaline-based scaffold exhibiting broad-spectrum antiproliferative activity and a distinct mechanism involving binding to HDAC6 Zf-UBD. The findings highlight its potential for further optimization and preclinical studies to support future anticancer drug development. Full article

Background/Objectives: In the context of preclinical studies, we have hitherto showcased that a low-molecular-weight ruthenium(III) complex we named AziRu holds significant potential for further developments as an anticancer candidate drug. When appropriately converted into stable nanomaterials and delivered into tumor cells, AziRu exhibits superior antiproliferative activity, benefiting from a multimodal mechanism of action. The activation of regulated cell death (RCD) pathways (i.e., apoptosis and autophagy) has been proved in metastatic phenotypes, including triple-negative breast cancer (TNBC) cells. This study focuses on a bioengineered lipophilic derivative of AziRu, named PalmiPyRu, that we are currently developing as a potential anticancer drug in preclinical studies. When delivered in this way, AziRu confirms a multimodal mechanism of action in effectively blocking the growth and proliferation of TNBC phenotypes. Special focus is reserved for the activation of the ferroptotic pathway as a consequence of redox imbalance and interference with iron homeostasis, as well as the glutathione biosynthetic pathway. Methods: Human preclinical models of specific TNBC phenotypes and healthy cell cultures of different histological origin were selected. After in vitro treatments, cellular responses were carefully analyzed, and targeted biochemical and molecular biology experiments coupled to confocal microscopy allowed us to explore the antiproliferative effects of PalmiPyRu. Results: In this study, we unveil that PalmiPyRu can enter TNBC cells and interfere with both the iron homeostasis and the cystine-glutamate antiporter system Xc-, causing significant oxidative stress and the accumulation of lipid oxidation products. The increase in intracellular reactive free iron and depletion of glutathione engender a lethal condition, driving cancer cells toward the activation of ferroptosis. Conclusions: Overall, these outcomes allow us, for the first time, to couple the antiproliferative effect of a ruthenium-based candidate drug with the inhibition of the Xc- antiporter system and Fenton chemistry, thereby branding PalmiPyRu as an effective multimodal inducer of ferroptosis. Molecular mechanisms of action deserve further investigations, and new studies are underway to uncover how interference with Xc- controls cell fate, allowing us to explore the connection between iron metabolism regulation, oxidative stress and RCD pathways activation. Full article

This study aims to provide a comprehensive evaluation of the bioactive compounds present in honeysuckle flower (Lonicera japonica Thunb.) extract (HSF) and their remarkable antioxidant activity. A docking simulation was performed to clarify the binding affinities of the identified phytochemicals to enzymes associated with anti-aging and anti-inflammatory activities. In addition, the low-energy nanoemulsions based on optimally formulated polyglycerol fatty acid esters (PGFEs), developed through D-optimality, were designed for the incorporation of HSF extract. The result revealed that HSF is a rich source of diverse phenolic and flavonoid compounds that contribute to its remarkable antioxidant capacity. Molecular docking analysis indicates that its compounds exhibit anti-aging and anti-inflammatory activities, particularly through collagenase, hyaluronidase, and TNF-α inhibition. Furthermore, D-optimality revealed that HSF-loaded nanoemulsions can be fabricated by a surfactant to oil ratio (SOR) of 2:1 with a ratio of low hydrophilic-lipophilic balance (HLB) surfactant to high HLB surfactant (LHR) of 1:2. Polyglyceryl-6 laurate as a high HLB surfactant produced the optimal nanoemulsion with small particle size and possessed an encapsulation efficiency (EE) of 74.32 ± 0.19%. This is the first report to combine D-optimal design-based nanoemulsion development with a multi-level analysis of HSF, including phytochemical profiling, antioxidant evaluation, and in silico molecular docking. These findings highlight that HSF-loaded polyglycerol fatty acid ester-based nanoemulsions could be a skin health-promoting ingredient and effective alternative for a variety of skincare applications. Full article

Background: Liposomes and, more recently, structured nanolipid particles have demonstrated effectiveness as carriers for delivering hydrophilic or lipophilic anticancer agents, enhancing their biocompatibility, bioavailability, and sustained release to target cells. Objective: Herein, four doxorubicin formulations—comprising either the acidic or neutral form—were encapsulated into liposomes (Lipo) or nanostructured lipid carriers (NLCs) and characterized in terms of size, entrapment efficiency, morphology, and effects on two cancer cell lines (melanoma B16-F10 and breast carcinoma Walker 256 cells). Methods and Results: While liposomal formulations containing acidic doxorubicin displayed IC₅₀ values ranging from 1.33 to 0.37 µM, NLC-based formulations, particularly NLC-Doxo@Ac, demonstrated enhanced cytotoxicity with IC₅₀ values as low as 0.58 µM. Neutral Doxorubicin demonstrated lower cytotoxicity in both the nanoformulations and cell lines. Differences were also observed in their internalization patterns, cell-cycle impact, and apoptotic/necrotic effects. Compared to liposomes, NLCs exhibited distinct internalization patterns and induced stronger cell-cycle arrest and necrosis, especially in melanoma cells. Notably, NLC-Doxo@Ac outperformed liposomal counterparts in melanoma cells, while liposomal formulations showed slightly higher efficacy in Walker cells. Early and late apoptosis were more pronounced in Walker cells, whereas necrosis was more prominent in melanoma B16-F10 cells, particularly with the nanolipid formulations. Conclusions: These results correlated positively with cell-cycle measurements, highlighting the potential of NLCs as an alternative to liposomes for the delivery of neutral or acidic doxorubicin, particularly in tumor types that respond poorly to conventional formulations. Full article

Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit^® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article