Search Results (344)

Background: Overexpression of immune cell populations leads to self-amplifying cytokine loops, contributing to chronic inflammation in both allograft rejection and autoimmune conditions. Tacrolimus (TAC), despite being a potent immunosuppressant, has limitations; its systemic adverse effects include nephrotoxicity, neurotoxicity, and high variability in tissue exposure in patients. Currently available therapeutic options are limited by the lack of targeted and localized drug delivery systems, resulting in ineffective control over drug-release behavior. Moreover, TAC being highly lipophilic poses challenges for formulation development. To address these gaps, this study focuses on developing a thermoresponsive hydrogel platform comprising distinct nanocarriers for localized delivery of TAC. The nanocarriers include nanoemulsion (NE) and micelles as TAC carriers, and their particle sizes are specifically engineered at the nanoscale for differential release behavior and to support immune cell targeting (macrophages and T-cells). Incorporation into a thermoresponsive hydrogel matrix enables it to act as a local depot at the injection site and deliver TAC with a slow, extended-release profile. Methods: TAC was loaded into a coconut-rich lipid-phase-based NE via high-pressure microfluidization. Simultaneously, TAC-loaded micelles were optimized using a full-factorial design of experiments (DoE) and manufactured via the thin-film hydration method. Both nanocarriers were evaluated for long-term colloidal stability assessments. Hydrogels were produced maintaining aseptic conditions for sterile batch production. Rheological characterization was performed to assess sol-gel transition, thermoreversibility, and injectability, and in vitro release studies were conducted to evaluate TAC diffusion from the developed nanoformulations. Results: Developed nanocarriers resulted in distinct particle sizes in NE (80–85 nm) and micelles (15–17 nm) with successful TAC loading maintaining long-term colloidal stability. The developed TAC-loaded dual-nanocarrier hydrogel (Dual-HG) showed thermoresponsive behavior and gelation at 37 °C, forming as a local depot. In vitro release studies showed slow and extended tacrolimus release from hydrogels and demonstrated particle size-dependent release behavior between the NE and micelle. Conclusions: Therefore, our study highlights a novel dual nanocarrier hydrogel platform combining TAC-NE and TAC-micelle for localized delivery. The findings support that nanocarriers can be engineered to modulate drug diffusion behavior. Notably, the dual nanocarrier within a thermoresponsive hydrogel platform can be used to deliver one or multiple drugs locally, minimizing systemic exposure when sustained local immunosuppression is required. The 25 mL scale sterile batch production of hydrogels emphasizes their suitability for future translational applications. Full article

Background: Sapropelic mud from Techirghiol Lake has been used therapeutically under medical supervision for more than 170 years; however, its comprehensive physicochemical characterization under application-relevant conditions remains insufficiently documented. This study aimed to evaluate the physicochemical properties, mineral and organic composition, ion-exchange capacity, and potential therapeutic mechanisms of Techirghiol sapropelic mud. Methods: Mud samples were analyzed using standardized physicochemical and analytical techniques to determine pH, water content, granulometry, mineral composition, organic fraction, and trace elements. Results: The results indicate that Techirghiol mud is a highly hydrated alkaline peloid characterized by a complex mineral–organic system. Major elements included sodium, calcium, and magnesium, while trace elements such as manganese, iron, and zinc were present in relevant concentrations. The organic fraction, composed of humic substances, lipids, and proteins, reflected advanced but incomplete humification processes. Conclusions: The findings demonstrate the complex physicochemical composition of Techirghiol sapropelic mud and provide a scientific basis for further studies regarding its properties and applications. Full article

In industrial soybean lecithin production, process variables such as temperature, water content, agitation, and processing time play a critical role in determining the final product quality. Despite their importance, the combined effects of these parameters under industrial-scale conditions have not been sufficiently quantified. Therefore, this study systematically evaluated the influence of processing temperature (70–80 °C) and water content (1.5–3% w/w of oil) on key quality attributes, including lecithin moisture content, purity, acidy number, and peroxide value, as well as soybean oil acidity and insoluble fine substances. A response surface methodology (RSM) approach was applied to model the relationships between variables and to identify optimal processing conditions. The results indicate that an increasing temperature reduces lecithin moisture content, likely due to enhanced water evaporation and improved phase separation, while simultaneously increasing peroxide value and oil acidity (p < 0.05), possibly because of accelerated lipid oxidation and hydrolysis. Lecithin purity improved up to 75 °C, indicating more efficient separation, but decreased at higher temperatures, suggesting thermal degradation or emulsification effects. Similarly, increasing water content led to higher moisture, peroxide value, and acidy numberin lecithin, as well as increased acidity and insoluble fine substances in soybean oil (p < 0.05), which can be attributed to excessive hydration promoting emulsion stability and entrainment of oil-phase impurities into the lecithin fraction. Process optimization indicated that a water content of 1.5% and a temperature of 73.93 °C yielded the highest overall product quality, with a desirability value of 0.874. Full article

Oocyte maturation is a pivotal event in teleost reproduction that directly determines egg quality, fertilization success, and the developmental competence of early embryos. However, the transcriptional and post-transcriptional regulatory mechanisms operating within oocytes during maturation in marine teleosts remain poorly understood. In the present study, the orange-spotted grouper (Epinephelus coioides), an economically important marine aquaculture species, was used as a model. Oocytes at four distinct maturation stages were obtained by microscopically removing the surrounding follicular layers, followed by integrated mRNA-seq and miRNA-seq analyses to characterize the molecular regulatory landscape underlying oocyte maturation and hydration. The results showed that, as maturation progressed, oocyte diameter and wet weight increased significantly, accompanied by a marked decrease in Na⁺ content, a significant increase in K⁺ content, and the continuous accumulation of most free amino acids, indicating the gradual establishment of an osmotic basis favorable for oocyte hydration. Transcriptomic analysis further revealed extensive transcriptional remodeling during both the early and late phases of maturation. Differentially expressed genes were significantly enriched in pathways related to oocyte meiosis, cytokine signaling, lipid metabolism, DNA replication, cell cycle regulation, ribosome biogenesis, spliceosome function, oxidative phosphorylation, and mitochondrial activity, suggesting that oocyte maturation is a dynamic process characterized by a shift from basal growth maintenance to metabolic reprogramming, maternal transcript remodeling, and terminal maturation responses. miRNA profiling identified a large number of stage-specific differentially expressed miRNAs, including let-7d-5p, miR-22a-3p, and novel-miR-20/27/118, whose predicted target genes were mainly enriched in ribosome-related pathways, oxidative phosphorylation, DNA replication, transcriptional regulation, and signal transduction. Moreover, the miRNA–TF–mRNA regulatory network demonstrated that miRNAs may not only directly repress target genes, but also mediate hierarchical regulatory cascades through transcription factors, thereby coordinately participating in cell cycle progression, cytoskeletal remodeling, vesicular transport, and immune- and cell communication-related responses. Collectively, this study provides the first systematic temporal atlas of mRNA and miRNA regulation during oocyte maturation and hydration at the oocyte level in a marine teleost, thereby deepening our understanding of the molecular basis of meiotic resumption and egg quality formation, and offering valuable theoretical support for the optimization of artificial breeding and the identification of key molecular targets in grouper reproduction. Full article

Laser therapy is commonly associated with transient skin reactions such as erythema and edema, creating a need for effective post-procedural skincare strategies. In this study, we developed and characterized a novel bio-mask that integrates a hydrogel matrix with a lipid nanodispersion system designed to simultaneously deliver hydrophilic and hydrophobic active compounds. The key innovation of this formulation lies in the combination of a highly hydrophilic hydrogel structure with lipid nanoparticles embedded within a polymeric network, enabling enhanced bioavailability of active ingredients. Preliminary observations from instrumental measurements in a small group of healthy volunteers suggest that a single 60 min application resulted in notable improvements in skin hydration and elasticity, along with a reduction in transepidermal water loss (TEWL), erythema, and skin sensitivity. Furthermore, both the complete formulation and its individual components exhibited inhibitory activity against collagen and elastin glycation, while promoting type I procollagen synthesis. Importantly, this study provides new evidence for the synergistic interaction between hydrogel matrices and lipid nanodispersion systems in modulating skin barrier function and biochemical aging markers. The formulation, composed entirely of ingredients of natural origin, proved to be an effective carrier for active compounds and showed measurable benefits for skin hydration and barrier-related parameters. Full article

Epidermal barrier dysfunction, driven by disorganization and altered composition of the stratum corneum (SC) lipid matrix, underlies multiple inflammatory dermatoses, namely atopic dermatitis (AD). The lipid fraction derived from Black Soldier Fly larvae (BSFL) biomass has emerged as a promising biomaterial for skin health applications, particularly for restoring barrier function. Following previous work on the development of solid lipid nanoparticles (SLNs) incorporating BSFL lipid extract, the present study focused on the mechanistic evaluation of the occlusive, moisturizing and skin reinforcement potential of these nanoformulations (NFs), by exploring both in vitro and in vivo models. The compatibility assays showed no adverse effects after patch testing on healthy or atopic individuals, nor alterations on skin hydration, transepidermal water loss (TEWL), or redness. In vitro studies confirmed the ability of these NFs to form an occlusive lipid film, hampering moisture loss, with 39% reduction of water loss compared to the control. Efficacy assays in human volunteers revealed a statistically significant improvement in epidermal conditions at treated sites, evidenced by enhanced SC hydration. The plastic occlusion stress test (POST) revealed a trend toward a reduced evaporation half-life, suggesting a modulation of the epidermal water dynamics, although the effect did not reach statistical significance. Overall, BSFL-based lipid nanoparticles emerge as emollient agents with broad potential for incorporation into next-generation cosmetic and pharmaceutical products for the management of AD. Full article

The skin serves as a primary defensive barrier to protect the body from environmental contaminants, infections and trauma. Unfortunately, skin barrier’s structural and functional integrity can be compromised, disrupted or impaired due to a combination of internal and external factors, making it vulnerable and often leading to a wide range of skin conditions characterized by dryness, heightened sensitivity, and increased susceptibility to damage and infections. In addition, the integrity of the skin barrier tends to deteriorate progressively with age. As people age, their skin naturally changes and can also be compromised by a plethora of factors that reduce its strength and resilience. The aging skin becomes thinner and more sensitive, coinciding with a variety of structural–functional alterations, decreased levels of natural moisturizing factor (NMF), lipid content and hydration, increased transepidermal water loss (TEWL), altered skin surface pH (pHss) and microbiome diversity. All these age-related skin integrity alterations make the skin drier, flakier, itchy, and fragile, and more susceptible to damage and breakdown, thus diminishing its ability to effectively protect, repair and heal efficiently. Identifying skin integrity issues before they progress will foster positive outcomes through effective preventive measures. Hence, it is important to understand the impact of skincare formulations on skin integrity in compromised aging skin. A well-considered, evidence-based approach to skincare can provide cleansing, moisturizing and protective benefits, while aiding the reduction in skin integrity issues like dry and itchy skin, sensitive skin, bruising, skin tears, pressure injuries (PIs), lower leg ulcers and moisture-associated skin damage (MASD). Managing skin integrity in compromised aging skin begins with gentle skin cleansing, adequate moisturization and protective barrier care to ensure the skin’s function is maximized. Full article

Lipid nanoparticles (LNPs) have become the cornerstone of nucleic acid delivery platforms, particularly in RNA-based vaccines and therapeutics. However, the conventional methods of LNP production, which are primarily reliant on microfluidic mixing of aqueous and organic solvent phases, pose limitations in terms of mRNA stability, residual organic contamination, scalability, cost, and environmental impact. These limitations prompted a renewed search for non-conventional strategies with the promise of improving mRNA-LNP encapsulation approaches. These emerging approaches aim to address key bottlenecks, including mRNA hydrolysis-driven degradation, high production losses, and complex downstream purification. Moreover, the ability to decouple LNP synthesis from mRNA encapsulation could enable streamlined, modular manufacturing workflows and customizable payload delivery, including single- or multiple-mRNA payloads, thereby expanding the therapeutic scope of LNPs. This review offers an early insight into the design principles and scalability potential of emerging non-conventional LNP encapsulation approaches, including solvent-free and microfluidics-free methodologies, and pre-built LNP workflows. We also examine trends in emerging LNP encapsulation tools, including high-shear mixing, sonication, membrane contraction, and other approaches. Finally, we extrapolate the suitability of the methods for scale-up approaches and their economic implications based on the process information. Full article

The obligate mutualism between Ficus and its pollinating wasps provides a suitable system to investigate these dynamics because it encompasses two contrasting pollination modes: active and passive. Here we compared pollen traits in an actively pollinated fig tree, Ficus citrifolia, and a passively pollinated species, F. obtusiuscula, examining pollen both at anther presentation and after deposition on the bodies of their pollinating wasps. Pollen morphology, hydration-related behavior, cytology, and reserve composition were characterized using scanning electron microscopy (conventional and modified), light and transmission electron microscopy, histochemical assays, and viability tests. Across species, pollen traits at anthesis showed broad overlap in morphology, viability and major reserve classes, indicating that these characteristics are not consistently predicted by pollination mode alone. In both species, pollen was bicellular, harmomegathic and highly viable at presentation, consistent with resilience during transport. The main divergence emerged after pollen transfer to the pollinator. In the actively pollinated species, pollen recovered from wasp thoracic pockets exhibited pronounced intracellular remodeling, including vacuolization, starch depletion, lipid redistribution and localized cytoplasmic degradation. By contrast, pollen of the passively pollinated species retained a comparatively stable cytological organization after transport despite changes in reserve distribution. These results suggest that the more pronounced cytoplasmic reorganization observed in the pollen of the actively pollinated species after deposition on the wasp body may represent a preparatory phase for rapid germination following pollination, reflecting the stronger dependence of larval development on successful flower fertilization in actively pollinated figs. More broadly, our study provides the first comparative account of pollen structural and cytophysiological dynamics on fig-wasp bodies, linking pollen cell biology to pollinator-mediated dispersal and highlighting how different pollination strategies may impose distinct selective pressures on male gametophytes. Full article

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon characterized by dysregulated mucosal immunity and progressive epithelial injury. Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, has demonstrated clinical efficacy in UC, but its therapeutic application is often constrained by adverse effects arising from systemic drug exposure. This underscores the need for advanced, site-specific delivery systems that enhance local efficacy while minimizing systemic toxicity. Here, we developed a colon-targeted natural lipid nanoparticle formulation of UPA (UPA-nLNP) to improve therapeutic performance and safety. UPA-nLNP was prepared by thin-film hydration using digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG), and phosphatidic acid (PA), mimicking the lipid composition of ginger-derived exosomal particles, and was characterized for particle size, surface charge, and encapsulation efficiency. The formulation exhibited excellent mucus-penetrating capability and was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis model in C57BL/6 mice following oral administration (5 mg/kg). Pharmacokinetic analysis demonstrated increased colonic accumulation with reduced systemic exposure compared to free UPA. Treatment with UPA-nLNP improved body weight recovery, reduced disease biomarkers, and suppressed key proinflammatory cytokines in the colon, with no evidence of systemic toxicity. This innovative strategy holds strong potential to enhance the clinical utility of JAK1 inhibitors by providing a safer and more effective therapeutic approach for ulcerative colitis. Full article

The emergence of membrane boundaries represents a decisive transition in the origin of life, yet the molecular nature of the earliest abiotic membranes remains uncertain. Existing models based on simple fatty acids, while experimentally tractable, often lack the environmental robustness required under fluctuating prebiotic conditions. Furthermore, the absence of clear pathways linking primitive amphiphiles to later phospholipid systems highlights the need for chemically continuous intermediate frameworks. Here, we explore borate-bridged amphiphile–carbohydrate conjugates as plausible intermediates between simple prebiotic surfactants and modern lipid bilayers. These conjugates arise from low-molecular-weight polyols—including glycerol, butane-1,2,3,4-tetraol, pentane-1,2,3,4,5-pentaol, and hexane-1,2,3,4,5,6-hexitol—reacting with long-chain alkyl ethers and borate species under alkaline conditions, enabling reversible coupling to ribose and other vicinal diol-containing sugars. This chemistry integrates three essential properties for early compartmentalization: hydrolytically robust ether-linked hydrophobic domains, multivalent and highly hydrated headgroups, and environmentally responsive borate coordination. Comparative physicochemical analysis suggests that single-tail alkylglycerol derivatives preferentially form micelles and interfacial films, while di- and tri-tail tetritol and pentitol conjugates favor lamellar assemblies and vesicle formation across realistic prebiotic pH and salinity ranges. Hexitol-based systems, particularly those bearing three hydrophobic chains, may act as membrane-stabilizing components that enhance rigidity and reduce permeability under extreme conditions. We propose that heterogeneous mixtures dominated by two-tail polyol diethers, supplemented by tri-tail stabilizers and surface-active alkylglycerols, could provide mechanically robust, pH-tunable, and sugar-decorated abiotic membranes. Such borate-mediated amphiphiles offer a chemically coherent framework linking carbohydrate stabilization, ether lipid persistence, and dynamic self-assembly, potentially representing a transitional stage in the evolutionary pathway from primitive amphiphilic films to biologically encoded membranes. Full article

Background: The reliable co-loading of paclitaxel (PTX) and indocyanine green (ICG) into a single lipid nanoparticle (LNP) enables synergistic antitumor delivery but remains challenging due to their distinct physicochemical properties. Methods: This study integrated COSMO-RS calculations, molecular dynamics simulations, and in vitro assays to systematically investigate the effects of lipid composition, drug modification, particle size, and solvent environment on dual-drug loading. Results: This work indicate that DMPS lipid membranes featuring highly polar headgroups and ordered bilayer structures stably bind both ICG and PTX, achieving drug-loading efficiencies (DLEs) of 7.2% and 5.6%, respectively. Carboxylation of PTX enhanced hydrogen bonding with DMPS, while alkyl chain modifications improved membrane insertion, though excessive chain length (e.g., C12) reduced stability due to increased flexibility. Increasing the LNP size from 50 nm to 250 nm raised the DLE of PTX from 4.7% to 8.1%, while sizes beyond 500 nm led to membrane destabilization. The use of 20 vol% ethanol increased total drug loading by 51% by disrupting the hydration shell of ICG and suppressing PTX aggregation; however, ethanol concentrations exceeding 40 vol% intensified drug–solvent competition and weakened membrane binding. Conclusions: This study provides a comprehensive elucidation of the multifactorial regulatory mechanisms underlying dual-drug loading in LNPs, offering a theoretical basis for the rational design of efficient co-delivery systems. Full article

Background/Objectives: Beeswax, a complex natural secretion primarily derived from Apis mellifera and Apis cerana, has evolved from an ancient remedy into a multifunctional excipient and bioactive material in modern pharmaceutical sciences. This review evaluates its physicochemical properties, pharmaceutical applications, and emerging biomedical potential, while addressing current quality and regulatory challenges. Methods: A narrative review was conducted by analyzing literature on the chemical composition, functional properties, conventional uses, advanced drug delivery applications, pharmacological activities, and quality control of beeswax, emphasizing structural characteristics, formulation roles, and integration into innovative delivery technologies. Results: Beeswax is a lipid-based matrix composed of over 300 constituents, including wax esters, hydrocarbons, and free fatty acids, conferring thermoplasticity, biocompatibility, and structural stability. Traditionally, it functions as a stiffening agent, viscosity modifier, and emulsion stabilizer in topical formulations, forming an occlusive barrier that enhances skin hydration. In advanced systems, it serves as a solid lipid matrix in nanostructured lipid carriers (NLCs), microspheres, and 3D-printed tablets, enabling controlled drug release and improved bioavailability of lipophilic compounds. It also exhibits antimicrobial, anti-inflammatory, and wound-healing activities, while beeswax-derived policosanols show potential cardiovascular and gastroprotective benefits. However, concerns regarding paraffin adulteration and pesticide contamination highlight the need for stringent analytical and regulatory oversight. Conclusions: With rigorous quality control and sustainable sourcing, beeswax remains a versatile, eco-friendly material bridging traditional medicine and advanced pharmaceutical innovation. Full article

Water is fundamental to structural integrity, stability, and functional properties of food systems, biomaterials, and biobased industries. The dynamics of hydration, including hydrogen bonding, hydration shell formation, plasticization, and phase transitions, dictate molecular behavior and exert broad influence on energy consumption, shelf life, biodegradability, and resource efficiency. However, the nonlinear and multiscale characteristics of hydration have constrained the predictive capabilities of conventional empirical methods. This study introduces a comprehensive framework that integrates foundational hydration science with advanced computational intelligence to model, predict, and optimize hydration-driven phenomena across diverse biopolymer classes. Leveraging classical insights into carbohydrate stereochemistry, protein hydrophobic hydration, and phospholipid-bound water, we demonstrate how computational approaches can reduce resource use in bioprocessing by 30–50% and optimize drying curves to lower energy consumption by 25%. By establishing hydration as a strategic design parameter, this work charts a pathway toward a resilient and sustainable economy where predictive error rates for hydration dynamics are significantly minimized through data-driven calibration. Full article

Glutathione (GSH) is a central regulator of redox homeostasis, melanogenesis, and cellular repair, and has gained increasing attention in dermatology for its potential roles in skin brightening, anti-aging, and tissue regeneration. This systematic review evaluated molecular, clinical, and translational evidence of glutathione’s applications and safety across different delivery modalities. The review followed PRISMA guidelines and included studies published between 2000 and 2025. A total of 194 studies met the inclusion criteria, evaluating the effectiveness of glutathione in esthetic dermatology and regenerative medicine. Topical and oral glutathione demonstrated favorable effects on pigmentation, skin brightness, hydration, and oxidative stress markers. Injectable glutathione increases systemic levels rapidly, but is associated with short-lasting effects and potential safety concerns. Glutathione S-transferases facilitate the conjugation of glutathione to electrophilic xenobiotics, thereby protecting proteins and nucleic acids from electrophile-induced damage. Glutathione Peroxidase employs GSH as an electron donor to reduce hydrogen peroxide and lipid hydroperoxides, thus protecting membrane lipids, mitochondrial membranes, and DNA from oxidative damage. Glutathione facilitates the regeneration of other antioxidants, such as vitamin C and vitamin E, through redox cycling. A consistent correlation exists between reduced GSH levels and neuronal dysfunction. Elevated GSH levels enhance cellular resistance to oxidative stress and reduce apoptotic signaling. GSH plays a pivotal role in cutaneous aging and tissue repair through redox regulation, mitochondrial protection, and the modulation of inflammatory and extracellular matrix pathways. To elucidate the clinical significance of glutathione, future research should focus on conducting randomized controlled trials, developing standardized formulations, and performing long-term safety assessments. Full article