Search Results (19,668)

Background: Trans-resveratrol (3,5,4′-trihydroxystilbene) is a natural polyphenolic antioxidant widely used in anti-aging dermocosmetics for its strong radical-scavenging capacity and its activation of cell-protective pathways such as sirtuin 1 (SIRT1). However, its poor aqueous solubility, photochemical lability, and low bioavailability limit its incorporation into topical formulations and its delivery into the skin. Objective: In this study, ethosomal nanocarriers were designed as a phospholipid–ethanol vesicular system to solubilize, stabilize, and control the release of trans-resveratrol for dermocosmetic applications. Microfluidization is not a commonly used method; however, circulating the formulation through the interaction chamber under optimized pressure can produce ethosomes with desirable colloidal stability by this simple process. Methods: Resveratrol-loaded ethosomes were prepared with synthetic phosphatidylcholine (Lipoid P75), ethanol, and vitamin E. Microfluidization was optimized by varying the number of high-pressure homogenization cycles and the applied pressure. Vesicle size, size distribution and distribution uniformity, zeta potential, pH, conductivity, density, and long-term stability were monitored for up to 180 days; morphology was examined by cryogenic scanning electron microscopy (cryo-SEM) and molecular compatibility by Fourier-transform infrared (FTIR) spectroscopy. A trans-resveratrol high-performance liquid chromatography (HPLC) assay was developed and validated according to International Council for Harmonisation (ICH) Q2 guidelines for quantitative analysis. Encapsulation efficiency was determined by HPLC after ultracentrifugation, cytotoxicity was assessed in human keratinocytes (HaCaT), and in vitro release was evaluated using Franz diffusion cells with two different membranes. Results: All ethosome formulations yielded a nanoscale size distribution (median diameter around 190 nm for loaded and around 90 nm for unloaded) and good colloidal stability, with absolute zeta potentials above the 30 mV threshold at early time points and a skin-compatible pH (around 6.5). The optimized formulation (T16; 1.5% w/w trans-resveratrol, 5% w/w phosphatidylcholine (Lipoid P75), 0.3% w/w vitamin E and 30% w/w ethanol, processed with seven microfluidization cycles) achieved a high encapsulation efficiency (EE) of 95.5% on day 1. 84.2% EE was retained after 180 days, consistent with strong partitioning of the lipophilic active into the ethanol–phospholipid bilayer. FTIR confirmed preservation of the phospholipid bilayer and indicated non-covalent loading, with the resveratrol bands largely masked by the dominant lipid signals. Cryogenic Scanning Electron Microscopy (Cryo-SEM) confirmed near-spherical vesicles with narrow size distribution. In vitro release showed a sustained, controlled release profile relative to a 1.5% w/w resveratrol solution. Slower diffusion across the skin-mimicking Strat-M membrane was observed compared to cellulose acetate membrane. Conclusions: Optimized trans-resveratrol-loaded ethosomes represent a stable, efficient vesicular system enabling formulation stability and controlled topical release. The antioxidant and photoprotective efficacy of the loaded system was not assessed in this study and is identified as a topic for future work. Full article

INPP5D, which encodes Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1), has emerged as an Alzheimer’s disease (AD)-associated gene with strong links to microglial biology. As a hematopoietic-enriched lipid phosphatase, SHIP1 converts phosphatidylinositol-3,4,5-trisphosphate to phosphatidylinositol-3,4-bisphosphate, thereby regulating phosphoinositide-dependent receptor signaling, membrane remodeling, phagocytosis, vesicle trafficking, and inflammatory responses. In AD, microglia are chronically exposed to amyloid-β, lipid-rich debris, damaged synapses, complement-tagged structures, and inflammatory mediators. These substrates require coordinated uptake, endolysosomal processing, autophagic adaptation, and controlled inflammatory output. Current data place INPP5D/SHIP1 at a step after receptor engagement, where microglial uptake must be coupled to vesicular routing and lysosomal degradation. When this coupling fails, engulfed amyloid, lipid debris, or synaptic material may accumulate in stressed endolysosomal compartments, promoting defective autophagy, NLRP3 inflammasome activation, and sustained cytokine release. Although current data support a primarily microglial or myeloid-centered role for INPP5D in the brain, altered microglial states may secondarily affect the neurovascular unit through cytokine release, complement activation, oxidative stress, and impaired amyloid or lipid clearance. This review summarizes the molecular function of INPP5D/SHIP1 in AD-related microglial signaling and discusses its implications for phagocytosis, endolysosomal stress, inflammasome activation, therapeutic targeting, and microglia–vascular communication. Full article

Background: The coagulation cascade depends on the active participation of several elements present in the blood as well as signals arising from the endothelial cells. A platelet plug is a temporary, fast-response seal formed by platelets at the site of a damaged blood vessel to initiate hemostasis. Among the changes platelets undergo is the degranulation step. Platelet degranulation results in the release of substances like ADP, serotonin, fibrinogen, and zinc. Currently, zinc’s targets are unknown. Methods: Platelet-to-platelet aggregation relies on specific surface receptors and plasma bridge proteins. Such mechanistic elements have been extensively studied (i.e., αIIbβ3 integrin). In this work, using platelet aggregation methods and recombinant proteins, we will expand the repertoire of proteins relevant to platelet plug formation. Particularly, size-exclusion chromatography (SEC), surface plasmon resonance (SPR), and transmission electron microscopy (TEM) were mainly used. Using 1 mM zinc and 10 µM ADP, we evaluated platelet aggregation and proteins responsible for this aggregation’s behavior in response to zinc release from platelets’ granules upon activation. SPR provided results to evaluate the affinity of our target proteins on the surface of platelets when influenced by the increase in zinc after degranulation. Results: In the present work, we provide evidence that the high local concentration of zinc is intended to target junctional adhesion molecule A (JAM-A), which remains inactive (inhibiting cell-adhesion and cytoskeleton dynamics) when coagulation is not needed, and platelets move through the bloodstream as single units. Zinc-activated JAM-A leads the platelets to aggregate. Our experimentation includes work with platelets and a synthetic biology small peptide to quench the effects of zinc. Conclusions: JAM-A interacts with zinc to aid in the formation of the platelet plug. This interaction activates the cell-adhesion and cytoskeleton dynamics functions of JAM-A. We suggest that further exploring this mechanism of zinc-activated JAM-A can be advantageous for understanding hemostasis, its role in antithrombotic therapy, coagulation inhibition, or thrombosis prevention. Full article

Quercetin (QUE) and resveratrol (RES) have complementary bioactivities but limited aqueous solubility and oral bioavailability. This study developed dual-loaded quercetin–resveratrol niosomes (QR-NIOs) for incorporation into hummus and screened quercetin:resveratrol molar ratios using antioxidant, erythroprotective, and enzyme-inhibition assays. The 50:50 formulation showed the broadest activity profile and produced vesicles with 90.63 ± 3.63% overall encapsulation efficiency, 149 ± 13 nm diameter, 0.21 ± 0.02 polydispersity index, and −34 ± 2 mV ζ-potential. After 24 h, dialysis passage was 51.63%, compared with 80.35% for the unencapsulated mixture. Following simulated intestinal digestion, enriched hummus yielded 5.8 milligrams of gallic acid equivalents per gram of dry weight (mg GAE/g D.W.) and 4.7 milligrams of quercetin equivalents per gram of dry weight (mg QE/g D.W.) in the dialyzable phenolic and flavonoid fractions, respectively, exceeding both controls while retaining antioxidant and enzyme-inhibitory activities. Over 28 days at 4 °C, microbial counts remained below detection limits and the tested pathogens were absent. Overall acceptability (8.23/9) did not differ significantly from commercial hummus. QR-NIO-enriched hummus represents a sensory-compatible functional-food prototype with sustained apparent release and increased intestinal recovery of assay-reactive phenolic and flavonoid compounds; compound-specific and in vivo validation remains necessary. Full article

Background/Objectives: Elderflower (Sambucus nigra L.) extract is a rich source of bioactive compounds with promising metabolic and gut health benefits. This study aimed to develop high-quality microencapsulates and evaluate the effects of inulin and polydextrose, used individually or in combination, on their stability, bioactivity, technological performance, and functional properties. Methods: Spray-drying was employed to produce four powder formulations: extract without a carrier addition, extract with 20% inulin or polydextrose addition, and extract with a combination of 10% inulin and 10% polydextrose. The resulting microparticles were characterized by their technological properties, such as powder yield, moisture content, bulk density, and tapped density. Fourier transform infrared spectroscopy, particle size distribution, and differential scanning calorimetry were used to define their physicochemical properties, while biological activities were evaluated using in vitro assays. Results: Carrier composition substantially influenced particle size, with inulin producing the smallest and most narrowly distributed particles. Incorporation of the extract into carbohydrate matrices promoted amorphous structure formation and enhanced thermal stability, while increasing rutin solubility by nearly 50-fold compared with its reported aqueous solubility. The extract’s biological activity was associated with its high polyphenol content, particularly chlorogenic acid and rutin, while microencapsulation effectively preserved the phenolic profile during storage. In addition to displaying potent DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging capacity and α-glucosidase inhibitory potential, the developed formulations exerted biological functionality on inhibiting Gram-positive bacteria and yeasts while fostering the growth of probiotic Lactobacillus strains. Formulations containing inulin, alone or combined with polydextrose, demonstrated the most promising overall biological potential. Conclusions: Inulin and polydextrose demonstrated dual functionality as carriers by protecting elderflower bioactives while enhancing their functional properties, highlighting the potential of the resulting microencapsulates as multifunctional ingredients for food, pharmaceutical, and nutraceutical applications. Full article

Background/Objectives: The increasing incidence of invasive fungal infections and the emergence of antifungal resistance have limited the effectiveness of conventional therapies against Candida spp. This study aimed to develop and optimize nanostructured lipid carriers (NLCs) containing fluconazole (FLC) and Riparin B (RIP) using a systematic Quality-by-Design (QbD) approach. Methods: The optimized NLCs were characterized by particle size, polydispersity index (PDI), zeta potential, DSC, and FTIR analyses. Molecular docking was used as a complementary exploratory approach to investigate possible interactions of RIP with representative components of the lipid matrix and with fungal resistance-associated proteins. Release profiles and antifungal activity against Candida spp. were also evaluated. Results: The optimized NLCs exhibited a mean particle size of 144.9 ± 2.25 nm, PDI of 0.153 ± 0.03, and zeta potential of −27.8 ± 1.81 mV. DSC and FTIR analyses supported the structural organization of the lipid matrix and the formation of an imperfect crystalline network, providing structural defects favorable for the incorporation of the active compounds. RIP exhibited more favorable predicted interactions than FLC within the specific lipid configuration evaluated, although these docking scores should not be interpreted as direct thermodynamic measurements of drug–lipid affinity or as quantitative predictors of encapsulation efficiency. Docking analyses with MdR1, CdR1, and CdR2 identified possible interactions of RIP with these resistance-associated proteins, providing a structural hypothesis that may contribute to understanding the potentiation of FLC activity. However, these computational results do not establish direct efflux-pump inhibition. Release profiles followed distinct kinetic regimes, consistent with matrix relaxation for RIP and Fickian diffusion for FLC. Although RIP alone did not exhibit relevant antifungal activity, its association with FLC potentiated FLC activity against Candida spp., while incorporation of the combination into NLCs produced a further enhancement, significantly reducing the minimum inhibitory concentration. Conclusions: These findings indicate that the optimized NLC platform can enhance the antifungal performance of the FLC–RIP combination and provide a formulation framework for further investigation of this co-delivery strategy. Full article

Atherosclerosis is an age-related immune-metabolic disease in which lipid retention, endothelial dysfunction, innate immune activation, and vascular remodeling interact over decades. In older adults, inflammaging, mitochondrial dysfunction, defective autophagy/mitophagy, and cellular senescence may lower the threshold for persistent inflammasome activation in the vascular wall. The NLR family pyrin domain containing 3 (NLRP3) inflammasome and interleukin-1β (IL-1β) are central to this process because they convert sterile danger signals, including cholesterol crystals, oxidized lipids, mitochondrial stress, and disturbed flow, into caspase-1 activation, IL-1β and interleukin-18 (IL-18) maturation, pyroptosis, endothelial dysfunction, macrophage activation, and plaque destabilization. Clinical proof-of-concept from IL-1β blockade supports inflammatory targeting in atherosclerotic cardiovascular disease, but direct cytokine inhibition leaves upstream inflammasome-prone states insufficiently addressed. This narrative review synthesizes evidence published from 2010 to 2026, together with older landmark studies, on mechanistic, translational, and clinical links between the NLRP3/IL-1β axis and age-related atherosclerosis. Traditional Chinese medicine-derived formulas and isolated natural compounds are considered because they may modulate upstream priming, mitochondrial reactive oxygen species, autophagy, lipid handling, macrophage polarization, endothelial pyroptosis, and inflammasome-associated cytokine release. However, most data remain preclinical, and translation requires stronger causal validation, chemical standardization, pharmacokinetic characterization, age-relevant models, and systematic safety assessment. Full article

The repair of critical bone defects remains a substantial clinical challenge. A regenerative material must support osteogenesis, provide appropriate mechanical function, and degrade at a rate compatible with tissue formation. Hydroxyapatite (HA) is osteoconductive and chemically similar to bone mineral, but its brittleness and slow resorption limit its use as a stand-alone load-bearing material. Silsesquioxanes, particularly polyhedral oligomeric silsesquioxanes (POSS), provide molecularly defined silicon–oxygen frameworks with modifiable organic substituents. These can be incorporated as fillers or covalent network components. This review critically evaluates silsesquioxane-based biomaterials for bone regeneration. It distinguishes direct evidence from HA-containing systems from mechanistic analogues. These analogues include silicate-substituted HA, bioactive glass, dental POSS composites, and related polymer–POSS materials. Sol–gel processing, in situ mineralisation, particle incorporation, surface grafting, and network formation are assessed in relation to interfacial bonding, apatite nucleation, mechanical behaviour, and degradation. Current evidence indicates that reinforcement depends on cage functionality, dispersion, loading, matrix chemistry, and interfacial integration. Direct evidence that implanted HA–POSS systems release orthosilicic acid at biologically active concentrations remains unavailable. Cross-system comparisons further show that reported mechanical values cannot be ranked without accounting for physical form, porosity, test mode, and environmental conditions. The principal translational barriers are (i) the scarcity of load-bearing in vivo studies, (ii) uncertain degradation-product fate, and (iii) sterilisation sensitivity in some POSS-modified polymers. Further barriers are (iv) limited manufacturing standardisation and (v) the absence of clinically validated HA–POSS implants. The most defensible rationale for these hybrids is therefore their capacity for multifunctional interfacial design rather than universal mechanical superiority. Full article

Managing endangered wildlife in pre-release or semi-wild training programs requires an understanding of how animals balance strict energetic constraints against environmental health risks. We investigated the behavioral and spatial coping mechanisms of giant pandas (Ailuropoda melanoleuca) during semi-wild adaptation training exposed to intense seasonal tick (Ixodes ovatus) parasitism. Integrating high-resolution 3D-GPS telemetry, fine-scale microhabitat architecture mapping, and longitudinal daily tick counts, we evaluated the relative efficacy of behavioral hypoactivity versus microhabitat selection using Generalized Estimating Equations (GEE). During the high-risk summer season, individuals exhibited pronounced baseline behavioral suppression. However, GEE models revealed that fine-scale microhabitat selection—rather than localized movement reduction—was the primary determinant of parasite avoidance. Actively shifting to higher-elevation microhabitats with minimal leaf litter and dense bamboo coverage significantly minimized daily tick burdens. Conversely, remaining sedentary within low-elevation, thick-litter zones yielded the highest predicted parasite loads. These findings demonstrate that physical stillness alone is insufficient to mitigate ectoparasite exposure without access to structural habitat refugia. For conservation and reintroduction programs, providing structurally complex, topographically heterogeneous enclosures is essential. Ensuring access to natural altitudinal gradients empowers managed herbivores to autonomously regulate parasitological risks, thereby enhancing pre-release animal welfare and health. Full article

Hydrothermal pretreatment is routinely judged by how much organic matter it releases into solution, yet the value of that release depends on which microbial system consumes it—a premise that is rarely tested because pretreatment is almost always evaluated against a single downstream process. Two independent maize-silage batches were subjected to the same acid-free thermohydrolysis protocol with explosive decompression under conventional and microwave heating (110, 120, and 130 °C, 20 min holding time) and were then evaluated in two conversion routes of contrasting substrate specificity: mesophilic anaerobic digestion of the whole slurry, measured as cumulative methane yield at day 14 across the full temperature matrix, and alcoholic fermentation of the clarified hydrolysate by Saccharomyces cerevisiae KKP 669, applied to the two extreme temperatures only. The two routes responded in opposite directions. Temperature raised the cumulative methane yield from 99 to 241–270 NmL CH₄ g⁻¹ volatile solids (VS), with little further gain above 120 °C, while the same protocol reduced fermentative activity by up to 61%. Heating mode had no detectable effect on methane yield: two-way analysis of variance attributed 64% of the variance to temperature (p = 0.001) and 1.7% to heating mode (p = 0.446). Since the same reactor and feedstock gave a clear microwave advantage when an acid catalyst was present, this is consistent with, though it does not by itself prove, a catalyst-dependent heating-mode effect. Microwave heating nevertheless cut the energy input almost fourfold by reaching temperature three to four times faster, bringing the incremental balance close to break-even. Furanic by-products were unlikely to account for the suppression of the yeast, remaining two to three orders of magnitude below reported inhibitory concentrations; the suppression instead tracked the titratable weak-acid load, which rose from 2.0 to 8.8 g acetic acid equivalents L⁻¹ (r = −0.984). Acetic acid is simultaneously an inhibitor of yeast and a direct precursor of methane, so one protocol plausibly released compounds acting as substrate for one route and as toxicant for the other. Solubilisation indices are therefore route-specific and unreliable as general measures of pretreatment effectiveness. Full article

Bacterial-infected skin wounds, especially those caused by drug-resistant pathogens accompanied by persistent inflammation, remain a major clinical therapeutic challenge. Rising antimicrobial resistance compromises the therapeutic effect of conventional single-agent antibiotics, creating an urgent demand for novel wound therapeutics that integrate bactericidal potency, immunomodulation and tissue regeneration capacity. In this work, an injectable multifunctional chitosan-based hydrogel (C@MC) was developed, which simultaneously incorporates metformin hydrochloride (as a potential antibiotic adjuvant) and cefazolin sodium (as a β-lactam class antibacterial drug). The optimized C@MC possesses interconnected three-dimensional pores with an initial storage modulus of ~0.83 kPa (C@MC₃₆₀), featuring desirable mechanical strength, injectability, tissue adhesion and dual pH/glucose-responsive sustained drug release. In vitro evaluations revealed the dose-dependent bactericidal activity of C@MC against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and New Delhi metallo-β-lactamase-1-producing E. coli (NDM-1 E. coli, resistant bacteria). The highest drug-laden group nearly eliminated all wound bacteria in vitro. It scavenged reactive oxygen species (ROS) to lower cellular MDA levels and suppress pro-inflammatory TNF-α and IL-6 in LPS-stimulated RAW 264.7 macrophages. In full-thickness mouse wounds infected with NDM-1 E. coli, C@MC₃₆₀ achieved nearly complete wound closure, with only a 4.2% residual wound area on day 14, accompanied by suppressed inflammatory infiltration and accelerated wound regeneration. This dual-drug hydrogel integrates antibiotic potentiation, anti-inflammation and antioxidation, providing an intervention regimen for skin wounds infected with drug-resistant bacteria. Full article

The increasing demand for sustainable agricultural practices has intensified the search for biobased alternatives to synthetic agrochemicals. In this context, marine macroalgae, particularly brown algae (Phaeophyceae), represent a largely underexplored reservoir of structurally diverse secondary metabolites with significant agrochemical potential. Among these, phlorotannins and sulfated polysaccharides such as fucoidans stand out because of their multifunctional biological activities. These compounds exhibit direct effects against phytopathogens and agricultural pests through mechanisms such as enzyme inhibition, disruption of cellular and midgut homeostasis, and interference with key metabolic pathways while also acting as elicitors of plant defense by activating systemic resistance responses. This review critically examines the structural diversity of phlorotannins and fucans from Phaeophyceae, correlating their molecular features with their reported biological activities and modes of action relevant to crop protection. Particular emphasis is placed on the chemical vulnerability of these metabolites under field conditions, where photodegradation, oxidative stress, and limited bioavailability restrict their practical application. Advances in green extraction technologies—such as ultrasound-assisted, microwave-assisted, and supercritical fluid extraction—are discussed as essential tools for preserving structural integrity and bioactivity. In parallel, state-of-the-art delivery systems, including nanoencapsulation using biopolymers such as alginate and chitosan, are highlighted as effective strategies to enhance stability, controlled release, and environmental persistence. Finally, the review addresses critical challenges related to the extraction of standardization, formulation scalability, and regulatory frameworks that currently limit the commercial adoption of marine-derived agrochemicals. By integrating metabolic diversity, green chemistry, and advanced formulation technologies, Phaeophyceae-derived metabolites have emerged as promising leads for the development of innovative, low-impact agrochemicals that are compatible with integrated best management strategies and the principles of blue chemistry. Full article

Crystal (Cry) toxins produced by Bacillus thuringiensis are highly specific insecticidal proteins that are widely used as biological insecticides and function through proteolytic activation in insect midguts, which generates a three-domain toxic core responsible for membrane disruption as well as cleaved N- and C-terminal domains. While the structure and function of this core have been extensively characterized, the fate of the cleaved C-terminal region remains poorly understood. Amyloids are protein fibrils with a characteristic cross-β structure that participate in a wide range of functions in bacteria. Here, using bioinformatic approaches, we demonstrated that the C-terminal domains of Cry are rich in potentially amyloidogenic regions. We investigated the aggregation behavior of C-terminal domains from Cry1Ea11 and Cry1Ab12 proteins using a combination of biochemical and structural approaches. We found that the C-terminal domains of Cry1Ea11 and Cry1Ab12 undergo self-assembly in vitro, forming aggregates with fibrillar morphology. These assemblies bind amyloid-associated dyes, exhibit partial resistance to ionic detergents and proteolytic digestion, and display X-ray diffraction patterns confirming their amyloid properties. Functional assessment in insect cells showed that although these amyloids do not induce detectable cytotoxicity, amyloids of the C-terminal domains of Cry1Ea11 alter the readouts of the MTT assay in a manner consistent with previously described amyloid-associated effects on cellular formazan handling. Together, our findings demonstrate that the C-terminal domains of Cry toxins, which are released in the insect midgut as a result of proteolytic cleavage, are able to form bona fide amyloids that affect the metabolism of insect cells. Full article

Melanoma remains one of the most aggressive forms of skin cancer, characterized by high metastatic potential and risks of tissue trauma and post-surgical recurrence, with limited therapeutic options currently available. While conventional monotherapies often fail to provide comprehensive and efficient treatment, nanoparticle-functionalized hydrogel platforms have emerged as promising multifunctional systems for localized combination cancer therapy, capable of integrating multiple therapeutic modalities, such as chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT), tissue recovery support, antibacterial activity, and image-guided treatment into a single biomaterial. This review examines stimulus-responsive hydrogels based on the anionic polysaccharides carboxymethylcellulose (CMC) and hyaluronic acid (HA), conjugated with nanoparticles for melanoma theranostic applications. It evaluates their design, synergistic mechanisms, and therapeutic potential. It considers how combining CMC and HA overcomes the limitations of individual polymers, such as poor mechanical integrity and rapid degradation, and enhances key functionalities, particularly cell targeting and specificity. It also analyzes how incorporating functional nanoparticles can enable on-demand drug release, diagnostic imaging, immune microenvironment remodeling, and combined phototherapy (PTT/PDT). While HA-based nanotheranostic systems are widely documented, the potential of CMC in melanoma treatment remains largely untapped, despite its proven success in tissue engineering and wound management. Most significantly, the literature currently lacks any bio-nanohybrid platform that integrates CMC and HA, driven by functional hybrid nanoparticles, for targeted melanoma therapy. By identifying this critical gap, this review proposes new research avenues for designing these unified, multifunctional platforms as a highly promising strategy for cutaneous melanoma management. Full article

Extracellular vesicles (EVs) are increasingly recognized as mediators of intercellular communication and as potential therapeutic and diagnostic platforms. In the ocular surface and anterior segment, EVs are released by epithelial, stromal, endothelial, immune, and aqueous outflow-related cells and are also detectable in tears and aqueous humor. Experimental studies suggest that EVs may promote corneal epithelial repair, modulate local immune responses, reduce stromal fibrosis, and participate in extracellular matrix regulation within the trabecular meshwork. In parallel, mesenchymal stromal cell-derived EVs are being investigated as cell-free therapeutics, while engineered EVs and EV–lipid hybrid systems may facilitate the delivery of nucleic acids and other therapeutic cargo to anterior segment tissues. Tear- and aqueous humor-derived EV preparations have also yielded candidate molecular signatures for ocular surface disease, glaucoma, and selected systemic disorders. However, much of the current evidence remains preclinical or exploratory. Reported effects are frequently based on conditioned medium, EV-enriched fractions, or incompletely characterized preparations, making it difficult to distinguish EV-specific activity from that of the broader secretome. Biomarker studies are additionally limited by small cohorts, low sample volumes, non-vesicular contaminants, and methodological heterogeneity. This review summarizes the biological roles, therapeutic applications, drug-delivery potential, and diagnostic use of EVs in anterior segment medicine. Particular emphasis is placed on the strength of EV-specific evidence, the limitations of extrapolating from non-ocular models, and the methodological, manufacturing, and regulatory requirements for clinical translation. EVs represent a promising interface between anterior segment biology, precision diagnosis, and targeted therapy, but rigorous characterization and comparative validation remain essential. Full article