Search Results (926)

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Plant-derived exosome-like nanoparticles (PELNs), a subset of extracellular vesicle (EV) secreted by plant cells, have emerged as revolutionary biomaterial with broad applications in biomedicine, agriculture, and nanotechnology. Structurally, PELNs feature a phospholipid bilayer homologous to plant cell membranes, encapsulating bioactive components such as proteins, nucleic acids, lipids, and secondary metabolites. The native structure of PELNs endows them with enhanced bioavailability, reduced immunogenicity, and improved barrier penetration for precise tissue delivery. Recent studies highlight the cross-kingdom therapeutic potential of PELNs in mammals, including antitumor, anti-inflammatory, tissue repair, immunomodulation and so on. This review comprehensively summarized recent advancements in PELN research, including innovative isolation techniques, molecular characterization, their roles in drug delivery and disease therapy. We also discussed challenges in standardization, scalability, and regulatory frameworks which could provide future perspectives for translating PELNs into clinical and industrial applications. Full article

Bacterial extracellular vesicles (BEVs) are nanoscale spherical lipid bilayer structures secreted by bacteria, including outer membrane vesicles (OMVs) released by Gram-negative bacteria and membrane vesicles (MVs) produced by Gram-positive bacteria. Although the biogenesis of BEVs requires substantial energy expenditure, these vesicles provide bacteria with strategic advantages in the evolutionary interplay between pathogens and hosts. BEVs contribute to bacterial adaptation to environmental stress by remodeling membrane components, eliminating toxic substances, promoting biofilm formation, and mediating the interbacterial transfer of antibiotic resistance determinants. They can also function as decoys to protect bacteria from bacteriophage or antibiotic attack, deliver virulence factors, modulate host immune responses to facilitate bacterial colonization, and mediate interspecies competition. This review summarizes the central roles of BEVs as bacterial mediators of environmental responses, with particular emphasis on their involvement in immune regulation, environmental adaptation, and interspecies competition, thereby providing new insights into pathogen evolutionary strategies. Full article

HP1090 is a short, cationic, amphipathic peptide derived from scorpion venom and previously described as a membrane-active antiviral compound. Here, we primarily characterize the antiviral activity of HP1090 and assess whether additional antibacterial effects are consistent with membrane-disruptive properties. Chemically synthesized HP1090 exhibited dose-dependent virucidal activity against multiple enveloped viruses, including herpes simplex virus type 1 and 2 (HSV-1, HSV-2), human immunodeficiency virus type 1 (HIV-1), and Zika virus (ZIKV), with IC₅₀ values ranging from 14.7 to 56.1 µg/mL. No activity was observed against the non-enveloped human rhinovirus 14 (HRV14), suggesting strict dependence on a viral lipid envelope. Consistent with a membrane-targeting mechanism, HP1090 induced rapid and concentration-dependent permeabilization of virus-like liposomes. HP1090 also displayed antibacterial activity against selected clinically relevant pathogens in agar-based growth inhibition assays. However, antibacterial effects required substantially higher concentrations (>125 µg/mL) and varied between bacterial species, with some strains showing little or no susceptibility. Membrane permeabilization assays in Listeria monocytogenes demonstrated disruption of bacterial membrane integrity as a contributing mechanism. No cytotoxicity was observed on mammalian cell lines at effective antiviral concentrations. Together, these findings establish HP1090 as a membrane-active venom peptide and, by linking envelope-dependent viral inactivation with bacterial membrane permeabilization, support a shared biophysical mode of action relevant to the development of membrane-targeting anti-infectives. Full article

Bacterial outer membrane vesicles (OMVs) are spherical structures made up of a double layer, they are each nanostructured (20–300 nm), and they are released from all populations of Gram-negative bacteria. The purpose of this review is to synthesize a comprehensive summary of the current state of knowledge about OMV biogenesis, function in biology, and application to biomedical engineering. Using these three known biogenesis mechanisms as a basis for this review, we discuss the mechanisms of OMV biogenesis that have been described as conserved: (1) disruption of outer membrane–peptidoglycan links. (2) periplasmic stress-driven adaptive release is associated with bilayer lipid asymmetry and the use of signaling molecules. OMVs are considered to be “public goods” for the microbe, allowing for nutrient acquisition, resistance to antibiotics, and the potential for horizontal gene transfer between microbes. OMVs exhibit a different duality at the interface of the pathogen host, where the pathogenic OMV is the delivery vehicle for virulence factors and pathogen-associated molecular patterns (PAMPs) leading to host immune response, while the symbiotic OMV (e.g., those produced by Bacteroides fragilis (Bact. fragilis)) promote regulatory T cell differentiation and mucosal tolerance. The review also addresses the various techniques currently available to isolate OMVs (e.g., ultracentrifugation and size-exclusion chromatographic techniques) and presents engineered/alloying strategies (e.g., genetic modifications to tolR/msbB and surface functionalization) to enhance the viability, safety, and specificity of OMVs for biomedical delivery. Finally, the review addresses significant obstacles related to standardization, batch variation, and in vivo safety associated with synthetic or personalized therapeutics based on OMVs, providing some recommendations for future research in this area. Full article

The most recent research has demonstrated that oscillatory nano-structures found on the lumenal walls of deep cerebral veins likely contribute significantly to the regulation of the function of deep cerebral veins. The oscillatory nano-structures consist of very small, intricately organized “nanoflaps,” each consisting of a hinge element with an attached lipid bilayer architecture. These nanoflaps have distinct mechanical properties, are in close proximity to mechanically sensitive protein assemblies, and therefore it is hypothesized that the nanoflaps generate rhythmic oscillations that control the distribution of both pressure and fluid flow through the veins and also regulate the metabolic condition of the surrounding tissue. In addition, the behavior of the nanoflaps indicate that there exists a hitherto unappreciated level of venous biomechanics at the nanometer scale that regulates the hydraulic stability of the veins and may also contribute to the structural integrity of the surrounding tissues. The purpose of this review is to provide a theoretical framework for understanding the recent discoveries of the structure, oscillation and hydrodynamic effects of nanoflaps, including resonance drift, waveform irregularity, and multi-scale biomechanical interactions. Additionally, this review will present the idea that disruption of the normal oscillatory processes that occur in the nanoflaps may lead to the development of abnormal micro-environments in the early stages of neurodegenerative diseases, abnormalities of compliance, dysautonomic states, traumatic injury and micro-circulatory stress. Finally, this review will describe several pharmacological strategies that may be used to stabilize the oscillations generated by the nanometer-scale oscillatory nano-structure by modifying the torque applied to the hinge, the viscoelasticity of the membrane and the feedback pathways for mechanotransduction. Full article

Background: Cytochrome P450 3A4 (CYP3A4) is a key membrane-anchored drug-metabolizing enzyme. Its expression and purification in heterologous systems are severely hindered by low yield and detergent-induced structural inactivation. Although extracellular vesicles (EVs) provide an ideal natural lipid bilayer environment to stabilize membrane proteins, targeted loading remains challenging. The ESCRT and ALIX-binding region (EABR) of CEP55 can efficiently recruit core components of the endosomal sorting complex (ESCRT) to mediate membrane fission. Objectives: This study used the EABR motif to drive the targeted vesicular secretion of CYP3A4, thereby establishing a novel membrane protein engineering platform. Methods and Results: EABR was fused with fluorescent protein, confirming its specific mediation of vesicular secretion. Recombinant plasmids of EABR/CYP3A4 and its reverse mutant (R-EABR) were transfected into HEK293T cells. Western blot and midazolam-based metabolic assays showed that forward EABR significantly enhanced CYP3A4 expression and EV secretion, while R-EABR lost exocytosis function. EVs isolated by ultracentrifugation verified EABR’s role in recruiting ESCRT and improving CYP3A4 activity. Conclusions: Forward CEP55-EABR specifically and efficiently drives vesicular encapsulation of CYP3A4, enhancing its expression and secretion. This ESCRT-mediated strategy avoids destructive purification, provides a stable lipid-rich bioreactor for CYP3A4, and has great translational potential in high-throughput in vitro drug metabolism and screening platforms. Full article

The cell wall (CW) of Mucoromycota has a unique chitin/chitosan complex, unlike chitin/glucan complex in Ascomycota. Under cell wall stress (CWS), induced by azo dyes, ascomycetes increase the amount of CW chitin. This study analyzes the response of Mucor flavus to CWS, induced by Congo red and Calcofluor white. It was found that azo dyes significantly reduced the biomass yield and inhibited apical growth and branching but did not lead to an increase in the amount of CW chitin/chitosan, neutral polysacchrides and cytosol osmolytes. Non-bilayer phosphatidic acids and phosphatidylethanolamines dominated in the control membrane lipids, but the proportion of bilayer phosphatidylcholines did not exceed 5%. Under CWS, the proportion of phosphatidic acids increased, while the proportion of phosphatidylethanolamines decreased and the degree of unsaturation of phospholipids increased. Storage lipids in the control were represented by mono-, di- and triacylglycerides and free fatty acids. Under CWS, the proportion of diacylglycerides increased significantly, while the proportion of triacylglycerides decreased. Thus, the CWS response of M. flavus consisted of significant changes in growth and the composition of membrane and storage lipids, but the amount of CW chitin/chitosan and cytosol osmolytes did not increase, which is different from the response of ascomycetes. Full article

Xanthophylls are oxygenated carotenoids widely distributed in photosynthetic microorganisms, plants, algae, and certain invertebrates, where they function as key photoprotective and antioxidant pigments. Among them, xanthophylls containing vicinal 1,2-diol moieties exhibit unique chemical reactivity that enables reversible coordination with boron species naturally present in marine and terrestrial environments. The formation of cyclic borate esters between boron and diol-containing xanthophylls induces structural and electronic modifications that may enhance pigment stability and functional performance. Emerging evidence suggests that boron–xanthophyll complexes display improved resistance to photooxidative degradation, enhanced singlet oxygen quenching capacity, and increased radical-scavenging activity compared with their uncomplexed counterparts. In addition, boron coordination can influence molecular conformation, polarity, and supramolecular organization within lipid bilayers, thereby promoting membrane stabilization under conditions of high light exposure and oxidative stress. Together, these effects indicate a cooperative role of boron complexation in amplifying the intrinsic photoprotective and antioxidant properties of xanthophylls. A deeper understanding of the structural basis and biological implications of boron–xanthophyll interactions may provide new insights into adaptive stress tolerance in marine and photosynthetic organisms, as well as guide the development of advanced photoprotective systems for biomedical and technological applications. Full article

Bipolar cancellation (BPC) is an efficiency-limiting phenomenon in bipolar nanosecond pulsed electric field (nsPEF) exposures, in which the second, opposite-polarity phase reduces or partially reverses the electroporation induced by the first phase. Nisin, a cationic antibiotic peptide, has been reported to interact with lipid membranes in bacterial systems and artificial bilayer models, where it may contribute to membrane destabilization and increased permeability during pulsed electric field exposure. This study investigated whether nisin may enhance the efficacy of bleomycin electrochemotherapy (ECT) in the presence of bipolar nanosecond pulses, which are typically associated with pronounced BPC effects. Pulsed electric field (PEF) parameters and drug concentrations were selected based on preliminary viability and Yo-Pro-1 uptake experiments in CLS-354 human squamous cell carcinoma cells. To evaluate the effect of nisin, cell viability and membrane permeabilization were assessed following exposure to 300 ns pulses across a range of bipolar PEF protocols, with or without nisin, while identical unipolar pulses were used for comparison. Nisin (50 µg/mL) increased membrane permeabilization across the tested range of field amplitudes (9–15 kV/cm) and burst repetition frequencies (0.1–1.66 MHz). The presence of nisin was also associated with increased efficacy of bleomycin-based ECT under both unipolar and symmetrical bipolar PEF conditions. Under the optimized parameters tested (13 kV/cm; 150 pulses of 300 ns at 1.66 MHz), bipolar nsPEFs in combination with nisin reached levels of efficacy comparable to those observed with unipolar waveforms, suggesting a potential attenuation of bipolar cancellation effects. Full article

Bacterial membrane vesicles (BMVs), encompassing outer membrane vesicles (OMVs) released from Gram-negative bacteria and extracellular vesicles (EVs) released from Gram-positive bacteria, have emerged as promising vaccine platforms owing to their intrinsic immunostimulatory properties and capacity to deliver a wide range of antigens. Although conventional vaccines effectively prevent infectious diseases, their long-term efficacy is often limited by antigenic variation and reliance on a restricted number of licensed adjuvants. BMVs, as self-adjuvanting systems, enable both antigen delivery and innate immune activation. BMVs are nanoscale lipid bilayer structures enriched with pathogen-associated molecular patterns (PAMPs), facilitating their recognition and uptake by antigen-presenting cells. This leads to the activation of pattern recognition receptors and the induction of pro-inflammatory cytokines, type I interferons, and adaptive immune responses, including antibody production and Th1- and Th17-biased cellular immunity. Recent studies highlight the versatility of BMVs as vaccine platforms across bacterial, fungal, and viral infection models. BMVs induce protective immunity by promoting both systemic and mucosal immune responses, thereby reducing bacterial burden and limiting pathogen colonization across diverse infection models. These properties have supported their application in viral vaccine development, including influenza and SARS-CoV-2, with the potential to enhance mucosal immunity. Despite these advantages, challenges remain in standardization, safety, and antigen-loading efficiency. Engineered BMVs incorporating protein or mRNA antigens may further enhance antigen presentation and CD8⁺ T cell responses. This review summarizes the biological features, immunological mechanisms, and future potential of BMVs in vaccine development. Full article

Micro- and nanoplastics (MNPs) are increasingly recognized as frequent environmental pollutants with growing evidence of tissue-specific lipid disruption in exposed organisms. MNP exposure is unavoidable and has attracted global attention due to its potential public health and ecological security risks. Unlike earlier studies that emphasize oxidative stress and inflammation, recent findings show that lipids are among the earliest and most sensitive molecular targets of MNP exposure. Lipidomics investigations across animal models reveal consistent patterns of lipidome remodeling, including altered phospholipid composition, disrupted sphingolipid balance, increased neutral-lipid storage, and mitochondrial lipid damage in metabolically active tissues such as the liver, kidney, lung, adipose tissue, and brain. Mechanistically, MNPs perturb membrane bilayer organization, induce MUFA and PUFA peroxidation, and destabilize lysosomal and mitochondrial function. These alterations trigger cardiolipin oxidation, ceramide accumulation, lipid droplet biogenesis, and impaired lipophagy, which collectively promote metabolic stress, energy imbalance, and neurotoxic or hepatotoxic phenotypes. Despite the growing number of tissue-specific studies, a major gap remains in understanding systemic MNP toxicity. The present review uniquely emphasizes tissue-resolved lipidomic signatures to identify convergent pathways of lipid disruption and proposes a conceptual framework, the “Lipid–Stress Axis”, to explain how localized lipidome perturbations may propagate into broader physiological dysfunction. By integrating lipidomics with metabolomics, imaging, and systems-biology approaches, we highlight key lipid-based biomarkers, mechanistic insights, and research needs essential for improving risk assessment and developing mitigation strategies against MNP-induced lipid dysregulation. Full article

Cells contain an unexpectedly large diversity of lipid molecules. Modern lipidomics studies have revealed that even a single cell type can harbor hundreds to thousands of distinct lipid species that differ in headgroup structure, acyl chain length, and degree of unsaturation. While this remarkable diversity is now well established, its biological significance remains incompletely understood. Why do cells maintain such complex lipidomes? In this review, we examine several conceptual frameworks that may help explain the origin and functional significance of lipid diversity. First, the physical properties of biological membranes impose constraints on lipid composition, as variations in lipid structure influence membrane fluidity, curvature, thickness, and phase behavior. Second, lipids can regulate membrane protein function through specific interactions and through the physical environment of the lipid bilayer. Third, lipid metabolism generates signaling molecules that participate in diverse regulatory pathways. Fourth, lipid metabolic networks continuously remodel membrane composition, producing dynamic lipidomes that can adapt to physiological conditions. Finally, evolutionary processes have shaped membrane lipid composition across different domains of life, suggesting that lipid diversity may reflect long-term adaptation to functional and environmental constraints. Taken together, these perspectives suggest that lipid diversity is unlikely to be a simple byproduct of metabolism. Instead, the cellular lipidome may emerge from the interplay of membrane biophysics, metabolic network architecture, protein regulation, and evolutionary pressures. Understanding why cells contain thousands of lipid species therefore represents an important challenge for modern cell biology and may reveal fundamental principles governing the organization of biological membranes. Full article

Oxicam derivatives, a class of nonsteroidal anti-inflammatory drugs (NSAIDs), are important scaffolds for developing biologically active compounds. In this study, arylpiperazine oxicam derivatives (PR24–PR50) were examined for membrane interactions, cytotoxic activity, cyclooxygenase inhibition, and potential binding to COX-2 protein. Membrane interactions were examined using differential scanning calorimetry (DSC) in phospholipid bilayers formed from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). All compounds altered the thermotropic properties of the lipid bilayer, showing concentration-dependent decreases in phase transition temperature, indicating incorporation to bilayer and partial disruption of lipid organization. Cytotoxicity, assessed using the MTT assay in breast cancer (MCF-7, MCF-7/DX), colorectal cancer (LOVO, LOVO/DX), and normal V79 cell lines, showed moderate effects, particularly against colorectal cancer cells. Cyclooxygenase inhibition was rather weak, with IC₅₀ values in the high micromolar range, indicating limited anti-inflammatory potential compared with reference COX inhibitors, although docking studies suggested possible interactions with the COX-2 active site. The obtained results indicate that the biological activity of the arylpiperazine oxicam derivatives is primarily associated with cytotoxicity and membrane effects rather than COX inhibition. These limitations should be considered in the design of future membrane-targeted bioactive compounds. Full article

A series of hexadecylpiperidinium surfactants containing alkyl (PMe-16, PEt-16, PBu-16), benzyl (Benz-16, 1-Benz-3-HP-16, 1-Benz-4-HP-16), and hydroxyl (3-HPMe-16, 4-HPMe-16) substituents in the ring were tested with the nematode Caenorhabditis elegans to investigate the relationship between nematocidal activity and the structural features of surfactants. It was found that increasing the hydrophobicity of the substituent in the surfactant head group reduced the nematocidal activity in the order PMe-16 > PEt-16 > PBu-16 > Benz-16. The lead compound, PMe-16, showed significantly higher activity than the commercial insecticide carbofuran, and was able to induce nearly complete nematode mortality within 24 h at a concentration of 50 μg·mL⁻¹, as well as suppress culture development at concentrations of 25–100 μg·mL⁻¹. All tested piperidinium surfactants inhibited nematode population development at 100 μg·mL⁻¹, while PMe-16 remained effective at concentrations as low as 25 μg·mL⁻¹. The membranotropic properties of the surfactants were evaluated using a turbidimetric method with dipalmitoylphosphatidylcholine (DPPC)-based liposomes as a model of biomembranes. Dynamic light scattering measurements were performed in parallel to assess changes in liposome size and zeta potential as a function of surfactant content, as well as to determine the critical concentration required to induce lipid bilayer destabilization. These results provide indirect evidence of surfactant–membrane interactions. The combinations of piperidinium surfactants and carbofuran showed pronounced synergistic effects, reducing the insecticide dose while maintaining efficacy. Synergy was evaluated using the Bliss independence model and the Highest Single Agent model. The addition of the most active surfactants (PMe-16 and 4-HPMe-16) at 6.25 μg·mL⁻¹ enabled an approximately twofold reduction in the carbofuran dose while maintaining full nematocidal activity. Full article