Search Results (368)

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

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

Life demonstrates remarkable homochirality of its major building blocks: nucleic acids, amino acids, sugars, and phospholipids. Phospholipid bilayer vesicles (liposomes) are formed at the water/air interface from Langmuir layers and contain ribose, a constituent of primordial water. Although the primordial ribose was initially racemic, life, as we know it, is homochiral, with d-ribose and its derivatives as the predominant forms. The phospholipid membrane’s permeability to d-ribose, together with ribose’s interaction with the bilayer’s charged phosphate groups, leads to ribose phosphorylation, yielding d-ribose-5-phosphate. Once inside, the d-ribose-5-phosphate molecules cannot cross the membrane. A similar path also exists for l-ribose, but with a lower rate. Therefore, overall, this process is enantioselective, favoring the buildup of d-ribose over l-ribose. Through liposome fusion, fission, and self-replication, this eventually leads to the Darwinian evolution of these structures and to the conversion of d-ribose-5-phosphate into complex functional molecules, such as ribozymes and RNA, and eventually into DNA, all of which inherit d-ribose’s chirality. Full article

This study aims to develop and systematically evaluate a new lipid-based formulation of blueberry anthocyanins, which can accelerate the healing effect of the cornea. The study first successfully screened and optimized the formulation and preparation process for blueberry anthocyanin liposomes. Characterization via transmission electron microscopy and dynamic light scattering revealed uniformly distributed, near-spherical liposomes with distinct phospholipid bilayers. Key physicochemical parameters—particle size, zeta potential, encapsulation efficiency, and drug loading capacity—all met formulation standards. In vivo pharmacodynamic experiments demonstrated that topical administration of blueberry anthocyanin liposomes significantly accelerated the repair process and effectively mitigated depressional damage to the corneal epithelium in a New Zealand white rabbit corneal injury model induced by 10.6 μm mid-infrared CO₂ laser. In summary, the blueberry anthocyanin liposomes successfully prepared in this study exhibit excellent performance, effectively enhancing drug exposure levels in vivo and promoting corneal repair. This provides reliable experimental evidence for the development of plant natural active ingredients in ophthalmic treatments. 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

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

Magnesium is an essential divalent cation required for adenosine triphosphate (ATP)-dependent reactions, nucleic acid metabolism, and ribosomal stability. Bacteria depend on specialized transport systems to maintain intracellular Mg²⁺ homeostasis as it cannot freely cross the phospholipid bilayer. During infection, host nutritional immunity restricts metal availability, and magnesium limitation within the phagosome compromises bacterial metabolism and stability. This review summarizes the major bacterial magnesium transport systems and their roles in survival and pathogenicity, with an emphasis on Salmonella and extension to clinically relevant ESKAPE pathogens. We focus on the PhoPQ-regulated MgtA, MgtB, and MgtC system, in which low magnesium, acidic pH, and other host-derived signals activate PhoPQ to induce mgt gene expression. MgtA and MgtB act as high-affinity P-type ATPases, whereas MgtC promotes bacterial survival within the intramacrophage environment by inhibiting bacterial F-type ATP synthase through specific interactions with subunit a. We also discuss CorA as a conserved channel for basal Mg²⁺ uptake and MgtE as a Mg²⁺-selective channel whose gating responds to intracellular Mg²⁺ and ATP. Finally, we consider the conservation and variation in these systems across pathogenic bacteria and their potential as therapeutic targets for antimicrobial development. 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

Cyclotides are exceptionally stable plant peptides whose biological activity is widely attributed to interactions with lipid membranes, yet the molecular mechanisms underlying these interactions remain incompletely resolved. Here, we employ microsecond-scale (1 μs) all-atom molecular dynamics simulations to investigate the membrane association of the cyclotide kalata B1 with phospholipid bilayers of distinct headgroup composition, including POPC, POPE, and POPG. This extended timescale enables full bilayer equilibration and allows observation of slower peptide-induced membrane responses that are not accessible in shorter simulations. Across all systems, kalata B1 rapidly adsorbs to the membrane surface and remains predominantly surface-associated throughout the simulations, while the cyclic cystine knot motif remains structurally intact, confirming the exceptional robustness of the cyclotide fold during membrane engagement. Lipid-dependent differences arise primarily from variations in peptide orientation, conformational flexibility, and interfacial dynamics rather than deep bilayer insertion or pore formation. Zwitterionic POPC membranes favor compact, upright peptide configurations, whereas POPE and POPG bilayers promote enhanced lateral spreading and dynamic reorganization driven by hydrogen bonding and electrostatic interactions, respectively. Leaflet-resolved analyses of lipid contacts, membrane thickness, and area per lipid reveal localized, asymmetric perturbations confined to the peptide-exposed leaflet, with no evidence of sustained bilayer thinning or global destabilization. Together, these results support an interfacial, headgroup-dependent mechanism of cyclotide membrane activity and reconcile previous experimental observations. This work provides molecular-level insight into lipid selectivity and early-stage cyclotide–membrane interactions that may inform future design of cyclotide-based bioactive agents. Full article

Kaurenoic acid (KA) is an ent-kaurane diterpenoid present in several medicinal plant species and has been reported to exhibit anti-inflammatory, cytotoxic, and analgesic activity in experimental models. Despite its pharmacological profile, the development of KA as a therapeutic agent has been hindered by its unfavorable physicochemical and biopharmaceutical properties. KA is highly lipophilic and poorly soluble in water, which limits its dissolution, systemic exposure, and oral bioavailability. These limitations are common among plant-derived bioactive compounds and pose significant challenges for clinical development. Lipid-based nanocarrier systems, particularly liposomal formulations, have therefore been investigated as potential delivery strategies for improving the biopharmaceutical performance of KA. Encapsulating KA within phospholipid bilayers can improve its apparent solubility, protect it from degradation, and modify its biodistribution compared to the free compound. In this review, we discuss the pharmacological mechanisms of KA, its physicochemical properties, and the biopharmaceutical barriers to its therapeutic development. We also critically evaluate published studies on nanocarrier-based formulations, focusing on encapsulation efficiency, particle size, release properties, and pharmacokinetics (PK). Additionally, regulatory and pharmaceutical considerations relevant to lipid-based delivery of KA are addressed. Available evidence supports lipid-based nanocarriers as a promising strategy to improve preclinical development and formulation performance of poorly soluble plant bioactives such as kaurenoic acid. Although KA-loaded nanocarriers demonstrate encouraging activity in preclinical models, comprehensive pharmacokinetic and safety evaluations remain necessary before clinical development can be realistically considered. Full article

Monoenoic fatty acids (MUFAs), defined by the presence of a single carbon–carbon double bond within a long aliphatic chain, constitute a structurally diverse and ecologically significant class of lipids widely distributed in aquatic organisms. In marine and freshwater environments, MUFAs are fundamental components of membrane phospholipids and storage lipids, where mono-unsaturation modulates melting point, lipid packing, and bilayer dynamics, enabling homeoviscous adaptation to fluctuations in temperature, pressure, salinity, and oxygen availability. Positional and geometric isomerism (e.g., cis-Δ5, Δ7, Δ9, Δ11, Δ13, and trans forms) further enhances biochemical diversity, providing sensitive chemotaxonomic markers and indicators of trophic transfer across food webs. In addition to common straight-chain monoenes, rare methyl-branched, cyclopropane-containing, and acetylenic derivatives occur in specialized aquatic taxa, reflecting evolutionary adaptation and ecological niche differentiation. Computational QSAR analyses suggest that monoenoic fatty acids and their unusual analogues occupy bioactivity spaces associated with lipid metabolism regulation, vascular and inflammatory modulation, antimicrobial defense, and membrane stabilization. This review integrates structural chemistry, biosynthesis, ecological distribution, trophic dynamics, and predicted biological activity of monoenoic fatty acids in aquatic systems, highlighting their dual role as adaptive membrane constituents and as biologically active mediators linking molecular lipid architecture to hydrobiological function and environmental change. Full article

Background: Plant-derived nanovesicles (PDNVs), a class of naturally occurring nanoparticles with a phospholipid bilayer structure, have attracted significant attention in biomedicine, particularly in anti-tumor research, due to their broad source availability, low production cost, high biocompatibility, and low immunogenicity. Methods: This review systematically summarizes and analyzes the isolation methods, composition, anti-tumor mechanisms, and clinical translation potential of PDNVs based on literature retrieved from PubMed and Web of Science, with clinical trials identified and categorized using ClinicalTrials.gov. Results: Current research has made impressive progress in the application of PDNVs, both as direct therapeutic agents and as drug delivery systems. Their remarkable stability, ability to cross physiological barriers (e.g., the gastrointestinal tract and blood–brain barrier), and engineerability underpin their versatile potential. Conclusions: This review comprehensively outlines the compositional characteristics of PDNVs and explores their multi-dimensional mechanisms and application prospects as natural therapeutics and drug delivery platforms in cancer therapy. Despite challenges such as standardization in preparation, PDNVs represent a highly promising class of novel nanobiomaterials. Full article

Silica particles are promising multifunctional drug delivery platforms; however, when in contact with blood or other biological fluids, proteins rapidly adsorb to their surface, forming the protein corona that modulates their biological interactions. In this study, silica microparticles were coated with lipid bilayers using two approaches: the lipid film hydration method and the on-particle solvent-assisted lipid coating (OPSALC) technique. We investigated how phospholipids with varying charges (zwitterionic, anionic, and cationic) and membrane phase influence coating formation and protein corona adsorption. The coating coverage and aggregation were characterized by fluorescence microscopy. The lipid film hydration method enabled coating with a broad range of lipids, but was highly dependent on the membrane phase and electrostatic interactions between lipid head group and particle surface. Pure anionic coatings were not achievable with this method; however, when combining the OPSALC method with a pre-silanization step, fully anionic coatings of silica microparticles were successfully obtained. Assessment by SDS-PAGE revealed differences in protein corona profiles modulated by the lipid compositions on the particles’ coatings. Overall, this study highlights the dependence of coating formation and protein corona composition on the phospholipid coatings’ properties. Full article

Catechins are characterized by a basic structure consisting of two benzene rings and a hydropyran heterocyclic ring. In (-)-epicatechin (ECT), the substituents in C2 and C3 of the dihydropyran ring are in cis conformation, whereas in (+)-catechin (CT), they are in trans conformation. Catechins tend to interact with membrane proteins, affecting their activity and/or function and metabolic processes. In this study, the impact of CT and ECT on erythrocyte membrane and cell functions was analyzed. Surprisingly, although the two compounds have a very similar structure that differs only in the orientation of the hydroxyl group in C3, they promote different effects on anion exchange through the phospholipid bilayer and on the release of ATP from cells. Anion transport mediated by Band 3 protein is reduced in the presence of CT compared with ECT which conversely increases it, and this observation aligns with the mechanisms of action we hypothesized in silico for the two compounds. Finally, ECT causes an increase in intracellular ATP levels unlike CT, and both molecules cause a decrease in ATP released from the erythrocyte. These findings could pave the way for further studies aimed at better understanding of the potential properties and structure–activity relationships of these molecules. Full article