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Giant lipid vesicles are closed compartments consisting of semi-permeable shells, which isolate femto- to pico-liter quantities of aqueous core from the bulk. Although water permeates readily across vesicular walls, passive permeation of solutes is hindered. In this study, we show that, when subject to a hypotonic bath, giant vesicles consisting of phase separating lipid mixtures undergo osmotic relaxation exhibiting damped oscillations in phase behavior, which is synchronized with swell–burst lytic cycles: in the swelled state, osmotic pressure and elevated membrane tension due to the influx of water promote domain formation. During bursting, solute leakage through transient pores relaxes the pressure and tension, replacing the domain texture by a uniform one. This isothermal phase transition—resulting from a well-coordinated sequence of mechanochemical events—suggests a complex emergent behavior allowing synthetic vesicles produced from simple components, namely, water, osmolytes, and lipids to sense and regulate their micro-environment. All living cells are surrounded by a membrane that water can pass through. However, water often contains other molecules called solutes, and many of these cannot pass through the cell membrane. If the concentration of solutes outside the cell is, say, suddenly decreased, then water molecules will tend to move into the cell to lower the solute concentration there. This process, which is called osmosis, strives to equalize the solute concentrations inside and outside the cell. Osmosis can have dramatic consequences for cells. Animal cells need to be bathed in water to survive, but if the solute concentration outside a cell is higher than inside, the cell can lose a lot of water and die. And if the solute concentration outside is lower, then water enters the cell and it can burst. Single celled microbes use a variety of strategies to counter the movement of water by osmosis: strong cell walls prevent the cell from swelling too much, and channel proteins in the membrane can be opened to allow solutes to pass through. But it is not known how more primitive cells—cells that lived billions of years ago—might have responded to fluctuations in their environment. Oglęcka et al. have now used artificial membranes to make closed compartments called giant vesicles that mimic certain properties of cells. When giant vesicles are filled with a sugar solution and placed in water with a lower concentration of sugar, a series of events takes place that can lead to the sugar concentration inside and outside the vesicle becoming more equal. At first the vesicle expands as water enters. However, as the membrane stretches, a temporary hole opens up, which allows some of the excess solute molecules and water to escape, shrinking the vesicle. This sets up cycles of vesicle expansion and contraction that gradually lead to the solute concentrations on both sides of the membrane becoming more equal. This cyclical expansion and contraction of the vesicle also changes the membrane, decorating it with “domains” of specialized molecules, when expanded and uniform, when shrunk. It is possible that this process may have helped the first primitive cells to survive and, maybe, even benefit from changes in solute concentration in their environment.

Ceratitis capitata, is one of the most considerable invasive pests affecting fruit production worldwide. Conventional pesticides are generally formulated using organic solvents and emulsifiers that, in turn, are flammable and toxic. Thanks to their small size and biocompatibility, liposome-like formulations may significantly improve the efficacy and safety of conventional pesticides. This study aims to develop an alternative and innovative etofenprox formulation based on phospholipid vesicles (ethosomes) and evaluate its possible application for agricultural pest control. Ethosomes and geraniol-ethosomes were prepared by the one-step sonication method, achieving vesicles with small sizes (around 267 nm) and low polydispersity index (around 0.04). These vesicles were stable over 90 days of storage at room temperature and could slow the release of etofenprox (57 ± 4% released), in comparison with a commercial formulation (85 ± 5% released) after 24 h. Ethosomes and geraniol-ethosomes showed similar retention properties on lemon leaves (13.3 ± 1.0 to 14.4 ± 1.2 mg/cm 2 ) under laboratory condition. After open-field application, geraniol-ethosomes left the highest etofenprox residues on lemon leaves (14.3 ± 1.0 mg/kg), whereas the commercial formulation on the flavedo (4.1 ± 0.5 mg/kg). This result highlighted the possibility of reducing the application dose of etofenprox loaded in geraniol-ethosomes especially during the BBCH stage before fruiting. Both formulations displayed good biocompatibility with no significant cytotoxic effects on human keratinocytes (HaCat cells) across different etofenprox concentrations. Furthermore, laboratory bioassays revealed that geraniol-ethosomes exhibited a prolonged toxicity when sprayed against Ceratitis capitata adults, attributed to sustained release kinetics, underscoring their potential in environmentally sustainable agricultural pest management.

The purpose of this report is to summarize and critically analyze emerging trends in phospholipid vesicles for the oral delivery of natural compounds. Liposomes have long been used as delivery systems, thanks to their ability to incorporate diverse bioactives, their biocompatibility and safety. However, the efficacy of oral liposomes is hampered by their low stability under the harsh conditions of the gastrointestinal tract. Different approaches have been utilized with the aim of improving the stability of liposomes and the payload after oral administration. This report provides an overview on the phospholipid vesicles used for oral delivery of natural compounds, exploring the current strategies to improve their performance by modifying the lipid bilayer composition and assembly or the physical state.

The aim of the present study was to evaluate the effectiveness of a Cannonau pomace extract loaded in nutriosomes in intestinal oxidative stress and a subacute model of Parkinson disease and compare the results with those previously obtained with a Nasco pomace extract loaded in the same nutriosomes. In this study, Cannonau pomace was extracted using ultrasound-assisted maceration to obtain a polyphenol-rich extract. The extract at two different concentrations (5 and 10 mg/mL) was loaded in the same nutriosomes previously used to deliver Nasco pomace extract were loaded in nutriosomes. The main physico-chemical and technological characteristics of the obtained vesicles, along with their stability over time were measured. The in vitro biocompatibility and ability of nutriosomes to protect intestinal epithelial cells (Caco-2) from oxidative damages, were evaluated. Finally, the effectiveness of repeated administration of Cannonau extract in dispersion or loaded in nutriosomes against the neurotoxic effects in mice was evaluated. The resulting vesicles had uniform distribution, controlled the release of payloads, were biocompatible, like nutriosomes loading Nasco pomace extract, protected the intestinal cells against damages induced by hydrogen peroxide, in a better extent than the Nasco nutriosomes. However, no significant neuroprotective effects were observed in in vivo experiments performed using a subacute model of Parkinson disease, unlike previous results obtained with Nasco pomace extract loaded nutriosomes. This discrepancy is possibly due to the absence of key polyphenols like procyanidin B2 in the Cannonau extract, which are instead present in the Nasco extract. The findings suggest that while nutriosomes enhance the bioavailability and efficacy of grape pomace extracts in vitro, their therapeutic potential in vivo may depend on the specific phenolic profile of the extract used. Further research is needed to optimize formulations and explore synergistic combinations for improved neuroprotective outcomes.

The Brazilian berry scientifically known as jabuticaba is a fruit covered by a dark purple peel that is still rich in bioactives, especially polyphenols. Considering that, this work was aimed at obtaining an extract from the peel of jabuticaba fruits, identifying its main components, loading it in phospholipid vesicles specifically tailored for skin delivery and evaluating their biological efficacy. The extract was obtained by pressurized hot water extraction (PHWE), which is considered an easy and low dissipative method, and it was rich in polyphenolic compounds, especially flavonoids (ortho-diphenols and condensed tannins), anthocyanins (cyanidin 3-O-glucoside and delphinidin 3-O-glucoside) and gallic acid, which were responsible for the high antioxidant activity detected using different colorimetric methods (DPPH, FRAP, CUPRAC and metal chelation). To improve the stability and extract effectiveness, it was incorporated into ultradeformable phospholipid vesicles (transfersomes) that were modified by adding two different polymers (hydroxyethyl cellulose and sodium hyaluronate), thus obtaining HEcellulose-transfersomes and hyaluronan-transfersomes. Transfersomes without polymers were the smallest, as the addition of the polymer led to the formation of larger vesicles that were more stable in storage. The incorporation of the extract in the vesicles promoted their beneficial activities as they were capable, to a greater extent than the solution used as reference, of counteracting the toxic effect of hydrogen peroxide and even of speeding up the healing of a wound performed in a cell monolayer, especially when vesicles were enriched with polymers. Given that, polymer enriched vesicles may represent a good strategy to produce cosmetical and cosmeceutical products with beneficial properties for skin.

Liposomes have been used for several decades for the encapsulation of drugs and bioactives in cosmetics and cosmeceuticals. On the other hand, the use of these phospholipid vesicles in food applications is more recent and is increasing significantly in the last ten years. Although in different stages of technological maturity—in the case of cosmetics, many products are on the market—processes to obtain liposomes suitable for the encapsulation and delivery of bioactives are highly expensive, especially those aiming at scaling up. Among the bioactives proposed for cosmetics and food applications, vitamins are the most frequently used. Despite the differences between the administration routes (oral for food and mainly dermal for cosmetics), some challenges are very similar (e.g., stability, bioactive load, average size, increase in drug bioaccessibility and bioavailability). In the present work, a systematic review of the technological advancements in the nanoencapsulation of vitamins using liposomes and related processes was performed; challenges and future perspectives were also discussed in order to underline the advantages of these drug-loaded biocompatible nanocarriers for cosmetics and food applications.

Essential oils are well known for their biological properties, making them useful for the treatment of various diseases. However, because of their poor stability and high volatility, their potential cannot be fully exploited. The use of nanoformulations to deliver essential oils can solve these critical issues and amplify their biological activities. We characterized an essential oil from Satureja thymbra via GC–MS and HPLC–DAD to provide qualitative and quantitative data. The essential oil was formulated in phospholipid vesicles which were characterized for size, surface charge, and storage stability. The entrapment efficiency was evaluated as the quantification of the major monoterpenoid phenols via HPLC–DAD. The morphological characterization of the vesicles was carried out via cryo-TEM and SAXS analyses. The essential oil’s antioxidant potential was assayed via two colorimetric tests (DPPH• and FRAP) and its cytocompatibility was evaluated in HaCaT skin cell cultures. The results showed that the nanoformulations developed for the loading of S. thymbra essential oil were below 100 nm in size, predominantly unilamellar, stable in storage, and had high entrapment efficiencies. The vesicles also displayed antioxidant properties and high cytocompatibility. These promising findings pave the way for further investigation of the therapeutic potential of S. thymbra nanoformulations upon skin application.

The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines.

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71–100 is shown as a promising broad-spectrum antiviral candidate.

Due to their high biocompatibility, biodegradability, and facile surface functionalization, phospholipid vesicles as carriers have garnered significant attention in the realm of disease diagnosis and treatment. On the one hand, phospholipid vesicles can function as probes for the detection of various diseases by encapsulating nanoparticles, thereby enabling the precise localization of pathological changes and the monitoring of disease progression. On the other hand, phospholipid vesicles possess the capability to selectively target and deliver therapeutic agents, including drug molecules, genes and immune modulators, to affected sites, thereby enhancing the sustained release of these agents and improving therapeutic efficacy. Recent advancements in nanotechnology have led to an increased focus on the application of phospholipid vesicles in drug delivery, biological detection, gene therapy, and cell mimics. This review aims to provide a concise overview of the structure, characteristics, and preparation techniques of phospholipid vesicles of varying sizes. Furthermore, we will summarize the latest research developments regarding their use as nanomedicines and gene carriers in disease treatment. Additionally, we will elucidate the potential of phospholipid vesicles in facilitating the internalization, controlled release, and targeted delivery of therapeutic substrates. Through this review, we aspire to enhance the understanding of the evolution of phospholipid vesicles within the biological field, outline prospective research, and address the forthcoming challenges associated with phospholipid vesicles in disease diagnosis and treatment.