Search Results (116)

This study developed phospholipid-based liposomes loaded with extract from wild thyme (Thymus serpyllum L.) tea processing residues to enhance polyphenol stability and delivery. Liposomes were prepared with phospholipids alone or combined with 10–30 mol% cholesterol or β-sitosterol. The effect of different lipid compositions on encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential, stability, thermal properties, diffusion coefficient, and diffusion resistance of the liposomes was investigated. Liposomes with 10 mol% sterols (either cholesterol or β-sitosterol) exhibited the highest EE of polyphenols, while increasing sterol content to 30 mol% resulted in decreased EE. Particle size and PDI increased with sterol content, while liposomes prepared without sterols showed the smallest vesicle size. Encapsulation of the extract led to smaller liposomal diameters and slight increases in PDI values. Zeta potential measurements revealed that sterol incorporation enhanced the surface charge and stability of liposomes, with β-sitosterol showing the most pronounced effect. Stability testing demonstrated minimal changes in size, PDI, and zeta potential during storage. UV irradiation and lyophilization processes did not cause significant polyphenol leakage, although lyophilization slightly increased particle size and PDI. Differential scanning calorimetry revealed that polyphenols and sterols modified the lipid membrane transitions, indicating interactions between extract components and the liposomal bilayer. FT-IR spectra confirmed successful integration of the extract into the liposomes, while UV exposure did not significantly alter the spectral features. Thiobarbituric acid reactive substances (TBARS) assay demonstrated the extract’s efficacy in mitigating lipid peroxidation under UV-induced oxidative stress. In contrast, liposomes enriched with sterols showed enhanced peroxidation. Polyphenol diffusion studies showed that encapsulation significantly delayed release, particularly in sterol-containing liposomes. Release assays in simulated gastric and intestinal fluids confirmed controlled, pH-dependent polyphenol delivery, with slightly better retention in β-sitosterol-enriched systems. These findings support the use of β-sitosterol- and cholesterol-enriched liposomes as stable carriers for polyphenolic compounds from wild thyme extract, as bioactive antioxidants, for food and nutraceutical applications. Full article

Aggregation of tau protein is a hallmark feature of tauopathies such as Alzheimer’s disease. The microtubule-binding domain of tau plays a crucial role in the tau aggregation process. In this study, we investigated the dual effects of membrane interactions of tau_298–317, a fragment peptide from the microtubule-binding domain, on peptide-induced membrane disruption and membrane-mediated peptide self-assembly. Our results show that neither wild-type tau_298–317 nor its P301L or Ser305-phosphorylated mutants aggregate in the presence of zwitterionic POPC vesicles or cause lipid vesicle leakage, indicating weak peptide–membrane interactions. In contrast, tau_298–317 strongly interacts with negatively charged POPG liposomes, leading to a rapid transition of the peptide conformation from random coils to α-helical intermediate conformation upon membrane adsorption, which may further promote peptide self-association to form oligomers and β-sheet-rich fibrillar structures. Tau_298–317-induced rapid POPG membrane leakage indicates a synergistic process of the peptide self-assembly at the membrane interface and the aggregation-induced membrane disruption. Notably, phosphorylation at Ser305 disrupts favorable electrostatic interactions between the peptide and POPG membrane surface, thus preventing peptide aggregation and membrane leakage. In contrast, the P301L mutation significantly enhances membrane-mediated peptide aggregation and peptide-induced membrane disruption, likely due to alleviation of local conformational constraints and enhancement of local hydrophobicity, which facilitates fast conformational conversion to β-sheet structures. These findings provide mechanistic insights into the molecular mechanisms underlying membrane-mediated aggregation of crucial regions of tau and peptide-induced membrane damage, indicating potential strategies to prevent tau aggregation and membrane rupture by targeting critical electrostatic interactions between membranes and key local regions of tau. Full article

Herpes simplex virus type 1 (HSV-1) is a widespread pathogen responsible for recurrent infections, primarily affecting the skin and mucous membranes. With the aim of targeting both the viral infection and the associated inflammatory response, biotechnologically produced Lavandula angustifolia Miller (L. angustifolia) extract, rich in rosmarinic acid, was incorporated into liposomal formulations intended for topical application. Lavender is known for its strong anti-inflammatory, antioxidant, wound-healing, and antiviral properties. However, its low stability under certain conditions limits its therapeutic potential. Four different formulations were developed: conventional liposomes, glycerosomes, hyalurosomes, and glycerohyalurosomes. The vesicles were characterized for size, stability, and entrapment efficiency. Glycerosomes were the smallest (~58 nm), while the other formulations ranged around 77 nm, all maintaining a highly negative surface charge, ensuring stability and reduced aggregation. Glycerol-containing formulations demonstrated superior stability over 12 months, while liposomes and hyalurosomes increased their size after only two months. Entrapment efficiency reached up to 100% for most vesicles, except for glycerohyalurosomes (~54%). In vitro studies on Normal Human Dermal Fibroblasts (NHDFs) demonstrated that all formulations were biocompatible and enhanced cell viability under oxidative stress. Glycerosomes, hyalurosomes, and glycerohyalurosomes exhibited significant anti-inflammatory activity by reducing MMP-1 and IL-6 levels in LPS-stimulated fibroblasts. Furthermore, these preliminary results highlighted promising antiviral activity against HSV-1 of the obtained formulations, particularly when applied during or post-infection. Overall, these phospholipid vesicles offer a dual therapeutic approach, combining antioxidant, anti-inflammatory, and antiviral effects, positioning them as promising candidates for the treatment of HSV-induced skin lesions and related inflammatory conditions. Full article

Background/Objectives: Thymol, one of the main compounds of thyme essential oil, has shown promising effects in treating various skin disorders owing to its anti-inflammatory, antimicrobial and antioxidative activities. Due to its limited solubility in water, thymol is commonly used in higher concentrations to achieve a suitable therapeutic effect, which can consequently lead to skin irritation. To overcome these limitations, we incorporated thymol into a vesicular phospholipid gel (VPG), a novel semisolid dermal vehicle consisting of highly concentrated dispersion of phospholipid vesicles (liposomes). Methods: Thymol was successfully loaded into two VPGs differing in bilayer fluidity, which were characterized for the physicochemical and rheological properties, storage stability, in vitro release, ex vivo skin permeability, in vitro compatibility with epidermal cells, wound healing potential, and antibacterial activity against skin-relevant bacterial strains. Results: High pressure homogenization method enabled preparation of VPG-liposomes of neutral surface charge in the size range 140–150 nm with polydispersity indexes below 0.5. Both types of VPGs exhibited viscoelastic solid-like structures appropriate for skin administration and ensured skin localization of thymol. Although both types of VPGs enabled prolonged release of thymol, the presence of cholesterol in the VPG increased the rigidity of the corresponding liposomes and further slowed down thymol release. Conclusions: Loading of thymol into VPGs significantly reduced its cytotoxicity toward human keratinocytes in vitro even at very high concentrations, compared to free thymol. Moreover, it facilitated in vitro wound healing activity, proving its potential as a vehicle for herbal-based medicines. However, the antibacterial activity of thymol against Staphylococcus aureus and methicillin-resistant S. aureus was hindered by VPGs, which represents a challenge in their development. Full article

Diffusiophoresis of a weakly charged dielectric droplet in a cylindrical pore is investigated theoretically in this study. The governing fundamental electrokinetic equations are solved with a patched pseudo-spectral method based on Chebyshev polynomials, coupled with a geometric mapping scheme to take care of the irregular solution domain. The impact of the boundary confinement effect upon the droplet motion is explored in detail, which is most profound in narrow channels. We found, among other things, that the droplet moving direction may reverse with varying channel widths. Enhanced motion-inducing double-layer polarization due to the presence of a nearby channel wall is found to be responsible for it. In particular, an interesting and seemingly peculiar phenomenon referred to as the “solidification phenomenon” is observed here at some specific critical droplet sizes or electrolyte strengths in narrow channels, under which all the droplets move at identical speeds regardless of their viscosities. They move like a rigid particle without the surface spinning motions and the induced interior recirculating vortex flows. As the corresponding shear rate is zero at this point, the droplet is resilient to undesirable exterior shear stresses tending to damage the droplet in motion. This provides a helpful guideline in the fabrication of liposomes in drug delivery in terms of the optimal liposome size, as well as in the microfluidic and nanofluidic manipulations of cells, among other potential practical applications. The effects of other parameters of electrokinetic interest are also examined. Full article

Spirulina (Arthrospira platensis) is a microalga widely used as a dietary supplement in sports nutrition and in treating metabolic diseases such as diabetes, obesity and metabolic syndrome. Spirulina’s cell structure limits digestibility and reduces the availability of bioactive compounds. The extraction processes, coupled with encapsulation, can enhance the bioavailability of nutritional and antioxidant compounds, protecting them from degradation, preserving their functional activity, and supporting controlled release. The physicochemical properties of liposomes (Lps), bilosomes (Bls), and gelatin-enriched bilosomes (G-Bls) with incorporated Spirulina extracts were investigated. The delivery systems exhibited small particle size (101.8 ± 0.5 to 129.7 ± 1.2 nm), homogeneous distribution (polydispersity index (PDI) 0.17 ± 6.67 to 0.33 ± 9.06), negative surface charges (−31.9 ± 5.2 to 31.1 ± 6.4 mV), and high entrapment efficiency (>80%). G-Bls demonstrated effective retention of the extract, with a low release rate at pH 1.2 (41.8% ± 6.1) and controlled release at pH 7.0 (52.5% ± 3.0). Biocompatibility studies on Caco-2 cells showed that G-Bls maintained high cell viability at 200 μg·mL⁻¹ (87.89% ± 10.35) and significantly mitigated H₂O₂-induced oxidative stress at 20 and 200 μg·mL⁻¹, increasing cell viability by 23.47% and 19.28%. G-Bls are a promising delivery system for enhancing the stability, bioavailability, and protective effects of Spirulina extracts, supporting their potential application in dietary supplements aimed at promoting sports performance and recovery, mitigating exercise-induced oxidative stress, and managing metabolic disorders. Full article

The complexes of negatively charged polysaccharides with lipid vesicles have been shown to have applications in medicine, bioremediation, water purification, and construction of nano-biosensors. This article presents research on the formation of these complexes based on the interactions between three types of liposomes, DOPC liposomes (which contain a lipid bilayer in the liquid-disordered (Ld) state), RAFT liposomes (which contain liquid-ordered (Lo) lipid raft domains surrounded by lipids in the Ld state) and SPH–CHL liposomes (which contain a lipid bilayer in the Lo state), and two selected anionic polysaccharides, polysialic acid (PSA) and polygalacturonic acid (PGA). The analysis was conducted using a toluidine blue (TB) probe and the absorption spectroscopy technique. In contrast to DOPC and SPH–CHL liposomes, binding of negatively charged PSA or PGA chains to RAFT liposomes induced a TB absorption maximum shift from 630 nm to 560 nm. The obtained results indicate that toluidine blue can be applied for monitoring the formation of these nano-complexes, and that the boundaries between Ld/Lo domains within membranes in RAFT liposomes can significantly enhance the binding affinity of negatively charged polysaccharides to the lipid bilayer surface. The observed metachromatic shift in TB absorption suggests that negatively charged PSA and PGA chains interact with the Ld/Lo boundaries within RAFT liposome membranes. Full article

Background/Objectives: This study aimed to develop liposomes derived from lipids obtained from red blood cell membranes for potential use in antitumor applications. Hemoglobin hydrolysates exhibiting peptides with known antitumor activities were encapsulated within these liposomes. Methods: The developed liposomal systems were characterized by their physicochemical properties, including size, surface charge, and encapsulation efficiency, and tested in vitro against 4T1 breast cancer cells and NIH3T3 fibroblasts. Results: Results indicated that the liposomes achieved effective encapsulation (88.9%), with nanometer-scale sizes (ranging from 140.7 nm for Blank-Liposomes to 658.3 nm for Pep-Liposomes) and stable colloidal properties. Conclusions: Although cytotoxicity was limited, the use of liposomes from endogenous components, such as red blood cells, demonstrates promise as a complementary approach in anticancer therapy. Full article

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disorder with limited therapeutic options, particularly for refractory discoid lupus (DLE), which often results in scarring and atrophy. Recent studies have identified miR-31, miR-485-3p, and miR-885-5p as key regulators of inflammation, apoptosis, and fibrosis in CLE skin lesions. This research investigates a novel topical miRNA therapy using DDC642 elastic liposomes to target these pathways in CLE. DDC642 liposomes were complexed with miRNAs (anti-miR-31, anti-miR-485-3p, pre-miR-885-5p) and characterized through dynamic light scattering and Cryo-TEM. Cytotoxicity, cellular penetration, and therapeutic efficacy were evaluated in primary keratinocytes, PBMCs, and immune 3D-skin organoids. miRNA lipoplexes were successfully synthesized with optimized particle size, surface charge, and encapsulation efficiency. These lipoplexes exhibited effective cellular penetration and low cytotoxicity. Anti-miR-31 lipoplexes reduced miR-31 and NF-κB levels while increasing STK40 and PPP6C expression. Pre-miR-885-5p lipoplexes elevated miR-885-5p levels and downregulated PSMB5 and NF-κB in keratinocytes. While anti-miR-485-3p lipoplexes reduced T-cell activation markers. Anti-miR-31 and pre-miR-885-5p lipoplexes successfully modulated inflammatory pathways in 3D-skin CLE models. miRNA lipoplexes represent promising candidates for pioneering topical genetic therapies for CLE. Further studies, including animal models, are necessary to validate and optimize these findings. Full article

Background/Objectives: Sodium acetate (NaA) has demonstrated potential in improving non-alcoholic fatty liver disease (NAFLD) by targeting hepatocytes and Kupffer cells. However, its clinical application is hindered by low oral bioavailability and insufficient liver concentrations. Liposomes, with their capacity to encapsulate water-soluble drugs and be surface-modified, offer a promising solution for targeted oral drug delivery. Methods: We designed NaA-loaded liposomes modified with sodium cholate (SC) and mannose (MAN) (NaA@SC/MAN-LPs) to target hepatocytes and Kupffer cells. Results: The NaA@SC/MAN-LPs had a mean diameter of approximately 100 nm with a positive surface charge. Compared to free NaA, NaA@SC/MAN-LPs significantly extended the serum half-life from 2.85 h to 15.58 h, substantially improving in vivo bioavailability. In vivo distribution studies revealed that NaA@SC/MAN-LPs extended the acetate peak time in the liver from 15 min to 60 min and increased hepatic acetate accumulation to 3.75 times that of free NaA. In in vitro cell experiments, NaA@SC/MAN-LPs significantly reduced the lipid droplet, triglycerides (TG), and total cholesterol (TC) in a fatty acid-induced hepatocyte steatosis model and suppressed proinflammation in a lipopolysaccharide (LPS)-activated Kupffer cell inflammation model. Free NaA effectively improved hepatic lipid deposition in NAFLD mice. Furthermore, NaA@SC/MAN-LPs decreased hepatic TG, TC, and the relative area of lipid droplets by 30.44%, 15.26%, and 55.83%, compared to free NaA. Furthermore, the liposomes reduced macrophage infiltration and pro-inflammatory response. Conclusions: The NaA@SC/MAN-LPs demonstrated effective dual targeting effects on hepatocytes and Kupffer cells, significantly improving the pathogenesis of NAFLD, compared to free NaA. This study provides a new strategy for developing effective and safe oral drugs for NAFLD. Full article

Objectives: Liposomes are a promising drug carrier for inhaled delivery systems and their physical parameters could influence therapeutic efficacy significantly. This study was designed to answer the specific question of the proper surface charge of liposomes in pulmonary inhalation, as well as to study the synergistic anti-inflammation efficacy between drugs. Methods: In this work, a series of drug-loaded liposomes with different surface charges (from negative to positive) were prepared, and several in vitro and in vivo assays, including cytotoxicity, hemolysis assay, mucus penetration and lipopolysaccharide (LPS)-induced pneumonia model test, were adopted to evaluate the anti-inflammation efficacy and biocompatibility of the above liposomes. Results: Compared with cationic liposomes, anionic liposomes are capable of better mucus penetration and good biocompatibility (low cytotoxicity, better blood compatibility and mild tissue inflammation), but with poor cellular uptake by immune cells. In specific, even when the liposome surface charge was only +2.6 mV, its cytotoxicity and blood hemolysis reached around 20% and 15%, respectively. Furthermore, there was no significant difference in biocompatibility between anionic liposomes (−25.9 vs. −2.5 mV), but a slightly negative-charged liposome exhibited better cellular uptake. Conclusions: Thus, slightly negative-charged liposomes (−1~−3 mV) could be a well inhaled drug carrier considering both efficacy and biocompatibility. In an LPS-induced pneumonia mouse model, the drug-loaded liposomes achieved better anti-inflammatory efficacy compared with free drugs. Full article

Background/Objectives: The purpose of this study was to create bile acid-containing liposomes to improve methotrexate blood-brain barrier penetration and to assess the liposome transportation mechanism across the blood–brain barrier. Methods: The improvement of liposome penetration was investigated utilizing human brain microvascular endothelial cells in an in vitro blood-brain barrier model. Using confocal laser scanning microscopy (CLSM) and flow cytometry, liposomes were labeled with fluorescent phospholipids to facilitate their passage across the blood–brain barrier. Results: The produced liposomes with bile acid exhibited a negative surface charge and an average particle size of between 30 and 148 nm. According to an in vitro blood-brain barrier penetration study, the methotrexate penetration was increased by liposomes containing 1% glycocholic acid but not by liposomes containing taurocholic acid. For transport pathway evaluation across the blood-brain barrier of these liposomes, CLSM revealed that fluorescent liposomes were present inside cells treated with specific endocytosis inhibitors, indicating that the cellular internalization of the particles was not involved in endocytosis. Conclusions: Liposomes supplemented with 1% glycocholic acid could enhance the penetration of methotrexate across the blood-brain barrier, while taurocholic acid could not. The transport of liposomes with 1% glycocholic acid across the blood-brain barrier occurs via the transcellular pathway through which it penetrates cells. In contrast, the paracellular pathway was a minor pathway. Full article

This study aims to contribute to the physical understanding of the behavior of nanoparticles in lipid–nanoparticle composite systems. Therefore, composite films were formed on hydrophilic or hydrophobic surfaces through the sequential adsorption of liposomes and silica nanoparticles. The process was performed using dispersions with different pHs by using optical fixed-angle reflectometry. In the first step, liposomes were deposited on the surface, resulting in a lipid monolayer or bilayer depending on the surface’s properties. The kinetic experiments indicated that the adsorption of liposomes is a diffusion-limited process that depends on the pH and the properties of the substrate. In the second step, negatively charged nanoparticles were adsorbed on the membrane as a result of the electrostatic interactions with the positively charged domains on the membrane. The amounts of liposomes and particles adsorbed depend on the charge density of the particles and net charge density of the membrane: an increase in the pH and hydrophobicity of the surface leads to a decrease in the amounts adsorbed because of the increase in the electrostatic repulsion between particles and lipids. The procedure was supplemented with the formation of two liposomes/nanoparticles bilayers. Full article

Liposome-based drug delivery technologies have showed potential in enhancing medication safety and efficacy. Innovative drug loading and release mechanisms highlighted in this review of next-generation liposomal formulations. Due to poor drug release kinetics and loading capacity, conventional liposomes have limited clinical use. Scientists have developed new liposomal carrier medication release control and encapsulation methods to address these limits. Drug encapsulation can be optimized by creating lipid compositions that match a drug’s charge and hydrophobicity. By selecting lipids and adding co-solvents or surfactants, scientists have increased drug loading in liposomal formulations while maintaining stability. Nanotechnology has also created multifunctional liposomes with triggered release and personalized drug delivery. Surface modification methods like PEGylation and ligand conjugation can direct liposomes to disease regions, improving therapeutic efficacy and reducing off-target effects. In addition to drug loading, researchers have focused on spatiotemporal modulation of liposomal carrier medication release. Stimuli-responsive liposomes release drugs in response to bodily signals. Liposomes can be pH- or temperature-sensitive. To improve therapeutic efficacy and reduce systemic toxicity, researchers added stimuli-responsive components to liposomal membranes to precisely control drug release kinetics. Advanced drug delivery technologies like magnetic targeting and ultrasound. Pro Drug, RNA Liposomes approach may improve liposomal medication administration. Magnetic targeting helps liposomes aggregate at illness sites and improves drug delivery, whereas ultrasound-mediated drug release facilitates on-demand release of encapsulated medicines. This review also covers recent preclinical and clinical research showing the therapeutic promise of next-generation liposomal formulations for cancer, infectious diseases, neurological disorders and inflammatory disorders. The transfer of these innovative liposomal formulations from lab to clinical practice involves key difficulties such scalability, manufacturing difficulty, and regulatory limits. Full article

The National Cancer Institute (NCI) recognizes the potential of technologies based on the use of nanoparticles (NPs) in revolutionizing clinical approaches to the diagnosis and prognosis of cancer. Recent research suggests that once NPs come into contact with the biological fluid of cancer patients, they are covered by proteins, forming a “protein corona” composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between patients with and without cancer, has been introduced. We developed the design of an experimental prospective single-center study with patients allocated in a 1:1:1 ratio of one of three arms: untreated patients with benign prostatic hyperplasia (BPH), untreated patients with non-metastatic prostate cancer (PCa), and metastatic prostate cancer patients starting systemic therapies with new androgen-targeted agents or taxanes. The protocol aims to develop and implement sensitive nanotools with two distinct objectives: First, to design NPs capable of selectively binding and detecting biomarkers in order to build a predictive diagnostic model to effectively discriminate between patient sera affected by BPH and PCa. Secondly, within the population with PCa, in the case of initial advanced metastatic diagnosis, the objective is to find biomarkers capable of predicting the response to systemic treatments to improve the precision and efficiency of monitoring treatment outcomes. For protein and metabolite corona experiments, we developed a cross-reactive sensor array platform with cancer detection capacity made of three liposomal formulations with different surface charges. For proteomic-NP studies, proteins were identified and quantified using nano-high-performance LC (nanoHPLC) coupled with MS/MS (nanoHPLC−MS/MS). Metabolites were instead analyzed using an untargeted metabolomic approach. Compared with previous review articles, the novelty of this review is represented by the analysis of the possible clinical applications of protein corona NPs focused on PCa and the presentation of a new clinical protocol in the metastatic phase of PCa. Full article