Search Results (16)

The biological complexity of sarcopenia presents a major challenge for therapeutic intervention due to the wide range of degenerative changes it induces in skeletal muscle. This study demonstrates the potential of liposomal controlled release systems to address these challenges by combining two bioactive agents with complementary actions: caffeine (CAF), encapsulated in DMPC-based liposomes, and hyaluronic acid methacrylate (HAMA), encapsulated in DOPC-based liposomes. A hybrid system was also developed to deliver both substances simultaneously, aiming to restore tissue function through combined metabolic, anti-inflammatory, and regenerative effects. The liposomes exhibited nanoscale dimensions, spherical morphology, and intact membrane structure, as confirmed by electron microscopy. DLS analysis indicated good colloidal stability and monodisperse size distribution across all formulations, with improved stability observed in the hybrid system. Drug release studies showed a time-dependent profile, with HAMA releasing rapidly and CAF releasing gradually, supporting a dual-action therapeutic approach tailored to the multifactorial pathology of sarcopenia. The biological assays, performed in an established in vitro sarcopenia model, revealed the potential of liposomes co-delivering caffeine and HAMA to mitigate oxidative stress, preserve mitochondrial function, and reduce apoptosis in H₂O₂-damaged myotubes. Full article

Effective postoperative pain management remains a major clinical challenge in spinal surgery, with poorly controlled pain affecting up to 50% of patients and contributing to delayed mobilization, prolonged hospitalization, and risk of chronic postsurgical pain. This review synthesizes current and emerging strategies in postoperative spinal pain management, tracing the evolution from opioid-centric paradigms to individualized, multimodal approaches. Multimodal analgesia (MMA) has become the cornerstone of contemporary care, combining pharmacologic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and gabapentinoids, with regional anesthesia techniques, including erector spinae plane blocks and liposomal bupivacaine. Adjunctive nonpharmacologic modalities like early mobilization, cognitive behavioral therapy, and mindfulness-based interventions further optimize recovery and address the biopsychosocial dimensions of pain. For patients with refractory pain, neuromodulation techniques such as spinal cord and peripheral nerve stimulation offer promising results. Advances in artificial intelligence (AI), biomarker discovery, and nanotechnology are poised to enhance personalized pain protocols through predictive modeling and targeted drug delivery. Enhanced recovery after surgery protocols, which integrate many of these strategies, have been shown to reduce opioid use, hospital length of stay, and complication rates. Nevertheless, variability in implementation and the need for individualized protocols remain key challenges. Future directions include AI-guided analytics, regenerative therapies, and expanded research on long-term functional outcomes. This review provides an evidence-based framework for pain control following spinal surgery, emphasizing integration of multimodal and innovative approaches tailored to diverse patient populations. Full article

The concept and feasibility of producing liposomes by rehydrating engineered lipid nanoconstructs are demonstrated in this study. Nanoconstructs of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were produced using a microfluidic delivery probe integrated with an atomic force microscope. The subsequent rehydration of these POPC constructs led to the formation of liposomes, most of which remained adhered to the surface. The size (e.g., diameter) of the liposomes could be tuned by varying the lateral dimension of the lipid constructs. Hierarchical liposomal structures, such as pentagons containing five liposomes at the corners, could also be designed and produced by depositing lipid constructs to designated locations on the surfaces, followed by rehydration. This new means allows for regulating liposomal sizes, distributions, and compositions. The outcomes benefit applications of liposomes as delivery vehicles, sensors, and building blocks in biomaterials design. The ability to produce hierarchical liposomal structures benefits numerous applications such as proto-cell development, multiplexed bio-composite materials, and the engineering of local bio-environments. Full article

Cell mechanics are a biophysical indicator of cell state, such as cancer metastasis, leukocyte activation, and cell cycle progression. Atomic force microscopy (AFM) is a widely used technique to measure cell mechanics, where the Young modulus of a cell is usually derived from the Hertz contact model. However, the Hertz model assumes that the cell is an elastic, isotropic, and homogeneous material and that the indentation is small compared to the cell size. These assumptions neglect the effects of the cytoskeleton, cell size and shape, and cell environment on cell deformation. In this study, we investigated the influence of cell size on the estimated Young’s modulus using liposomes as cell models. Liposomes were prepared with different sizes and filled with phosphate buffered saline (PBS) or hyaluronic acid (HA) to mimic the cytoplasm. AFM was used to obtain the force indentation curves and fit them to the Hertz model. We found that the larger the liposome, the lower the estimated Young’s modulus for both PBS-filled and HA-filled liposomes. This suggests that the Young modulus obtained from the Hertz model is not only a property of the cell material but also depends on the cell dimensions. Therefore, when comparing or interpreting cell mechanics using the Hertz model, it is essential to account for cell size. Full article

The present study analyzes (theoretically and experimentally) a drug release process from nanoparticles (polymeric nanocapsules and liposomes). This process is functionalized on the surface with an aptamer. These types of drug release processes can also be included in cream-type formulations. The obtained cream ensures the active targeting of tumor epithelial cells, in the case of skin cancer, because it can be easily administered to the skin by spreading, thus avoiding side effects caused by the toxicity of the drug to healthy cells, increasing both patient compliance and the effectiveness of the treatment. The process of obtaining these formulations is a simple one, easy to use and highly reproductible. The theoretical model, based on the multifractal tunnel effect within the Scale Relativity Theory, considers the system as a complex one. In this model, complexity is replaced with system multifractality, quantified in physical quantities as multifractal dimensions and multifractal functions. The main advantage of this approach consists in the fact that it allows us to obtain information on system behavior at a microscopic level and to evaluate microscopic characteristics of the system, such as intrinsic transparences of the drug molecules, multifractal constants as indicators of the system’s complexity, the frequency of interactions within the system and the energy ratio between potential barrier energy and the energy of drug molecules. Full article

Chronic wounds are a growing problem for both society and patients. They generate huge costs for treatment and reduce the quality of life of patients. The greatest challenge when treating a chronic wound is prolonged infection, which is commonly caused by biofilm. Biofilm makes bacteria resistant to individuals’ immune systems and conventional treatment. As a result, new treatment options, including nanomaterials, are being tested and implemented. Nanomaterials are particles with at least one dimension between 1 and 100 nM. Lipids, liposomes, cellulose, silica and metal can be carriers of nanomaterials. This review’s aim is to describe in detail the mode of action of those molecules that have been proven to have antimicrobial effects on biofilm and therefore help to eradicate bacteria from chronic wounds. Nanoparticles seem to be a promising treatment option for infection management, which is essential for the final stage of wound healing, which is complete wound closure. Full article

In this work, a lipophilic ophthalmic drug, lutein, has been entrapped in liposomes, using a supercritical assisted process. Effects of pressure, temperature, and drug to lipid ratio variation were studied on mean diameters and lutein encapsulation efficiency. Liposomes with diameters between 153 ± 38 and 267 ± 56 nm were produced, and lutein encapsulation efficiencies between 86.5 ± 0.4% and 97.8 ± 1.2% were obtained. A Scanning Electron Microscope confirmed spherical shape and mean dimensions of vesicles. The variation of temperature for the production of liposomes showed a significant impact on lutein retention time in the double lipidic layer. Lutein drug release from liposomes produced at 35 °C ended in almost 4.5 days; whereas, liposomes produced at 40 °C showed a faster lutein release in 3 days; then, vesicles obtained at 45 °C released their lutein content in only 2 days. Drug release raw data were well-fitted using Weibull model (R² up to 99%). Full article

Chemotherapy drugs (CDs) disrupt the lipid membrane’s insulation properties by inducing stable ion pores across bilayer membranes. The underlying molecular mechanisms behind pore formation have been revealed in this study using several methods that confirm molecular interactions and detect associated energetics of drugs on the cell surface in general and in lipid bilayers in particular. Liposome adsorption and cell surface binding of CD colchicine has been demonstrated experimentally. Buffer dissolved CDs were considerably adsorbed in the incubated phospholipid liposomes, measured using the patented ‘direct detection method’. The drug adsorption process is regulated by the membrane environment, demonstrated in cholesterol-containing liposomes. We then detailed the phenomenology and energetics of the low nanoscale dimension cell surface (membrane) drug distribution, using atomic force microscopy (AFM) imaging what addresses the surface morphology and measures adhesion force (reducible to adhesive energy). Liposome adsorption and cell surface binding data helped model the cell surface drug distribution. The underlying molecular interactions behind surface binding energetics of drugs have been addressed in silico numerical computations (NCs) utilizing the screened Coulomb interactions among charges in a drug–drug/lipid cluster. Molecular dynamics (MD) simulations of the CD-lipid complexes detected primarily important CD-lipid electrostatic and van der Waals (vdW) interaction energies. From the energetics point of view, both liposome and cell surface membrane adsorption of drugs are therefore obvious findings. Colchicine treated cell surface AFM images provide a few important phenomenological conclusions, such as drugs bind generally with the cell surface, bind independently as well as in clusters of various sizes in random cell surface locations. The related adhesion energy decreases with increasing drug cluster size before saturating for larger clusters. MD simulation detected electrostatic and vdW and NC-derived charge-based interactions explain molecularly of the cause of cell surface binding of drugs. The membrane binding/association of drugs may help create drug–lipid complexes with specific energetics and statistically lead to the creation of ion channels. We reveal here crucial molecular understanding and features of the pore formation inside lipid membranes that may be applied universally for most of the pore-forming existing agents and novel candidate drugs. Full article

This work was aimed at enhancing butamben (BTB) anesthetic efficacy by the “drug-in cyclodextrin (CD)-in deformable liposomes” strategy. In the study, phase-solubility studies with natural (α-, β-, γ-) and derivative (hydroxypropyl-α-and β-, sulfobutylether-β, methyl-β) CDs evidenced the highest BTB affinity for βCD and its derivatives and indicated methyl-βCD (RAMEB) as the best carrier. Drug-RAMEB complexes were prepared by different techniques and were characterized for solid-state and dissolution properties. The best BTB–RAMEB product was chosen for entrapment in the aqueous core of deformable liposomes containing stearylamine, either alone or with sodium cholate, as edge activators. Double-loaded (DL) liposomes, bearing the lipophilic drug (0.5% w/v) in the bilayer and its hydrophilic RAMEB complex (0.5% w/v) in the aqueous core, were compared to single-loaded (SL) liposomes bearing 1% w/v plain drug in the bilayer. All vesicles showed homogeneous dimensions (i.e., below 300 nm), high deformability, and excellent entrapment efficiency. DL-liposomes were more effective than SL ones in limiting drug leakage (<5% vs. >10% after a 3 months storage at 4 °C). In vivo experiments in rabbits proved that all liposomal formulations significantly (p < 0.05) increased the intensity and duration of drug anesthetic action compared to its hydroalcoholic solution; however, DL liposomes were significantly (p < 0.05) more effective than SL ones in prolonging BTB anesthetic effect, owing to the presence of the drug-RAMEB complex in the vesicle core, acting as a reservoir. DL liposomes containing both edge activators were found to have the best performance. Full article

Medical and pharmaceutical research has shown that liposomes are very efficient in transporting drugs to targets. In this study, we prepared six liposome formulas, three in which we entrapped caffeic acid (CA), and three with only phospholipids and without CA. Determination of entrapment efficiency (EE) showed that regardless of the phospholipids used, the percentage of CA entrapment was up to 76%. The characterization of the liposomes was performed using Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), zeta potential and polydispersity and showed that about 75–99% of the liposomes had dimensions between 40 ± 0.55–500 ± 1.45 nm. The size and zeta potential of liposomes were influenced by the type of phospholipid used to obtain them. CA release from liposomes was performed using a six-cell Franz diffusion system, and it was observed that the release of entrapped CA occurs gradually, the highest amount occurring in the first eight hours (over 80%), after which the release is much reduced. Additionally, the time stability of the obtained liposomes was analysed using univariate and multivariate statistical analysis. Therefore, liposomes offer great potential in CA entrapment. Full article

Liposomes are spherical vesicles made up of an aqueous core surrounded by phospholipids. These delivery systems (DS) are largely employed as drug carriers in several industrial fields, such as pharmaceutical and nutraceutical fields. The aim of this short review is to provide a fast overview on the main fundamentals of liposomes, thought as a compact guide for researchers and students that want to approach this topic for the first time. The mini-review will focus on the definitions, production methods and characterization protocols of the liposomes produced, making a critical comparison of the main conventional and supercritical based manufacturing methods available. The literature was analyzed deeply from the first works by Dr. Bangham in 1965 to the most recent supercritical fluid applications. The advantages and disadvantages of conventional and high-pressure processes will be described in terms of solvent elimination, production at the nanometric (50–300 nm) and micrometric level (1–100 μm) and encapsulation efficiency (20–90%). The first proposed methods were characterized by a low encapsulation efficiency (20–40%), resulting in drug loss, a high solvent residue and high operating cost. The repeatability of conventional processes was also low, due to the prevalent batch mode. Supercritical-assisted methods were developed in semi-continuous layouts, resulting in an easy process scale-up, better control of liposome dimensions (polydispersity index, PDI) and also higher encapsulation efficiencies (up to 90%). Full article

Free-radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions, have a trans-disciplinary relevance. Cardiolipins (CL, (1,3-diphosphatidyl-sn-glycerol)) and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipids, where they maintain membrane integrity and regulate enzyme functionalities. Peroxidation pathways and fatty acid remodeling are known causes of mitochondrial disfunctions and pathologies, including cancer. Free-radical-mediated isomerization with the change of the cis CL into geometrical trans isomers is an unknown process with possible consequences on the supramolecular membrane lipid organization. Here, the formation of mono-trans CL (MT-CL) and other trans CL isomers (T-CL) is reported using CL from bovine heart mitochondria and thiyl radicals generated by UV-photolysis from 2-mercaptoethanol. Analytical approaches for CL isomer separation and identification via ¹H/¹³C NMR are provided, together with the chemical study of CL derivatization to fatty acid methyl esters (FAME), useful for lipidomics and metabolomics research. Kinetics information of the radical chain isomerization process was obtained using γ-irradiation conditions. The CL isomerization affected the structural organization of membranes, as tested by the reduction in unilamellar liposome diameter, and accompanied the well-known process of oxidative consumption induced by Fenton reagents. These results highlight a potential new molecular modification pathway of mitochondrial lipids with wide applications to membrane functions and biological consequences. Full article

Curcumin is a natural polyphenol with strong antioxidant activity. However, this molecule shows a very poor bioavailability, instability, and rapid metabolism in vivo. In this work curcumin was loaded in Eudragit-coated liposomes to create a gastroresistant carrier, able to protect its load from degradation and free it at the site of absorption in the colon region. Small unilamellar vesicles were prepared and coated with Eudragit by a pH-driven method. The physico-chemical properties of the prepared systems were assessed by light scattering, transmission electron microscopy, infrared spectroscopy, and differential scanning calorimetry. The uptake of vesicles by Caco-2 cells and the anti-oxidant activity in cells were evaluated. The produced vesicles showed dimensions of about forty nanometers that after covering with Eudragit resulted to have micrometric dimensions at acid pH. The experiments showed that at pH > 7.0 the polymeric coating dissolves, releasing the nanometric liposomes and allowing them to enter Caco-2 cells. Delivered curcumin loaded vesicles were then able to decrease significantly ROS levels as induced by H₂O₂ in Caco-2 cells. The proposed work showed the possibility of realizing effective gastroresistant curcumin liposome formulations for the delivery of antioxidant molecules to Caco-2 cells, potentially applicable to the treatment of pathological conditions related to intestinal oxidative stress. Full article

Mitochondria are membrane-enclosed organelles present in most eukaryotic cells, described as “power houses of the cell”. The mitochondria can be a target for inducing cancer cell death and for developing strategies to bypass multi drug resistance (MDR) mechanisms. 4-Carboxybutyl triphenylphosphonium bromide-polyethylene glycol-distearoylphosphatidylethanolamine (TPP-DSPE-PEG) and dequalinium-polyethylene glycol-distearoylphosphatidylethanolamine (DQA-DSPE-PEG) were synthesized as mitochondriotropic molecules. Mitochondria-targeting liposomes carrying resveratrol were constructed by modifying the liposome’s surface with TPP-PEG or DQA-PEG, resulting in TLS (Res) and DLS (Res), respectively, with the aim to obtain longer blood circulation and enhanced permeability and retention (EPR). Both TLS (Res) and DLS (Res) showed dimensions of approximately 120 nm and a slightly positive zeta potential. The enhanced cellular uptake and selective accumulation of TLS (Res) and DLS (Res) into the mitochondria were demonstrated by behavioral observation of rhodamine-labeled TLS or DLS, using confocal microscopy, and by resveratrol quantification in the intracellular organelle, using LC–MS/MS. Furthermore, TLS (Res) and DLS (Res) induced cytotoxicity of cancer cells by generating reactive oxygen species (ROS) and by dissipating the mitochondrial membrane potential. Our results demonstrated that TLS (Res) and DLS (Res) could provide a potential strategy to treat cancers by mitochondrial targeting delivery of therapeutics and stimulation of the mitochondrial signaling pathway. Full article

Anisotropic assembly of nanoparticles (NPs) has attracted extensive attention because of the potential applications in materials science, biology, and medicine. However, assembly control (e.g., the number of assembled NPs) has not been adequately studied. Here, the growth of anisotropic gold NP assemblies on a liposome surface is reported. Citrate-coated gold NPs adsorbed on liposome surfaces were assembled in one dimension at temperatures above the phase transition temperature of the lipid bilayer. Growth of the anisotropic assemblies depended on the heating time. Absorption spectroscopy and transmission electron microscopy revealed that the gradual growth was attributed to liposome fusion, which was strongly affected by the size of the gold NPs. This method enabled us to precisely control the number of NPs in each anisotropic assembly. These results will enable the fabrication of functional materials based on NP assemblies and enable investigations of cell functions and disease causality. Full article