Search Results (484)

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article

Background/Objectives: As novel synergistic strategy for heart failure (HF), this study explores the formulation and characterization of liposomal systems co-loaded with SGLT2 inhibitors (dapagliflozin—DAPA and empagliflozin—EMPA) and curcumin (Cur). Methods: To enhance liposomal membrane stability and achieve sustained, controlled drug release, oleanolic acid (OA) was incorporated into the lipid bilayer, while the liposomal surface was coated with polyvinylpyrrolidone (PVP). Results: The resulting liposomes exhibited favorable physico-chemical properties (particle size ~170 nm, low PDI, negative zeta potential), high encapsulation efficiencies (up to 97%), and spherical morphology as confirmed by STEM. XRD and DSC analyses indicated successful API incorporation and amorphization within the lipid matrix, while PVP coating provided slight improvements in thermal stability. Trehalose proved to be an effective cryoprotectant, preserving liposome integrity after freeze-drying. In vitro release studies demonstrated sustained and delayed drug release, especially in PVP-coated and OA-containing formulations. Conclusions: All these findings highlight the promise of PVP-coated, OA-stabilized liposomal formulations co-loaded with SGLT2 inhibitors and Cur as biocompatible, multifunctional platforms for targeted HF therapy. Full article

Nanocarriers have found numerous applications in pharmaceutical and food sectors due to their unique physical and chemical properties. In particular, liposomes are the most extensively studied kind of nanoparticles for these applications. They are spherical colloidal systems characterized by lipid membranes enclosing an aqueous core. This versatile structure enables the incorporation of hydrophilic, hydrophobic, and amphiphilic molecules, making them optimal candidates for the controlled release of drugs and enzymes. Despite numerous promising applications, liposomes face challenges such as low colloidal stability, inefficient drug encapsulation, and high production costs for large-scale applications. For this reason, innovative methods, such as microfluidics, electroporation, and supercritical CO₂, are currently being investigated to overcome these limitations. This review examines the recent applications of liposomes in enzyme encapsulation within the pharmaceutical and food sectors, emphasizing production challenges and emerging technological developments. Full article

Background: Mesenchymal stem cells (MSCs) possess an intrinsic tumor-tropic ability, and therefore, MSCs may potentially be used as biomimetic carriers for active drug delivery systems targeting tumors. We previously developed a method to efficiently load liposomes onto the surface of MSCs via electrostatic interactions. The prepared liposome-loaded MSCs (Lip-MSCs) spontaneously accumulated in solid melanoma tumors with low vascular permeability while stably carrying liposomes. Methods: To explore Lip-MSC applications in cancer chemotherapy, doxorubicin (DOX)-encapsulated liposomes (DOX-Lip) were prepared and loaded onto MSCs. The cell viability, DOX-releasing properties, tumor-homing capacity, and anti-tumor efficacy of DOX-Lip-MSCs were analyzed. Results: Small liposomes (100 nm) retained DOX, whereas significant leakage of DOX was observed from 600 nm-sized liposomes. Based on this result, we used 100 nm DOX-Lip for the preparation of DOX-Lip-MSCs. Compared with MSCs loaded with DOX by incubation with DOX solution, DOX-Lip-MSCs could load a larger amount of DOX with minimal cytotoxicity. DOX-Lip-MSCs also showed sustained DOX release. DOX-Lip-MSCs efficiently migrated toward the conditioned medium of B16/BL6 melanoma cells in vitro and accumulated in B16/BL6 tumors in vivo, leading to a significant inhibitory effect on tumor growth. Conclusions: Lip-MSCs can serve as an efficient carrier to deliver anti-cancer drugs into solid tumors. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article

Background and Purpose: Glioblastoma remains a therapeutic challenge with a poor prognosis despite multimodal treatments. Reporter-based magnetic resonance imaging (MRI) offers a promising approach for tumor visualization, but its efficacy depends on sufficient reporter gene expression. This study aimed to develop a chimeric element-regulated ferritin heavy chain 1 (FTH1) reporter system to enhance MRI-based glioma detection while enabling targeted therapy via transferrin receptor (TfR)-mediated drug delivery. Methods: Using gene cloning techniques, we constructed a chimeric FTH1 expression system comprising tumor-specific PEG3 promoter (transcriptional control), bFGF-2 5′UTR (translational enhancement), and WPRE (mRNA stabilization). Lentiviral vectors delivered constructs to U251 glioblastoma cells and xenografts. FTH1/TfR expression was validated by Western blot and immunofluorescence. Iron accumulation was assessed via Prussian blue staining and TEM. MRI evaluated T2 signal changes. Transferrin-modified doxorubicin liposomes (Tf-LPD) were characterized for size and drug loading and tested for cellular uptake and cytotoxicity in vitro. In vivo therapeutic efficacy was assessed in nude mouse models through tumor volume measurement, MR imaging, and histopathology. Results: The chimeric system increased FTH1 expression significantly over PEG3-only controls (p < 0.01), with an increase of nearly 1.5-fold compared to the negative and blank groups and approximately a two-fold increase relative to the single promoter group, with corresponding TfR upregulation. Enhanced iron accumulation reduced T2 relaxation times significantly (p < 0.01), improving MR contrast. Tf-LPD (115 nm, 70% encapsulation) showed TfR-dependent uptake, inducing obvious apoptosis in high-TfR cells compared with that in controls. In vivo, Tf-LPD reduced tumor growth markedly in chimeric-system xenografts versus controls, with concurrent MR signal attenuation. Conclusions: The chimeric regulatory strategy overcomes limitations of single-element systems, demonstrating significant potential for integrated glioma theranostics. Its modular design may be adaptable to other reporter genes and malignancies. Full article

Anthocyanins (ACNs), characterized by their polyhydroxy structures, exhibit high susceptibility to external environmental factors, which significantly limits their application in the food and industrial sectors. To enhance the stability of anthocyanins, anthocyanin nanoliposomes (ACN-NLs) were developed, with encapsulation efficiency, particle size and zeta potential serving as key evaluation parameters. Furthermore, through layer-by-layer self-assembly and electrostatic interactions, ACN-NLs were modified using synanthrin (SY) and pea protein isolate (PPI). Consequently, PPI-modified ACN-NLs (PPI-ACN-NLs) and SY-PPI-modified ACN-NLs (SY-PPI-ACN-NLs) were successfully synthesized. In this study, the structural characteristics of liposomes were investigated using X-ray diffraction (XRD), their in vitro digestibility was evaluated, and their stability under different temperatures, light conditions, and simulated food system conditions was assessed. The results demonstrated that when the mass ratio of soybean lecithin to cholesterol, soybean lecithin to anhydrous ethanol, and drug-to-lipid ratio were set at 5:1, 3:100, and 3:10, respectively, with an ACN concentration of 4 mg/mL, a pea protein solution with pH 3.0, a PPI concentration of 10 mg/mL, and an SY concentration of 8 mg/mL, the prepared ACN-NLs, PPI-ACN-NLs, and SY-PPI-ACN-NLs exhibited optimal performance. Their respective encapsulation efficiencies were 52.59 ± 0.24%, 83.80 ± 0.43%, and 90.38 ± 0.24%; average particle sizes were 134.60 ± 0.76 nm, 213.20 ± 0.41 nm, and 246.60 ± 0.24 nm zeta potentials were −32.4 ± 0.75 mV, −27.46 ± 0.69 mV, and −16.93 ± 0.31 mV. The changes in peak shape observed via X-ray diffraction (XRD), in vitro digestion profiles, and alterations in anthocyanin release rates under different conditions collectively indicated that the modification of ACN-NLs using SY and PPI enhanced the protective effect on the ACNs, improving their biological activity, and providing a robust foundation for the practical application of ACNs. Full article

Background: The active (remote) loading of drugs into nanoparticulate systems via the pH gradient technique has been proven highly successful in liposomes, as numerous formulations have reached the market. However, this is not the case for niosomes, as the full potential of this area remains largely undiscovered. The purpose of this research is to study the effect of different co-surfactants (Cremophor RH 40, Cremophor ELP and Solutol HS-15) on stabilising the niosomal membrane to enable the creation of a pH gradient. Methods: For visualisation of pH gradients, pH indicator bromocresol green (BCG) was used as a novel encapsulated model molecule to visually investigate the ability of niosomes to entrap drugs through active loading. Thereafter, the optimised BCG niosomal formulation was applied to encapsulate a therapeutic drug molecule, doxorubicin, via pH gradient active loading. Niosomes were formulated via thin-film hydration using Span 60, cholesterol, with or without co-surfactants. Thin films were hydrated with either Trizma buffer or HEPES buffer for BCG, or ammonium sulfate for doxorubicin. The niosomes’ outer membrane pH was adjusted via either the addition of HCl or citric acid in the case of BCG, or by passing the niosomes through a Sephadex G50 gel column, pre-equilibrated with PBS or Trizma buffer, in the case of doxorubicin. Results: Niosomes formulated with Span 60 and cholesterol could not be formed at acidic pH and thus could not create a pH gradient. All three co-surfactants, when added to Span 60 and cholesterol, stabilised the niosomes and enabled them to form a pH gradient. Niosomes (after size reduction) containing Solutol HS-15 showed significantly higher entrapment efficiency of BCG when compared to Cremophor RH 40 and Cremophor ELP (67.86% vs. 15.57% vs. 17.81%, respectively, with sizes of 159.6 nm, 177.9 nm and 219.1 nm, respectively). The use of HEPES buffer resulted in a higher EE of BCG compared to Trizma buffer (72.85% vs. 67.86%) and achieved a size of 283.4 nm. The Solutol HS-15 containing formulation has exhibited 68.28% EE of doxorubicin with ammonium sulfate as the inner buffer, while the external buffer was Trizma with a size of 241.1 nm after extrusion. Conclusions: Niosomal formulations containing Solutol HS-15 are highly promising for remote drug loading. The novel use of BCG for studying pH gradient and drug loading into niosomes has proved beneficial and successful. Full article

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

Background/Objectives: Jaspine B, a synthetic analog of anhydrophytosphingosine, demonstrates significant anticancer activity; however, its clinical application is hindered by its poor oral bioavailability, resulting in suboptimal systemic exposure. This study aimed to enhance the pharmacokinetic properties of Jaspine B by developing a liposomal delivery system. Methods: Jaspine B-loaded liposomes were formulated using a microfluidic approach and characterized by transmission electron microscopy (TEM) to assess particle morphology and size distribution. A sensitive and selective LC-MS/MS assay was developed and fully validated to quantify Jaspine B in rat plasma. The assay revealed excellent linearity across a broad concentration range and high intra- and inter-day precision. A pharmacokinetic study was conducted in Sprague Dawley rats to evaluate the influence of liposomal encapsulation on the pharmacokinetic profile of Jaspine B. Results: The liposomal formulation accelerated the absorption of Jaspine B, reaching the maximum concentration (T_max) at 2 h as opposed to 6 h in plain Jaspine B. The half-life (t_1/2) increased significantly from 7.9 ± 2.3 h to 26.7 ± 7.3 h. The area under the curve (AUC_0–∞) increased over two-fold from 56.8 ± 12.3 ng.h/mL to 139.7 ± 27.2 ng.h/mL, suggesting increased systemic drug exposure. Similarly, the drug molecule’s mean residence time (MRT) increased over three-fold. Conclusions: These results indicate that liposomal formulation enhances the pharmacokinetics of Jaspine B, prolonging its body circulation and exposure, which explains the improved therapeutic outcomes we observed in our previous pharmacodynamic study. Full article

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article

Background: Glioblastoma (GBM) is a highly aggressive primary brain tumor with limited therapeutic options, particularly due to the limited blood–brain barrier (BBB) permeability. Nanoparticle-based drug delivery systems, such as liposomes, can prolong drugs’ circulation time and enhance their accumulation within brain tumors, thereby improving therapeutic outcomes. Controlled drug release further contributes to high local drug concentrations while minimizing systemic toxicity. Oleic acid (OA), a monounsaturated fatty acid, is commonly used to enhance drug loading and increase lipid membrane fluidity. In this study, we developed liposomal formulations with optimized temozolomide (TMZ)’s loading and analyze its response to focused ultrasound (FUS). Methods: We synthetized OA-based liposomes with different lipid composition, performed physicochemical characterization (DLS, TEM) and analyzed the TMZ loading efficiency. Different FUS parameters were tested for effective OA-based liposomes destruction. Safety of selected parameters was evaluated in vivo by MRI, histological staining and RT-PCR of pro-inflammatory cytokines. Results: All the formulations exhibited comparable hydrodynamic diameters; however, OA-containing liposomes demonstrated a significantly higher TMZ encapsulation efficiency and enhanced cytotoxicity in U87 glioma cells. Moreover, it was shown that OA-liposomes were disrupted at lower acoustic pressures (5 MPa), while conventional liposomes required higher thresholds (>8 MPa). A safety analysis of FUS parameters indicated that pressures exceeding 11 MPa induced brain edema, necrotic lesions and elevated cytokine levels within 72 h post-treatment. Conclusions: These results suggest that OA-based liposomes possess favorable characteristics, with an increased sonosensitivity for the site-specific delivery of TMZ, offering a promising strategy for glioma treatment. Full article

A new method of the design of stimuli-sensitive multiliposomal containers for encapsulation and controlled drug release is described. Despite quite a wide choice of pH-sensitive containers, there is still a considerable challenge to synthesize those that respond quickly to small variations in pH and release most of the encapsulated drug in a short time. The suggested AMS-containing multiliposomal complexes demonstrated an excellent rate of encapsulated substance release under altering the pH of the outer solution. To improve the efficiency of the delivery of bioactive compounds to target cells and to increase the therapeutic effect, pH-sensitive liposomes were concentrated on the surface of the carrier- PEG-coated cationic liposomes. A pH-sensitive ampholytic derivative of cholan-24-oic acid embedded into the membrane of anionic liposomes allowed the rapid release of the cargo in the areas of low pH, such as tumors, inflammation sites, etc. The diameter of the complexes was optimized for passive targeting and typically ranged from 250 to 400 nm. The biodegradability of liposomes ensured enzymatic destruction of the multiliposomal containers and their elimination from the body after performing their transport function. The multiliposomal complexes and products of their biodegradation demonstrated low cytotoxicity. The composition of multiliposomal complexes, in particular, the amount of PEGylated lipid in the bilayer, was estimated to provide a high speed of the cargo release upon changing the pH. The novel developed pH-sensitive containers show potential for biomedical applications. Full article

Accurate diagnosis of diseases in patients is crucial, particularly in older individuals, where the focus is often placed primarily on advanced age and its associated symptoms. However, advancements in technology and research have revealed that certain diseases traditionally linked to aging can also manifest in younger populations, demonstrating similar bodily changes. One such condition is sarcopenia, a degenerative disease of skeletal muscle that arises from various pathological processes affecting the tissues. In this study, we developed a liposomal formulation based on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), in which both nicotinamide mononucleotide (NMN) and Matrigel (Mgel) were co-encapsulated, each playing a distinct role in the management of sarcopenia. NMN is known to stimulate the increase of NAD+ levels, while Matrigel enhances the activity of satellite cells, thereby facilitating muscle fiber regeneration and stabilizing protein levels. Results from the DLS, SEM, and TEM analyses revealed significant differences attributed to the type of therapeutic agent used and the synthesis parameters. Additionally, the drug release profile underscored the complementary nature and significance of selecting the appropriate active substances for effective treatment strategies. The in vitro investigations aimed to assess the potential of DMPC lipid vesicles loaded with NMN, either alone or in combination with Matrigel, to counteract sarcopenia-associated oxidative stress and mitochondrial dysfunction. The results showed that both NMN-based formulations reduced oxidative damage, preserved mitochondrial function, and maintained cytoskeletal integrity in a hydrogen peroxide-induced model of sarcopenia. Importantly, the formulation containing both NMN and Matrigel demonstrated superior protective effects, suggesting a synergistic role of the extracellular matrix components in enhancing muscle cell resilience. These findings support the use of DMPC-based delivery systems as promising candidates for sarcopenia therapy and warrant further investigation into their mechanisms of action in preventing muscle cell degeneration. Full article

In the present study, we developed a moxifloxacin (MXF)-encapsulated liposome-enriched alginate nanocomposite hydrogel coating. MXF was encapsulated in soy lecithin (SL:MXF:2:1) via the probe sonication method with an average efficiency of 80%. Two different manufacturing methods, including a micropipetting and a T-shaped microfluidic junction (TMJ) device technique, were used to incorporate the MXF-encapsulated liposomes into hydrogel matrices and layered as a coating on polymeric substrate material. Drug encapsulation and its incorporation into the hydrogel matrix significantly enhanced its stability and facilitated a prolonged drug release profile. A relatively rapid drug release was observed in the MXF-encapsulated liposome-loaded polymeric particulate layer developed via the micropipetting than the TMJ device technique. The findings confirmed sustained drug release behavior due to a hydrogel particulate structural uniformity conferred by the micromachine device, TMJ. Thus, these nanocomposite hydrogel coatings achieved can serve as a promising candidate for the treatment of ophthalmic or mucosal membrane infections. Full article