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Aim: This study aimed to construct an ischemic cardiomyocyte-targeted and ROS-responsive drug release system to reduce myocardial ischemia-reperfusion injury (MI/RI). Methods: We constructed thioketal (TK) and cardiac homing peptide (CHP) dual-modified liposomes loaded with puerarin (PUE@TK/CHP-L), which were expected to deliver drugs precisely into ischemic cardiomyocytes and release drugs in response to the presence of high intracellular ROS levels. The advantages of PUE@TK/CHP-L were assessed by cellular pharmacodynamics, in vivo fluorescence imaging and animal pharmacodynamics. Results: PUE@TK/CHP-L significantly inhibited apoptosis and ferroptosis in H/R-injured cardiomyocytes and also actively targeted ischemic myocardium. Based on these advantages, PUE@TK/CHP-L could significantly enhance the drug's ability to attenuate MI/RI. Conclusion: PUE@TK/CHP-L had potential clinical value in the precise treatment of MI/RI. Article highlights Myocardial ischemia-reperfusion injury (MI/RI) is a series of pathological changes caused by revascularisation after myocardial infarction, for which there is no effective treatment. Excessive production of reactive oxygen species (ROS) is an important predisposing factor for MI/RI. Apoptosis and ferroptosis of cardiomyocytes are important pathological mechanisms of myocardial ischemia-reperfusion injury and both are closely related to excessive intracellular ROS. We have successfully synthesized ROS-responsive and cardiac-targeted liposomes loaded with puerarin (PUE@TK/CHP-L). It was found that PUE@TK/CHP-L could target ischemic myocardium. In vivo and ex vivo results showed that PUE@TK/CHP-L can effectively reduce the level of myocardial oxidative stress and decrease cardiomyocyte apoptosis and ferroptosis. These results suggested that PUE@TK/CHP-L could hopefully be a promising drug carrier for mitigating MI/RI. [ABSTRACT FROM AUTHOR]

Olea europaea L. (Oleaceae), is rich in phenolic content and has powerful antioxidant and antidiabetic activity. However, there are no medicinal products prepared due to this feature. Therefore, this study aims to characterize an O. europaea extract with strong antioxidant and antidiabetic properties and to prepare nanoformulations containing this extract. To determine the activities of the extracts prepared from the leaves of the plant, DPPH• and ABTS•+ scavenging, Fe+3 reducing activity, α-amylase, and α-glucosidase inhibition assays were performed. The oleuropein content of the absolute ethanol extract with the highest activity was analysed by HPLC. The characterized extract was loaded into liposomes and chitosan coated liposomes, and the long-term sustainability of their activity was investigated. The encapsulation efficiency was 65.2% for the liposome and 66.8% for the chitosan-coated liposome formulation. The amounts of the extracts released from the formulations were evaluated to exhibit antioxidant and antidiabetic activity. [ABSTRACT FROM AUTHOR]

Aim: To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. Methods: Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. Results: SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of −23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. Conclusion: SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1β, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Encapsulation efficiency (EE), structure, antioxidant and antimicrobial activities of liposomes loaded with chitooligosaccharide–gallic acid conjugate (COS–GAL) as affected by cholesterol (CHO) and ascorbyl palmitate (AP) as stabilisers were investigated. In addition, release kinetics and in vitro digestion of selected liposomes were also studied. The higher EE was obtained for liposome (AP/COS–GAL) stabilised by 0.50% AP, when used to encapsulate 0.10% COS–GAL conjugate. The highest EE was noticed for 0.25% CHO when used to encapsulate 1.00% conjugate (CHO/COS–GAL) as compared to the counterparts (P < 0.05). Almost similar antioxidant and antimicrobial activities were noticed for all COS–GAL liposomes and COS–GAL powder. Microstructure study suggested the formation of bilayer in liposomes. CHO/COS–GAL showed a lower release efficiency than the AP/COS–GAL. CHO/COS–GAL was also able to protect conjugate during the in vitro digestion. Therefore, liposomes could be used as a promising carrier of COS–GAL conjugate in both foods as well as medical systems. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative magnetization transfer (qMT) models aim to quantify the contributions of lipids and macromolecules to the MRI signal. Hence, a model system that relates qMT parameters and their molecular sources may improve the interpretation of the qMT parameters. Here we used membrane lipid phantoms as a meaningful tool to study qMT models. By controlling the fraction and type of membrane lipids, we could test the accuracy, reliability, and interpretability of different qMT models. Methods: We formulated liposomes with various lipid types and water‐to‐lipids fractions and measured their signals with spoiled gradient‐echo MT. We fitted three known qMT models and estimated six parameters for every model. We tested the accuracy and reproducibility of the models and compared the dependency among the qMT parameters. We compared the samples' qMT parameters with their water‐to‐lipid fractions and with a simple MTnorm (= MTon/MToff) calculation. Results: We found that the three qMT models fit the membrane lipids signals well. We also found that the estimated qMT parameters are highly interdependent. Interestingly, the estimated qMT parameters are a function of the membrane lipid type and also highly related to the water‐to‐lipid fraction. Finally, we find that most of the lipid sample's information can be captured using the common and easy to estimate MTnorm analysis. Conclusion: qMT parameters are sensitive to both the water‐to‐lipid fraction and to the lipid type. Estimating the water‐to‐lipid fraction can improve the characterization of membrane lipids' contributions to qMT parameters. Similar characterizations can be obtained using the MTnorm analysis. [ABSTRACT FROM AUTHOR]

AbstractGiant liposomes, or giant unilamellar vesicles (GUVs), have been utilized as cell-size bioreactors to replicate the physical and chemical properties of biological cells. However, conventional methods for preparing GUVs typically lack precise control over their size. Several research groups have recently developed microfluidic techniques to create monodisperse GUVs by generating water-in-oil-in-water (W/O/W) droplets with a thin oil layer that subsequently transform into GUVs. However, the formation of a thin oil shell requires the intricate control of the flow rate, which can be both challenging and unstable. In this study, we investigated the design of a two-step flow-focusing microfluidic channel to produce stable W/O/W droplets. These droplets underwent substantial oil layer reduction through spontaneous removal by fluidic shear forces. Consequently, the majority of the oil layer in the W/O/W droplets was reduced, improving uniformity of GUVs. [ABSTRACT FROM AUTHOR]

Pathogenic serotypes of Vibrio cholerae, transmitted through contaminated water and food, are responsible for outbreaks of cholera, an acute diarrheal disease. While the cholera toxin is the primary virulence factor, V. cholerae also expresses other virulence factors, such as the tripartite toxin MakABE that is secreted via the bacterial flagellum. These three proteins are co-expressed with two accessory proteins, MakC and MakD, whose functions remain unknown. Here, we present the crystal structures of MakC and MakD, revealing that they are similar in both sequence and structure but lack other close structural relatives. Our study further investigates the roles of MakC and MakD, focusing on their impact on the expression and secretion of the components of the MakABE tripartite toxin. Through deletion mutant analysis, we found that individual deletions of makC or makD do not significantly affect MakA expression or secretion. However, the deletion of both makC and makD impairs the expression of MakB, which is directly downstream, and decreases the expression of MakE, which is separated from makCD by two genes. Conversely, MakA, encoded by the makA gene located between makB and makE, is expressed normally but its secretion is impaired. Additionally, our findings indicate that MakC, in contrast to MakD, exhibits strong interactions with other proteins. Furthermore, both MakC and MakD were observed to be localized within the cytosol of the bacterial cell. This study provides new insights into the regulatory mechanisms affecting the Mak protein family in V. cholerae and highlights the complex interplay between gene proximity and protein expression. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a new nicotine transdermal patch: S‐(‐)‐Nicotine‐loaded nano flexible liposome hydrogel patch (S‐(‐)‐Nicotine‐NFL‐HGP), which combined liposome and hydrogel to achieve the long‐lasting and sustained release of S‐(‐)‐Nicotine for the treatment of nicotine withdrawal syndrome (NWS). The S‐(‐)‐Nicotine nanoscale flexible liposomes (S‐(‐)‐Nicotine‐NFL) were prepared using the thin film hydration method, and then combined with a three‐dimensional structured hydrogel to prepare S‐(‐)‐Nicotine‐NFL‐HGP. The initial bond strength (IBS) was (18 ± 2) s, the lasting bond strength (EBS) was (23.5 ± 3.4) s, and the appearance was pale yellow. The cumulative release rate of the patch was 64.8% within 48 h and the Higuchi equation of the drug release process was y = 9.47x1/2−1.13 (R2 = 0.99412). The cumulative transmittance per unit area of the patch after 48 h was (1047 ± 25.0) µg/cm2 and the dermal retention was (35.1 ± 4.2) µg/cm2. The Higuchi equation of the transdermal drug process showed the highest fit in the transdermal experiments with a long‐lasting and sustained release of S‐(‐)‐Nicotine. Stability study results showed that the IBS, EBS, appearance, and the performance of drug release of the patch were almost unchanged within 90 days, which had excellent stability. The patch prepared in this study has potential application prospects. [ABSTRACT FROM AUTHOR]

Objective To elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer (CRC) by using the two-sample and two-step Mendelian randomization (MR) methods, and to explore the mediating role and proportion of immune cells as intermediary factors. Methods The pooled statistical data related to the study were screened, and 179 lipids and CRC were analyzed using two-sample and twostep MR with the inverse variance weighted method. Simultaneously, the causal effect was verified via Bayesian weighted MR. Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits. Sensitivity, heterogeneity, and pleiotropy analyses were performed to verify the reliability of the study results. Results The causal relationship between nine lipid traits and CRC was preliminarily identified, and no reverse causal effect was found (P>0.05). The validity of the results was verified via Bayesian weighted MR (P<0.05). Twenty-seven types of immune cells were suggested to exert a causal effect on CRC. The causal effect of phosphatidylcholine (O-18:2_20:4) on CRC was determined via mediation analysis (OR: 0.8579, 95%CI=0.7395-0.9952, P=0.0429). The CD127-mediated proportion on CD45RA+ CD4+ T cells was 9.14% (β=−0.1052, P=0.0155). Conclusion A causal relationship exists between lipid traits and CRC, and the intervention of CD127 on CD45RA+ CD4+ T cell helps phosphatidylcholine reduce the risk of CRC. [ABSTRACT FROM AUTHOR]

Background: Acrylamide polymers with zwitterionic carboxybetaine (CB) side groups have attracted attention as stealth polymers that do not induce antibodies when conjugated to proteins. However, they induce antibodies when modified onto liposomes. We hypothesized that antibodies are produced against polymer backbones rather than CB side groups. Objectives: In this study, we designed and synthesized a polymer employing CB in its main chain, poly(N-acetic acid-N-methyl-propyleneimine) (PAMPI), and evaluated the blood retention of PAMPI-modified liposomes in mice. Results: The non-fouling nature of PAMPI-modified liposomes estimated from serum protein adsorption was found to be not inferior to PCB- and PEG-modified liposomes. However, to our surprise, the PAMPI-modified liposomes showed an instantaneous clearance less than 1 h post-injection, comparable to the naked liposomes. Conclusions: The extent of the blood retention of polymer-modified liposomes cannot be predicted by their susceptibility to serum protein adsorption and semi-flexible conformation. [ABSTRACT FROM AUTHOR]

There is a growing interest in developing paramagnetic nanoparticles as responsive magnetic resonance imaging (MRI) contrast agents, which feature switchable T1 image contrast of water protons upon biochemical cues for better discerning diseases. However, performing an MRI is pragmatically limited by its cost and availability. Hence, a facile, routine method for measuring the T1 contrast is highly desired in early‐stage development. This work presents a single‐point inversion recovery (IR) nuclear magnetic resonance (NMR) method that can rapidly evaluate T1 contrast change by employing a single, optimized IR pulse sequence that minimizes water signal for "off‐state" nanoparticles and allows for sensitively measuring the signal change with "switch‐on" T1 contrast. Using peptide‐induced liposomal gadopentetic acid (Gd3+‐DTPA) release and redox‐sensitive manganese oxide (MnO2) nanoparticles as a demonstration of generality, this method successfully evaluates the T1 shortening of water protons caused by liposomal Gd3+‐DTPA release and Mn2+ formation from MnO2 reduction. Furthermore, the NMR measurement is highly correlated to T1‐weighted MRI scans, suggesting its feasibility to predict the MRI results at the same field strength. This NMR method can be a low‐cost, time‐saving alternative for pre‐MRI evaluation for a diversity of responsive T1 contrast systems. [ABSTRACT FROM AUTHOR]

This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm−2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment. [ABSTRACT FROM AUTHOR]

AbstractVesicular nanocarriers like niosomes and liposomes are widely researched for controlled drug delivery systems, with niosomes emerging as promising alternatives due to their higher stability and ease of manufacturing. This study aimed to develop and characterize a niosomal formulation for the encapsulation and sustained release of temozolomide (TMZ), a model lipophilic drug, and to compare the stability of niosomes and liposomes, with a particular focus on the behavior of their lipid bilayers. Niosomes were prepared using the thin-film hydration method, composed of Span 60 (Sorbitan monostearate), cholesterol, and soy lecithin in varying molar ratios. The study investigated critical properties such as drug loading capacity, release kinetics, and resistance to enzymatic degradation. The optimized formulation was analyzed for drug entrapment efficiency and stability against phospholipase A2 (PLA2) degradation. The optimized niosomal formulation, with a 4:2:1 molar ratio of Span 60: cholesterol, achieved a high TMZ entrapment efficiency of 73.23 ± 1.02% and demonstrated sustained drug release over 24 hours. In comparison, liposomes released their TMZ payload within 4 hours upon exposure to PLA2, while the niosomes maintained their release profile, indicating superior stability. Spectroscopic and thermal analysis confirmed successful drug encapsulation with no component incompatibilities. [ABSTRACT FROM AUTHOR]

Summary: Eugenol is the main antioxidant and antimicrobial component of essential oils, however, its volatility and water solubility limit its application. In this study, eugenol liposomes (Eug‐Lip) by the ethanol injection method. The average particle size of Eug‐Lip was measured to be between 40 and 70 nm, a polydispersity index (PDI) of 0.2934, a potential between −30 and −60 mV, and an encapsulation rate of 87.12%. The polyvinyl alcohol (PVA)‐based nanofiber membrane (Eug‐Lip‐NF) was prepared by the electrostatic spinning technique. This not only improved the water solubility and stability of eugenol, but also extended its release time and preserved its biological activity. The high‐voltage electric field facilitates the retention of the antioxidant ability of the membrane, as well as the inhibition of both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These results indicate that the combination of liposome and electrostatic spinning technology provides feasibility and promise for eugenol in food and medicine fields. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at "Sotiria" General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS's role in NTM lung disease caused by other species. [ABSTRACT FROM AUTHOR]

Micro- and nano-encapsulation techniques, such as microfluidization, spray drying, and centrifugal extrusion, have been widely utilized in various industries, including pharmaceuticals, food, cosmetics, and agriculture, to improve the stability, shelf life, and bioavailability of active ingredients, such as vitamin A. Emulsion-based delivery platforms offer feasible and appropriate alternatives for safeguarding, encapsulating, and transporting bioactive compounds. Therefore, there is a need to enrich our basic diet to prevent vitamin A deficiency within a population. This review focused on addressing vitamin A shortages, encapsulation techniques for improving the delivery of vital vitamins A and their food applications. Additionally, more studies are required to guarantee the security of nano-delivery strategies, as they proliferate in the food and beverage sector. [ABSTRACT FROM AUTHOR]

Multifunctional nanoplatforms show the synergistic effect of multiple treatment modalities and have become a research hotspot as they are superior to the antitumor properties of single treatment modes. In this work, we synthesized an ∼115 nm liposome nanoparticle ergosterol peroxide/TMP195@liposome (EP/TMP195@lip). It releases the natural product, EP, and the repolarization agent of tumor-associated macrophages, TMP195, through escape of endosomes in breast cancer cells. EP/TMP195@lip could effectively inhibit the proliferation and migration of breast cancer cells and induce mitochondrial membrane potential damage and cell apoptosis by regulating the P53 signaling pathway. Besides, it reshapes the tumor microenvironment, transforming M2-like tumor-associated macrophages (TAMs) into M1-like TAMs to assist the immune cells in recognizing and eliminating tumor tissue. Furthermore, EP/TMP195@lip promotes the maturation and differentiation of dendritic cells and activates T cells, which enhances the effect of tumor immunotherapy. Taken together, EP/TMP195@lip is expected to provide high-quality strategies for safe and effective breast cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Topical eyedrop administration is identified as an ideal non‐invasive strategy for ocular drug delivery. However, multiple complex ocular barriers greatly restrict their effectiveness in the treatment of posterior ocular disease. Herein, a liposome‐based permeable eyedrops (pDrops) capable of overcoming multiple ocular barriers and achieving efficient posterior drug delivery is presented. pDrops have a core‐shell structure in which drugs are encapsulated inside the liposome core with a chitosan shell. This chitosan coating significantly enhances the pDrops' binding to mucin in tears and facilitates the temporary opening of tight junctions in cornea/conjunctive epithelial cells, thereby achieving prolonged preocular retention and enhanced posterior segment drug delivery. In this study, hydrophilic ganciclovir (GCV) and hydrophobic curcumin (CUR) are employed as model drugs. Upon topical instillation, pDrops effectively overcome ocular barriers and delivered GCV to the posterior segment in both rat and rabbit eyes. Notably, CUR delivery by pDrops demonstrates significantly enhanced therapeutic efficacy in light‐damaged retina of mice. Considering that pDrops can deliver both hydrophobic and hydrophilic drugs to the posterior segment of the eye, it can potentially become a feasible platform for the non‐invasive delivery of various drug molecules and improve the treatment efficiency of posterior ocular diseases. [ABSTRACT FROM AUTHOR]

AbstractNaringenin may play a role in browning by increasing thermogenic gene expression. In this study, we encapsulated naringenin using a liposomal formulation and examined the effects of both free and liposomal naringenin on white adipose tissue browning in C57BL6/J mice. In the first phase of the study, naringenin was encapsulated by the liposome method, which is biocompatible and biodegradable. The physical and chemical properties of liposomal naringenin were tested. In the second phase, a total of 48 six-week-old mice were divided into two main groups: prevention and recovery. Each main group was divided into four subgroups: nano-naringenin, void, free-naringenin, and control. The prevention group received a high-fat diet for 10 weeks along with weekly intravenous injections of 20 µM naringenin. On the other hand, the recovery group was first subjected to a high-fat diet for 10 weeks, followed by an additional 10 weeks of the same diet, along with weekly intravenous injections of 20 µM naringenin. Body weight was measured once per week, and brown adipose tissue, inguinal white adipose tissue, and serum samples were collected from each mouse. The mean particle size, polydispersity index and zeta potential values of liposomal naringenin were ∼207 nm, 0.35, and −27 mV, respectively. The encapsulation and loading efficiencies of liposomal naringenin were 94.6 and 19.2%, respectively. Liposomal naringenin exhibited sustained-release behavior, while free naringenin showed a burst-release profile. Liposomal naringenin showed the best physical stability in light and at 4 °C, while free naringenin was more chemically stable in light and at 4 and 22 °C. Free and liposomal naringenin did not significantly reduce weight gain. In the prevention group, liposomal naringenin increased PRDM16 gene expression in inguinal white adipose tissue 4.29 times more than free naringenin (p = 0.010). However, neither formulation significantly altered the expression levels of other browning or adipogenesis markers in the tissues. The results suggest that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Further research is needed to better understand the physiological effects of liposomal naringenin. [ABSTRACT FROM AUTHOR]

Photoswitchable lipids, particularly azobenzene‐derivatized phosphatidylcholine (azoPC) lipids, offer a unique mechanism for reversible modification of membrane properties upon exposure to ultraviolet (UV) radiation. Through all‐atom molecular dynamics simulations, we explore how UV irradiation‐induced trans‐to‐cis photoisomerization (TCPI) of AzoPC lipid influences the structure and dynamics of a lipid membrane, composed of dipalmitoylphosphatidylcholine (DPPC) and cholesterol with similar composition to that of the DOXIL®. Structural and dynamical analyses of two states of the membrane, 'dark' state (containing cis‐azoPC lipid) and 'bright' state (containing 85 % cis‐azoPC and 15 % trans‐azoPC lipids) reveal that the TCPI reduces membrane packing density and increases diffusivity of lipids. We have demonstrated an enhanced intercalation of doxorubicin (DOX), an anticancer drug, in the 'bright' state of the membrane compared to that in the 'dark' state. This study – elucidating the complex interplay between lipid composition, photoswitching, and lipid‐drug interactions – contributes to the design of lipid‐based systems for targeted drug delivery and biomedical applications. [ABSTRACT FROM AUTHOR]

AbstractSkin cancer poses a significant global health concern necessitating innovative treatment approaches. This review explores the potential of vesicle nanoformulation incorporating EA (edge activators) to overcome barriers in skin cancer management. The skin's inherent protective mechanisms, specifically the outermost layer called the stratum corneum and the network of blood arteries, impede the permeation of drugs. Phospholipid-enriched EA based nanoformulation offer a promising solution by enhancing drug penetration through skin barriers. EAs like Span 80, Span 20, Tween 20, and sodium cholate etc., enhance vesicles deformability, influencing drug permeation. This review discusses topical application of drugs treat skin cancer, highlighting challenges connected with the conventional liposome and the significance of using EA-based nanoformulation in overcoming these challenges. Furthermore, it provides insights into various EA characteristics, critical insights, clinical trials, and patents. The review also offers a concise overview of composition, preparation techniques, and the application of EA-based nanoformulation such as transfersomes, transliposomes, transethosomes, and transniosomes for delivering drugs to treat skin cancer. Overall, this review intends to accelerate the development of formulations that incorporate EA, which would further improve topical drug delivery and enhance therapeutic outcomes in skin cancer treatment. [ABSTRACT FROM AUTHOR]

The exploration of cell‐based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one‐step fusion process. We demonstrate doxorubicin (DOX)‐encapsulated liposomes conjugated with interleukin‐15 (IL‐15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus (Mab) is an opportunistic nontuberculous mycobacterium responsible of difficult-to-treat pulmonary infections in vulnerable patients, such as those suffering from Cystic Fibrosis (CF), where it represents a major cause of morbidity and mortality. Additionally, due to the intrinsic extensive antimicrobial resistance spectrum displayed by this species and the side effects reported for some available antibiotics, the therapeutic management of such infections remains extremely difficult. In the present study, we show that phosphatidylserine liposomes (PS-L) enhance intracellular mycobacterial killing of Mab infected human macrophages with functional or pharmacologically inhibited cystic fibrosis conductance regulator (CFTR), by a mechanism involving phagosome acidification and reactive oxygen species (ROS) production. Additionally, PS-L significantly reduce proinflammatory response of Mab infected macrophages in terms of NF-kB activation and TNF-α production, irrespective of CFTR inhibition. Altogether, these results represent the proof of concept for a possible future development of PS-L as a therapeutic strategy against difficult-to-treat Mab infection. [ABSTRACT FROM AUTHOR]

In the process of the drug development, studies on the cytochrome P450 (CYP) profiles after its administration provided fundamental information regarding drug interactions with concomitantly administered drugs. Here, we evaluated the influence of the administration of H12-(ADP)-liposomes, a platelet substitute, on the mRNA and protein expression, and metabolic activity of CYPs, with focus on the CYP1A2, CYP2C11 and CYP3A2, in rat liver. At 24 h after administering saline or H12-(ADP)-liposomes (10 mg of lipids/kg), a quantitative RT-PCR and western blot analysis revealed that the mRNA and proteins expression of all of the target hepatic CYP isoforms were not different between the saline and H12-(ADP)-liposome groups. Furthermore, an ex vivo CYP metabolic activity assay showed that hepatic CYP metabolic activities in the H12-(ADP)-liposome group were comparable to the corresponding saline group. On the other hand, the area under the blood concentration-time curve for substitutes for CYP1A2 and CYP2C11 was higher in H12-(ADP)-liposome group than in saline group, but the degree of elevations was negligible levels. At a minimum, based on these results, we conclude that H12-(ADP)-liposomes have no quantitative and qualitative effect on the hepatic CYP isoforms, indicating that the drug interactions of H12-(ADP)-liposomes with CYP-metabolizing drugs would be negligible. [ABSTRACT FROM AUTHOR]

Herein a split‐type photoelectrochemical (PEC) immunosensor based on in situ grown gold nanoparticles (Au NPs) on the surface of ZnO microrods (ZnO MRs) was devised for the detection of alpha‐fetoprotein (AFP) by employing dopamine (DA)‐loaded liposomes as the signal amplification strategy. Specifically, as the level of AFP rises, a proportional number of sandwich‐type immunocomplexes form in the well of the microplate, which can introduce a corresponding amount of DA‐encapsulated liposomes at the same time. Encapsulated DA molecules will be released with the stimulation of Triton X‐100, thereby resulting in the marked enhancement of the PEC signal. Under optimized conditions, the proposed PEC immunosensing platform displays specific photocurrent responses toward AFP in a broad dynamic working range of 0.05 −50 ng mL−1, achieving an impressively low limit of detection (LOD) of 18.7 pg mL−1. Furthermore, this methodology not only displays high specificity, and satisfactory storage stability but also ensures acceptable accuracy and practicality for the analytical applications of human serum samples. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer metastasis remains the primary cause of mortality among women globally. Targeted therapies have revolutionized treatment efficacy, with Trastuzumab (Trast), a monoclonal antibody, targeting HER2-positive advanced breast cancer. The tumor-homing peptide iRGD enhances the intratumoral accumulation and penetration of therapeutic agents. Liposomes serve as versatile nanocarriers for both hydrophilic and hydrophobic drugs. Gefitinib (GFB) is a potential anticancer drug against HER2-positive breast cancer, while Lycorine hydrochloride (LCH) is a natural compound with anticancer and anti-inflammatory properties. This study developed TPGS-COOH-coated liposomes co-loaded with GFB and LCH, prepared by the solvent injection method, and surface-functionalized with Trast and iRGD. The dual surface-decorated liposomes (DSDLs) were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), surface chemistry, surface morphology, and their crystallinity during in-vitro drug release, drug encapsulation, and in-vitro cell line studies on SK-BR-3 and MDA-MB-231 breast cancer cells. The half-maximum inhibitory concentration (IC-50) values of single decorated liposomes (SDLs), iRGD-LP, and Trast-LP, as well as DSDLs (iRGD-Trast-LP) on SK-BR-3 cells, were 6.10 ± 0.42, 4.98 ± 0.36, and 4.34 ± 0.32 μg/mL, respectively. Moreover, the IC-50 values of SDLs and DSDLs on MDA-MB-231 cells were 15.12 ± 0.68, 13.09 ± 0.59, and 11.08 ± 0.48 μg/mL, respectively. Cellular uptake studies using confocal laser scanning microscopy (CLSM) showed that iRGD and Trast functionalization significantly enhanced cellular uptake in both cell lines. The wound-healing assay demonstrated a significant reduction in SDL and DSDL-treated MDA-MB-231 cell migration compared to the control. Additionally, the blood compatibility study showed minimal hemolysis (less than 5% RBC lysis), indicating good biocompatibility and biosafety. Overall, these findings suggest that TPGS-COOH-coated, GFB and LCH co-loaded, dual-ligand (iRGD and Trast) functionalized, multifunctional liposomes could be a promising therapeutic strategy for treating HER2-positive metastatic breast cancer. [ABSTRACT FROM AUTHOR]

The spectral and bactericidal properties of a number of biodyes including bromophenol blue, amido black 10B, methyl thymol blue, basic fuchsin, chrome dark blue, eosin, indigo dye, and bromophenol red have been characterized. The inclusion of eosin, bromophenol red, indigo, and rifampicin into the internal space of phospholipid nanocontainers was shown to lead to leveling of the characteristic absorption maxima in the visible and ultraviolet regions of the spectra of these compounds taken in aqueous solution. This effect allows visual and spectrophotometric monitoring of the prodrug incorporation into liposomes. The construction of a number of supramolecular forms of prodrugs, which are micelles and liposomes derived from modifications of the bactericidal nucleoside brivudine in various combinations, showed the feasibility of using indigo as a dye marker. This permits the identification of liposomes formed from an equimolar mixture of dimyristoylphosphatidylbrivudine lipoconjugate with dimyristoylphosphatidylcholine as a potential prodrug formulation that most effectively inhibits the growth of Staphylococcus aureus cells. [ABSTRACT FROM AUTHOR]

The solid tumors provide a series of biological barriers in cellular microenvironment for designing drug delivery methods based on advanced stimuli-responsive materials. These intertumoral and intratumoral barriers consist of perforated endotheliums, tumor cell crowding, vascularity, lymphatic drainage blocking effect, extracellular matrix (ECM) proteins, hypoxia, and acidosis. Triggering opportunities have been drawn for solid tumor therapies based on single and dual stimuli-responsive drug delivery systems (DDSs) that not only improved drug targeting in deeper sites of the tumor microenvironments, but also facilitated the antitumor drug release efficiency. Single and dual stimuli-responsive materials which are known for their lowest side effects can be categorized in 17 main groups which involve to internal and external stimuli anticancer drug carriers in proportion to microenvironments of targeted solid tumors. Development of such drug carriers can circumvent barriers in clinical trial studies based on their superior capabilities in penetrating into more inaccessible sites of the tumor tissues. In recent designs, key characteristics of these DDSs such as fast response to intracellular and extracellular factors, effective cytotoxicity with minimum side effect, efficient permeability, and rate and location of drug release have been discussed as core concerns of designing paradigms of these materials. [ABSTRACT FROM AUTHOR]

Background: Nuciferine (NUC), a natural compound extracted from lotus leaves, has been proven to have anti‐obesity effects. However, the development and application of NUC as an anti‐obesity drug in dogs are hindered due to its poor water solubility and low bioavailability. Objective: To promote the development of NUC‐related products for anti‐obesity in dogs, this study prepared NUC into a liposome formulation and evaluated its characteristics, pharmacokinetics in dogs, and anti‐obesity effects on high‐fat diet dogs. Methods: NUC liposomes were prepared by the ethanol injection method, using NUC, egg lecithin, and β‐sitosterol as raw materials. The characteristics and release rate in vitro of liposomes were evaluated by particle size analyser and dialysis method, respectively. The pharmacokinetics in dogs after oral administration of NUC‐liposomes was carried out by the high‐performance liquid chromatography (HPLC) method. Moreover, we investigated the anti‐obesity effect of NUC‐liposomes on obese dogs fed with a high‐fat diet. Results: NUC‐liposome was successfully prepared, with an EE of (79.31 ± 1.06)%, a particle size of (81.25 ± 3.14) nm, a zeta potential of (–18.75 ± 0.23) mV, and a PDI of 0.175 ± 0.031. The cumulative release rate in vitro of NUC from NUC‐liposomes was slower than that of NUC. The T1/2 and relative bioavailability of NUC‐liposomes in dogs increased, and CL reduced compared with NUC. In addition, the preventive effect of NUC‐liposomes on obesity in high‐fat diet dogs is stronger than that of NUC. Conclusions: The liposome formulation of NUC was conducive to improve its relative bioavailability and anti‐obesity effect in dogs. [ABSTRACT FROM AUTHOR]

Liposomes are widely used for smart delivery due to their biodegradability and biocompatibility. Recently, liposomes have been developed to respond to dual and multi-stimuli. This development leads to the potential for superior in vitro and in vivo drug delivery in the future. In this study, egg PC liposomes responsive to temperature, oxidation, and NIR irradiation were prepared by modifying the liposomal membranes with poly(hydroxyethyl acrylate-co-ethyl vinyl sulfide) (P(HEA-co-EVS)) and including indocyanine green (ICG) in the liposomes.The copolymer was found to exhibit a lower critical solution temperature (LCST) and it was oxidizable and surface-active.On the TEM photos of the liposomes, multi-lamellar vesicles were found and the size was in accordance with the hydrodynamic diameter. The liposomes released their payload in response to H2O2 concentration possibly because the EVS was oxidized by the oxidizing agent. The liposome exhibited a temperature-responsive release possibly due to the thermal contraction of the copolymer chains.In addition, the release was triggered when a near-infrared(NIR) laser was irradiated to the liposome suspensions. Under NIR irradiation, the photosensitizer (i.e. ICG) can generate heat and reactive oxygen species, which, in turn, would induce the conformational and polarity change of the polymer chains, leading to a release. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, −7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects. [Display omitted] • These hybrid vesicles improved storage stability for cargos, follicle retention, and drug encapsulation efficiency (EE%) for finasteride. • The Hybrid/Au@Fi (115.07 ± 0.32 nm, −7.50 ± 1.68 mV) facilitated simulated in vitro layered dermal papilla cell (DPC) migration and angiogenesis with favorable cell dynamic behavior and no cytotoxicity. • In an AGA mouse model, once-daily topical application of Hybrid/Au@Fi gel exhibited a faster transition of hair follicles from the catagen to the anagen, higher hair regrowth coverage, and improved quality of regrowth hair, compared to once-daily 5% minoxidil treatment. [ABSTRACT FROM AUTHOR]

Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co -loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

Brain-targeted drug delivery poses a great challenge due to the blood-brain barrier (BBB). In a previous study, we have developed a peptide-modified stealth liposome (SP-sLip) to enhance BBB penetration via the adsorption of apolipoproteins in plasma. SP is an 11-amino acid peptide derived from 25 to 35 of the Amyloid β peptide (Aβ 1–42), which is a nature ligand of apolipoproteins. Although freshly prepared SP-sLip exhibited efficient brain targeting performance, it occured self-aggregation and instability in storage. In this study, we developed a D-peptide ligand according to the reverse sequence of SP with D-amino acids, known as DSP, to improve the stability in storage. Notably, DSP exhibited a reduced tendency for self-aggregation and improved stability in comparison to the SP peptide. Furthermore, compared to SP-sLip, DSP-modified sLip (DSP-sLip) demonstrated enhanced stability (>2 weeks), prolonged blood circulation (AUC increased 44.4%), reduced liver and spleen accumulation (reduced by 2.23 times and 1.86 times) with comparable brain-targeting efficiency. Similar to SP-sLip, DSP-sLip selectively adsorbed apolipoprotein A1, E, and J in the blood to form functionalized protein corona, thus crossing BBB via apolipoprotein receptor-mediated transcytosis. These findings underscored the importance of ligand stability in the in vitro and in vivo performance of brain-targeted liposomes, therefore paving the way for the design and optimization of efficient and stable nanocarriers. DSP-sLip maintained the brain-targeted ability of SP-sLip by selectively adsorbing apolipoproteins in blood and crossing BBB via apolipoprotein receptors. Compared to SP-sLip, DSP-sLip exhibited less aggregation in storage, enhanced stability, extended blood circulation, and reduced liver/spleen accumulation in vivo [Display omitted] • DSP-sLip exhibited less self-aggregation and enhanced stability in storage compared to SP-sLip. • DSP-sLip maintained ability to absorb apolipoproteins in blood to form functionalized protein corona. • DSP-sLip had enhanced stability, prolonged circulation, reduced liver accumulation with comparable brain-targeting efficiency as SP-sLip. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate (CS) is a linear polysaccharide chain of alternating residues of glucuronic acid (GlcA) and N -acetylgalactosamine (GalNAc), modified with sulfate groups. Based on the structure, CS chains bind to bioactive molecules specifically and regulate their functions. For example, CS whose GalNAc is sulfated at the C4 position, termed CSA, and CS whose GalNAc is sulfated at both C4 and C6 positions, termed CSE, bind to a malaria protein VAR2CSA and receptor type of protein tyrosine phosphatase sigma (RPTPσ), respectively, in a specific manner. Here, we modified CSA and CSE chains with phosphatidylethanolamine (PE) at a reducing end, attached them to liposomes containing phospholipids and generated CSA and CSE liposomes. The CS-PE was incorporated into the liposome particles efficiently. Inhibition ELISA revealed specific interaction of CSA and CSE with recombinant VAR2CSA and RPTPσ, respectively, more efficiently than CS chains alone. Furthermore, CSE liposome was specifically incorporated into RPTPσ-expressing HEK293T cells. These results indicate CS liposome as a novel and efficient drug delivery system, especially for CS-binding molecules. [ABSTRACT FROM AUTHOR]

As the aging population continues to increase, aging-related inflammation, oxidative stress, and neurodegenerative diseases have become serious global health threats. Resveratrol, a star molecule in natural polyphenols, has been widely reported to have physiological activities such as anti-aging, anti-inflammatory, antioxidant, and neuroprotection. However, its poor water solubility, rapid metabolism, low bioavailability and poor targeting ability, which limits its application. Accordingly, a brain-targeted resveratrol liposome (ANG-RES-LIP) was developed to solve these issues. Experimental results showed that ANG-RES-LIP has a uniform size distribution, good biocompatibility, and a drug encapsulation rate of over 90%. Furthermore, in vitro cell experiments showed that the modification of the targeting ligand ANG significantly increased the capability of RES to cross the BBB and neuronal uptake. Compared with free RES, ANG-RES-LIP demonstrated stronger antioxidant activity and the ability to rescue oxidatively damaged cells from apoptosis. Additionally, ANG-RES-LIP showed the ability to repair damaged neuronal mitochondrial membrane potential. In vivo experiments further demonstrated that ANG-RES-LIP improved cognitive function by reducing oxidative stress and inflammation levels in the brains of aging model mice, repairing damaged neurons and glial cells, and increasing brain-derived neurotrophic factor. In summary, this study not only provides a new method for further development and application of resveratrol but also a promising strategy for preventing and treating age-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects. Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip. BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of −22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity. BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity. [ABSTRACT FROM AUTHOR]

The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. Degradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups. [Display omitted] [ABSTRACT FROM AUTHOR]

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Lung cancer has a high incidence rate and a low cure rate, hence the urgent need for effective treatment methods. Current lung cancer drugs have several drawbacks, including low specificity, poor targeting, drug resistance, and irreversible damage to normal tissues. Therefore, there is a need to develop a safe and effective new drug that can target and kill tumor cells. In this study, we combined nanotechnology and biotechnology to develop a CD133 ligand‐modified etoposide‐liposome complex (Lipo@ETP‐CD133) for targeted therapy of lung cancer. The CD133 ligand targeted lung cancer stem cells, causing the composite material to aggregate at the tumor site, where high levels of ETP liposomes could exert a strong tumor‐killing effect. Our research results demonstrated that this nano‐drug had efficient targeting and tumor‐killing effects, indicating its potential for clinical application. [ABSTRACT FROM AUTHOR]

Contemporary nutraceutical and biomedical sectors are witnessing fast progress in efficient product development due to the advancements in nanoscience and encapsulation technology. Nutraceuticals are generally defined as food substances, or a section thereof, that provide us with health benefits such as disease prevention and therapy. Nutraceutical and biomedical compounds as well as food supplements are a natural approach for attaining therapeutic outcomes with negligible or ideally no adverse effects. Nonetheless, these materials are susceptible to deterioration due to exposure to heat, oxygen, moisture, light, and unfavorable pH values. Tocosomes, or bilayered lyotropic vesicles, are an ideal encapsulation protocol for the food and nutraceutical industries. Biocompatibility, high entrapment capacity, storage stability, improved bioavailability, site specific delivery, and sustained-release characteristics are among the advantages of this nanocarrier. Similar to liposomal carriers and nanoliposomes, tocosomes are able to encapsulate hydrophilic and hydrophobic compounds separately or simultaneously, offering synergistic bioactive delivery. This manuscript describes different aspects of tocosome in parallel to liposome and nanoliposome technologies pertaining to nutraceutical and nanonutraceutical applications. Different properties of these nanocarriers, such as their physicochemical characteristics, preparation approaches, targeting mechanisms, and their applications in the biomedical and nutraceutical industries, are also covered. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) has a considerable impact on the physical and mental health of patients. Nano preparations have apparent advantages and high feasibility in the treatment of AGA. Cardamonin (CAR) has a wide range of pharmacological activities, but it has the problems of poor solubility in water and low bioavailability. There are few, if any, researches on the use of nano-loaded CAR to improve topical skin delivery of AGA. In this study, a CAR-loaded liposomal formulation (CAR@Lip and CAR@Lip Gel) was developed and characterized. The prepared CAR@Lip exhibited a uniform and rounded vesicle in size. CAR@Lip and CAR@Lip Gel can significantly improve the cumulative release of CAR. Additionally, CAR@Lip can obviously promote the proliferation and migration of human dermal papilla cells (hDPCs). Cell uptake revealed that the uptake of CAR@Lip significantly increased compared with the free drug. Furthermore, both CAR@Lip and CAR@Lip Gel groups could markedly improve the transdermal performance of CAR, and increase the topical content of the drug in the hair follicle compared with CAR. The ratchet effect of hair follicles could improve the skin penetration depth of nanoformulations. Notably, Anti-AGA tests in the mice showed that CAR@Lip and CAR@Lip Gel groups could promote hair growth, and accelerate the transition of hair follicles to the growth stage. The anti-androgen effect was revealed by regulating the expression of IGF-1, VEGF, KGF, and TGF-β, participating in SHH/Gli and Wnt/β-catenin pathways. Importantly, the nanoformulations had no obvious skin irritation. Thus, our study showed that CAR-loaded liposomal formulation has potential application in the treatment of AGA. [ABSTRACT FROM AUTHOR]

Biofilm-associated bacterial infection brings serious threats to global public health owing to serious antibiotic resistance. It is urgently needed to develop innovative strategies to combat biofilm-associated bacterial infections. Polymyxins stand out as the last line of defense against Gram-negative bacteria. However, serious nephrotoxicity of polymyxins severely limits their clinical utility. Herein, a hypoxia-responsive liposome is designed as the nanocarrier of polymyxin B (PMB) to combat biofilms developed by Gram-negative bacteria. A metronidazole modified lipid (hypoxia-responsive lipid (HRLipid)) is synthesized to fabricate hypoxia-responsive liposomes (HRLip). PMB loaded hypoxia-responsive liposomes (HRL-PMB) is then prepared to mitigate the nephrotoxicity of PMB while preserving its excellent bactericidal activity. HRL-PMB shows very low hemolysis and cytotoxicity due to liposomal encapsulation of PMB. PMB can be readily released from HRL-PMB in response to hypoxic biofilm microenvironment, exerting its bactericidal activity to realize biofilm eradication. The excellent in vivo antibiofilm ability of HRL-PMB is confirmed by a Pseudomonas aeruginosa infected zebrafish model and a P. aeruginosa pneumonia infection model. Meanwhile, HRL-PMB can greatly reduce the nephrotoxicity of PMB after intravenous injection. The hypoxia-sensitive liposomes held great promise to improve the biosafety of highly toxic antibiotics while preserving their intrinsic bactericidal ability, which may provide an innovative strategy for combating biofilm-associated infections. [ABSTRACT FROM AUTHOR]

ObjectiveTo elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer (CRC) by using the two-sample and two-step Mendelian randomization (MR) methods, and to explore the mediating role and proportion of immune cells as intermediary factors. MethodsThe pooled statistical data related to the study were screened, and 179 lipids and CRC were analyzed using two-sample and two-step MR with the inverse variance weighted method. Simultaneously, the causal effect was verified via Bayesian weighted MR. Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits. Sensitivity, heterogeneity, and pleiotropy analyses were performed to verify the reliability of the study results. ResultsThe causal relationship between nine lipid traits and CRC was preliminarily identified, and no reverse causal effect was found (P>0.05). The validity of the results was verified via Bayesian weighted MR (P

Abstract Background The increasing trend of antibiotic resistance has posed challenges for scientists, especially in developing better drug formulations. The discovery of new antibiotics could take years. Therefore, the management of an ideal drug delivery system has become a primary focus nowadays. Main body of abstract Almost all skin diseases could be treated with the administration of topical drugs, especially infectious skin diseases. The increasing cases of antimicrobial resistance require innovative strategies and actions. In dermatokinetics, achieving optimal drug concentrations in the deepest layers of skin tissue is a significant challenge. Human skin has remarkably complex characteristics, presenting a major obstacle in efficiently maintaining drug efficacy. Nanocarriers are an important part of nanomedicine which provide excellent drug penetration through various drug delivery systems. Lipid-based nanovesicles, such as liposome, are the oldest and most potential nanovesicles for such a purpose. Several studies have shown the efficacy of liposome-contained antibiotics and offered the lowest microbial inhibition concentration (MIC). It is suggested that liposome also delivers greater drug accumulation compared to blank drugs. Short conclusion Liposome is a flexible lipid-based drug delivery that enhances drug permeation through skin tissue by mimicking the lipid bilayer system of the organ. It is non-toxic, less immunogenic, and easily degraded by enzyme. The incorporation of liposome into antibiotics may reduce the inefficient drug dosage since the encapsulation will protect the active compounds prior to being released from the vehicle. Thus, the lowest MIC and less clinical side effects will be obtained. Graphical abstract

Sepsis frequently leads to life-threatening organ failure due to an in appropriate response by the body to bacterial, viral, and fungal infections. In recent years, there has been an increasing interest in using nanoparticles to develop biomarkers and drug delivery systems that have significantly improved the treatment of infectious diseases. Herein, we update the most recent development of nanoparticle-based therapeutics for sepsis treatment. This article begins with a brief overview of how sepsis is triggered and its associated diseases. It also explores the differences between traditional and modern treatment approaches. Afterward, the reasons for embracing nanotechnology-based therapies for sepsis are summarized, including their ability to reduce inflammation, provide antioxidant effects, regulate cell signaling pathways, manage reactive oxygen and nitrogen species (RONS) production, control autophagy and apoptosis, clear lipopolysaccharides (LPS) from the blood, inhibits the formation of cell-free DNA and cytokine storms. Furthermore, the special emphasis is on updating the use of nanotechnology-mediated drug delivery systems, such as nanoparticles, liposomes, and exosomes, in the treatment of sepsis caused by various microorganisms. Moreover, we also discuss polymer mediated therapy and some dynamic therapeutic aspects in septecemia disease. In addition, the article highlights the challenges and a limitation associated with using drug delivery for sepsis treatment and expresses the hope that this review will accelerate the development of more effective sepsis therapies and facilitate the transition from research to practical clinical application.

Abstract Background Carbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited. Results In this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs. To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively. Conclusion This research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy. Graphical abstract

Nosema ceranae, a parasite that parasitizes and reproduces in the gut of honeybees, has become a serious threat to the global apiculture industry. RNA interference (RNAi) technology can be used to inhibit N. ceranae growth by targeting silencing the thioredoxin reductase (TrxR) in N. ceranae. However, suitable carriers are one of the reasons limiting the application of RNAi due to the easy degradation of dsRNA in honeybees. As a vesicle composed of a lipid bilayer, liposomes are a good carrier for nucleic acid delivery, but studies in honeybees are lacking. In this study, liposomes were used for double-stranded RNA (dsRNA) dsTrxR delivery triggering RNAi to inhibit the N. ceranae growth in honeybees. Compared to naked dsTrxR, liposome-dsTrxR reduced N. ceranae numbers in the midgut and partially restored midgut morphology without affecting bee survival and gut microbial composition. The results of this study confirmed that liposomes could effectively protect dsRNA from entering the honeybee gut and provide a reference for using RNAi technology to suppress honeybee pests and diseases.

Purpose: L-Ascorbic acid (vitamin C) is an essential water-soluble vitamin that plays an important role in various physiological functions, including immune health. The stability of vitamin C in the gastrointestinal tract its bioavailability is limited. This study aimed to investigate if a liposomal form of vitamin C can increase absorption compared to standard vitamin C. Methods: In a randomized, double-blind, placebo-controlled, crossover fashion, 19 males and 8 females (n = 27; 36.0 ± 5.1 years, 165.0 ± 6.9 cm, 70.6 ± 7.1 kg) ingested a single-dose of placebo (PLA), 500 mg vitamin C (VIT C), and 500 mg liposomal vitamin C (LV-VIT C, LipoVantage®, Specnova, LLC, Tyson Corner, VA, USA). Venous blood samples were collected 0, 0.5-, 1-, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hours after ingestion and were analyzed for plasma and leukocyte vitamin C concentration. Results: VIT C and LV-VIT C demonstrated significantly greater Cmax and AUC0 − 24 in plasma and in leukocytes compared to placebo (p < 0.001). Additionally, LV-VIT C had significantly higher Cmax (plasma + 27%, leukocytes + 20%, p < 0.001) and AUC0 − 24 (plasma + 21%, leukocytes + 8%, p < 0.001) values as compared to VIT C. Conclusion: Liposomal formulation of vitamin C increases absorption into plasma and leukocytes. Trial Registration: Clinical Trials Registry - India (CTRI/2023/04/051789). [ABSTRACT FROM AUTHOR]

Abstract Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.