Journal of Liposome Research最新文献

Gangliosides, glycosphingolipids with one or more N-acetyl-neuraminic acid groups, play essential roles in various cellular and biological processes, among them are cell signaling, neuronal development, cell-cell recognition and the modulation of immune response. Based on their multiple biological roles, the pharmacological utilization of gangliosides for the therapy of several clinical conditions is currently widely being explored but hampered by its limited water solubility. To increase the bioavailability of poorly water-soluble therapeutic agents, pharmaceutical nanocarriers such as liposomes have been developed over the last fifty years. Ganglioside GM1 incorporated into liposomes was proposed during the 1980s for rendering them long-circulating following their intravenous administration, but GM1 was soon replaced by polyethylene glycol which gave rise to the concept of Stealth Liposomes. More recently, the ability of exogenous GM1 to ameliorate oxidative stress was revealed, leading us to investigate the cytoprotective effect of liposomal GM1 under a variety of pathological conditions. Here we review all data showing the antioxidant effect of exogeneous GM1 and based on literature findings and our own, we propose a mechanism by which liposomal exogenous GM1 is able to trigger the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which is a critical cellular defense mechanism protecting against oxidative stress and other types of cellular damage.

This study aimed to design a novel liposome containing GA modified phosphatidylcholine lipid (GA-PC Lip) and determine its susceptibility to tumor over-expressed secretory phospholipase A₂ (sPLA₂) and its anti-cancer effect compared to conventional liposomes (Convention Lip). The liposomes were characterized for size, drug loading, encapsulation efficiency, and stability. A 6-CF release assay was conducted to assess the sensitivity of the liposomes to the tumor-overexpressed secretory phospholipase A₂ (sPLA₂). In vitro experiment, the sPLA₂ levels in the Colo205 cell culture medium were detected by the Elisa kit and the anti-cancer effect of the oxaliplatin (L-OHP) loaded GA-PA Lip was analyzed by the CCK-8 assay. Results showed that both of L-OHP loaded formulations (GA-PC Lip and Convention Lip) had similar particle sizes of ∼100 nm and close entrapment efficiency values of 4.5-4.8%. The results of CF release assay indicated that the labeled GA-PC Lip had released more quickly than CF labeled Convention Lip in the presence of Bv sPLA₂ and GA-PC Lip had a release of about 95% 6-CF at 2 h, whereas Convention Lip only released about 13% 6-CF. In addition, the average concentrations of sPLA₂ in the cell-conditioned medium (CCM) of Colo205 cancer cells increased with incubation time and L-OHP loaded GA-PC Lip had much greater anti-proliferative activity than Convention Lip against Colo205 cells. These findings suggest that GA-PC Lip is an ideal complex for sPLA2-triggered release and has potential applications in enzyme-triggered smart anti-cancer drug release system to increase the anti-cancer effect.

Micro-145 down-regulation is frequently found in breast cancers, indicating its potential as a therapeutic target. The introduction of exogenous miR-145 directly to the tumor sites has been a hurdle due to limited delivery, low bioavailability, and hence lower therapeutic efficacy. Thus, this study aims to synthesize and characterize PEGylated liposome co-loaded with Dox-HCl and miR-145 mimics to investigate its in-vitro anti-proliferative activity against MDA-MB-231 cells. The formulations were developed using a composite central design to optimize nanoparticle size and encapsulation efficiency (EE%) of Dox-HCl and miR-145 mimics. The optimized formulation exhibited the highest desirability function (D = 0.814) and displayed excellent stability over 60 days at 4 °C, maintaining a stable nanoparticle size and zeta potential, with relative EE% of Dox-HCl and miR-145 mimics on the final incubation day 94.97 ± 0.53% and 51.96 ± 2.67%, respectively. The system displayed a higher rate of drug release within 4 h of incubation at an acidic condition. Additionally, the optimized formulation demonstrated a higher toxicity (IC₅₀ = 0.58 μM) against MDA-MB-231 cells than the free Dox- HCl and miR-145 regimen (IC₅₀ = 1.00 μM). Our findings suggest that PEGylated liposome is tunable for effective concurrent delivery of anticancer drugs and therapeutic miRNAs into tumor cells, necessitating further investigation.

Taxane drugs are clinically used for the treatment of many types of cancers due to their excellent antitumor effects. However, the surfactants contained in the injections currently used in the clinic may have serious toxic side effects on the organism, making it necessary to develop new dosage forms. Cationic liposomes have been widely used in antitumor research because of their advantage of preferentially targeting tumor neovascularization, but antitumor by targeting tumor vasculature alone does not necessarily provide good results. Malignant tumors represent complex ecosystems, tumor-associated macrophages (TAMs) and tumor endothelial cells (TECs) in the tumor microenvironment play crucial roles in tumor growth. Therefore, given the ability to achieve active targeting of TAMs and TECs by using sialic acid (SA) as a targeting material, the potential of cationic nanoformulations to preferentially target neovascularization at the tumor site, and the excellent antitumor effects of the taxane drugs docetaxel (DOC), in the present study, sialic acid-cholesterol coupling (SA-CH) was selected as a targeting material to prepare a DOC cationic liposome (DOC-SAL) for tumor therapy. The results of the study showed that DOC-SAL had the strongest drug accumulation in tumor tissues compared with the common DOC formulations, and was able to effectively reduce the colonization of TAMs, inhibit the proliferation of tumor cells, and have the best tumor-suppressing effect. In addition, DOC-SAL was able to improve the internal microenvironment of tumors by modulating cytokines. In summary, this drug delivery system has good anti-tumor effects and provides a new option for tumor therapy.

The high complexity of biological membranes has driven the development and application of a wide range of model membrane systems. Among these models, liposomes are extensively used because of their versatility in mimicking cellular membranes with a wide range of lipid compositions. However, the accurate quantification of lipid components, such as sterols, within these models remains a critical requirement for validation, data interpretation, and comparison. Here, we present a reliable and sensitive colorimetric assay using the Zak color reaction, which we have specifically adapted for the quantification of sterols at the micro-scale level. The assay was evaluated using cholesterol, ergosterol, and sitosterol standards, reflecting the diversity of sterol species across organisms. The reaction mechanism involves the dehydration of sterols to form carbonium ions, which are oxidized to form various enylic carbonium ions with specific absorption peaks. Due to the different chemical structures of cholesterol, ergosterol, and sitosterol, the resulting spectra show that the colored reaction products are formed in different proportions. The stability and interconversion of these species over time were analyzed. Cholesterol and sitosterol showed a clear peak at 555 nm, while ergosterol had prominent peaks at shorter wavelengths. Sterol assays on liposomal preparations showed accurate sterol incorporation with minimal loss during processing steps. These results demonstrate that this assay provides a robust and accurate measurement of sterol content in large unilamellar vesicles, making it a valuable tool for liposomal studies.

Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.

This study aimed to formulate diacerein loaded terpene-enriched invasomes (DCN-TINV) to fulfill a fruitful management of osteoarthritis. A 2³ factorial design was adopted, including A: cholesterol concentration (%w/v), B: ethanol volume (mL) and C: phosphatidylcholine: drug ratio as the studied factors. Invasomes were constructed using the thin film hydration technique. Herein, percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI) and zeta potential (ZP) were statistically analyzed using Design-Expert^® software to select the optimum formula. The selected criteria for detecting the optimum formula were restricting PS (<350 nm), dismissing PDI, magnifying ZP (as absolute value) and EE%. The selected formula was further scrutinized through multiple in-vitro studies, including Fourier-transform infrared spectroscopy, differential scanning calorimetry, pH measurement, stability study, release profile and transmission electron microscopy. Furthermore, the ex-vivo performance was evaluated through ex-vivo skin permeation and deposition. Finally, it was subjected to an array of in-vivo tests, namely Draize test, histopathology, In-vivo skin penetration, edema size, and nociception inhibition measurements. The optimum formula with desirability (0.913) demonstrated EE% (89.21% ± 2.12%), PS (319.75 ± 10.11 nm), ZP (-55 ± 3.96 mV) and a prolonged release profile. Intriguingly, revamped skin permeation (1143 ± 32.11 µg/cm²), nociception inhibition (77%) and In-vivo skin penetration (144 µm) compared to DCN suspension (285 ± 21.25 µg/cm², 26% and 48 µm, respectively) were displayed. The optimum DCN-TINV exhibited plausible safety and stability profiles consolidated with auspicious efficacy for better management of osteoarthritis.

To enhance cytoplasmic delivery efficiency, pH-sensitive liposomes (PSL) have been proposed as a novel strategy. To facilitate clinical translation, this study aims to understand the impact of both size and pH-sensitivity on cellular uptake pathways, intracellular trafficking and pharmacokinetics of liposomes. The large liposomes (130-160 nm) were prepared using thin-film hydration method, while small liposomes (∼60 nm) were fabricated using microfluidics, for both PSL and non-pH-sensitive liposomes (NPSL). Cellular uptake pathways and intracellular trafficking was investigated through confocal imaging with aid of various endocytosis inhibitors. Intracellular gemcitabine delivery by various liposomal formulations was quantified using HPLC, and the cytotoxicity was assessed via cell viability assays. Pharmacokinetics of gemcitabine loaded in various liposomes was evaluated in rats following intravenous administration. Larger liposomes had a higher loading capacity for hydrophilic gemcitabine (7% vs 4%). Small PSL exhibited superior cellular uptake compared to large PSL or NPSLs. Moreover, the alkalization of endosomes significantly attenuated the cellular uptake of PSL. Large liposomes (PSL and NPSL) predominantly entered cells via clathrin-dependent pathway, whereas small liposomes partially utilized caveolae-dependent pathway. However, the long circulation of the liposomes, as measured by the encapsulated gemcitabine, was compromised by both pH-sensitivity and size reduction (9.5 h vs 5.3 h). Despite this drawback, our results indicate that small PSL holds promise as vectors for the next generation of liposomal nanomedicine, owing to their superior cytoplasmic delivery efficiency.

In this study, it was aimed to analyze the effects of liposomes on the dyeing of polyacrylonitrile fabrics. For this purpose, firstly liposome synthesis was carried out, and then liposome production was confirmed by Fourier transform infrared spectroscopy analysis. Additionally, zeta potential measurements were carried out to see whether stable structures were formed. Then, a selected basic dye was encapsulated with a liposome and the possibilities of using these capsules as alternative to retarders in the dyeing of polyacrylonitrile fabrics were examined. According to results obtained, it can be said that the 1% solution of synthesized liposomes creates a more stable suspension with a polydispersity index of 0.472 and the average particle size of 165.2 nm. On the other hand, it has been revealed that if 1% liposome is used in dyeing, a kind of retarder effect can be achieved in the dyeing of polyacrylonitrile fabrics. Moreover, it can be said that the decrease in color efficiency, that is, the loss of yield, caused by the use of liposome at the end of dyeing is lower compared to the retarder. This is also a very important issue, because a good retarder is expected to slow down the dye uptake, but not reduce the dye intake too much at the end of the dyeing. Dyeing levelness (%) was found to be 96.1, 97.4, and 97.1 for dyeings without auxiliary, with 1% cationic retarder and with 1% liposome, respectively. Beyond this, no significant difference was observed in terms of fastness of dyeing.

Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improving hypoxic tumor conditions, and causing reduction in the synthesis of biomolecules, which are vital for cancer growth. However, as an orally administered drug, Met has low bioavailability and rapid renal clearance. Thus, the goal of this study was to vectorize Met inside liposomes in the context of triple negative breast cancer (TNBC), which currently lacks treatment options when compared to other types of breast cancer. Vectorization of Met inside liposomes was done using Bangham method by implementing double design of experiment methodology to increase Met drug loading (minimum-run resolution V characterization design and Box-Behnken design), as it is generally extremely low for hydrophilic molecules. Optimization of Met-loaded liposome synthesis was successfully achieved with drug loading of 190 mg/g (19% w/w). The optimal Met-liposomes were 170 nm in diameter with low PdI (< 0.1) and negative surface charge (-20 mV), exhibiting sustained Met release at pH 7.4. The liposomal Met delivery system was stable over several months, and successfully reduced TNBC cell proliferation due to the encapsulated drug. This study is one the first reports addressing liposome formulation through thin-film hydration using two design of experiment methods aiming to increase drug loading of Met.