Journal of Liposome Research最新文献

The development of an inhalation powder (IP) for cancer therapy is desired to improve the therapeutic response and patient compliance. The latest studies highlighted that statins, a class of drugs used in hypercholesterolemia, can have anticancer and antiinflammatory properties. Therefore, the aim of the study was to develop an IP containing liposomes loaded with simvastatin using spray drying technology, as well as to investigate the influence of formulation factors on the quality attributes of the IP by means of experimental design. Results highlighted that the composition of liposomes, namely type of phospholipid and cholesterol concentration, highly influences the quality attributes of IP, and the use of optimal concentrations of excipients, i.e. D-mannitol and L-leucine, is essential to preserve the characteristics of liposomes throughout the spray drying process. The in vitro characterization of the optimal IP formulation revealed that the total percentage of released drug is higher from the IP formulation compared to the powder of active substance (53.38 vs. 42.76%) over a period of six hours, and 39.67% of dry particles have a size less than 5 µm, making them suitable for inhalation. As a conclusion, spray drying technology can be effectively used in the development and preparation of IP containing liposomes.

In different types of cancer treatments, cancer-specific T cells are required for effective anticancer immunity, which has a central role in cancer immunotherapy. However, due to the multiple inhibitions of CD8⁺ T cells by tumor-related immune cells, CD8⁺ T-cell mediated antitumor immunotherapy has not achieved breakthrough progress in the treatment of solid tumors. Receptors for sialic acid (SA) are highly expressed in tumor-associated immune cells, so SA-modified nanoparticles are a drug delivery nanoplatform using tumor-associated immune cells as vehicles. To relieve the multiple inhibitions of CD8⁺ T cells by tumor-associated immune cells, we prepared SA-modified doxorubicin liposomes (SL-DOX, Scheme 1A). In our study, free SA decreased the toxicity of SL-DOX to tumor-associated immune cells. Compared with common liposomes, SL-DOX could inhibit tumor growth more effectively. It is worth noting that SL-DOX could not only kill tumor-related neutrophils and monocytes to relieve the multiple inhibitions of CD8⁺ T cells but also induce immunogenic death of tumor cells to promote the infiltration and differentiation of CD8⁺ T cells (Scheme 1B). Therefore, SL-DOX has potential value for the clinical therapeutic effect of CD8⁺ T cells mediating anti-tumor immunotherapy.

'Active targeting' refers to modifying a nanocarrier's surface with targeting ligands. This study introduced an efficient approach for immobilizing imidazole-based drugs onto the metallated-porphyrin complex within the porphysome nanocarrier. To enhance cellular and bacterial uptake, a Ni-porphyrin with a fatty acid tail was synthesized and placed in the bilayer center of DPPC, facilitating receptor-mediated endocytosis. The Ni-porphyrin in the head group of the Ni-porphyrin-tail was placed superficially in the polar region of the membrane. Spherical unilamellar vesicle formation (DPPC: Ni-porphyrin-tail 4:1 mole ratio), as metallo-porphysome, was achieved through supramolecular self-assembly in an aqueous buffer. These vesicles exhibited a diameter of 279 ± 7 nm and a zeta potential of -15.3 ± 2.5 mV, showcasing their unique cytocompatibility. Nitroimidazole was decorated on the surface of metallo-porphysomes and pistachio green hull extract (PGHE) was loaded into the carrier for synergistic activity against (E. coli) and (S. aureus) bacteria strains. The physicochemical properties of Nitroimidazole-porphysome-PGHE, including size, zeta potential, morphology, loading efficiency, and release profile under various pH and temperature conditions in simulated gastrointestinal fluids were characterized. This combination therapy prevented bacterial cell attachment and biofilm formation in Caco-2 cells, as colon epithelial cells. The remarkable benefit of this system is that it does not affect cell viability even at 0.5 mg/ml. This study demonstrates the potential of a new co-delivery system using biocompatible metallo-porphysomes to decrease bacterial infections.

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.

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.

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.

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.

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.

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.