Journal of Liposome Research最新文献

Liposomes with unique internal states and morphology have profound implications for controlled drug delivery. This article demonstrates that the final morphology (oblong vs. spherical) and internal state of irinotecan as irinotecan-SucroseOctaSulfate(SOS) complex (gelled vs. precipitated) are impacted by the physical state (solid powder vs. liquid solution) of the used drug-entrapping agent, TEA-8-SOS (Triethylamine-octa-sucroseoctasulfate), which additionally defines the corresponding in-vitro drug release profile (sustained vs. rapid release). TEA-8-SOS is available as a semicrystalline, highly hygroscopic powder from Toronto Research Chemical (TRC). Nanoliposomes prepared from these semi-crystalline TEA-8-SOS have mostly gelled internal structure and based on the drug loading concentration or stability ratio (SR), produce either spherical or oblong morphology with implications on sustained in vitro irinotecan release profile. Alternatively, Na-SOS synthesized from sucrose, can be desalted using ion-exchange resins into the free acid form of SOS. However, when Sucroseoctasulfate (free acid form; that does not crystallize), when adjusted to desired pH with TEA (4.2 or 5.5), was used as a drug entrapping agent in the liquid form, the resultant nanoliposome has a precipitated internal structure of irinotecan-SOS complex as revealed in the high-resolution Cryo-TEM images Additionally, the lack of long-range interactions in their internal structure causes irinotecan to be rapidly released from these liposomes. Further, these liposomes have a spherical morphology as opposed to the oblong or prolate morphology seen in irinotecan liposomes prepared with semi-crystalline TEA-8-SOS (similar to Onivyde^®). SAXS power-law analysis also confirms low fractal dimension internal structures in liposomes prepared with liquid TEA-8-SOS compared to TRC's semi-crystalline, powder TEA-8-SOS.

Rising ecological concerns are driving industries, including leather manufacturing, to adopt more sustainable practices. A major focus is transitioning from traditional chemical-based methods to bio-based alternatives. Enzyme-based unhairing has emerged as a potential replacement for the conventional lime-sulfide process. However, it faces challenges such as poor enzyme stability under harsh processing conditions, high cost, and possible grain damage resulting from uncontrolled enzymatic activity. Herein, we propose using egg-derived L-α-phosphatidylcholine (EPC) liposomes as protective carriers to encapsulate protease, aiming to improve its stability and efficacy during the unhairing process. Protease-loaded EPC liposomes (EPC+Pro) were synthesized and characterized for their size, zeta potential, thermal behavior, and morphology. The average size of EPC+Pro liposomes was 386 ± 10 nm with a zeta potential of -46 ± 0.1 mV. When applied to goat skin, EPC+Pro liposomes enabled complete (100%) hair removal within 3 h, while the unhairing process using free protease required 5 h to achieve comparable results. Beyond ensuring quick and efficient hair removal, EPC+Pro demonstrated a dual function by acting as a natural fatliquor, markedly enhancing the softness of leather with low fatliquor consumption. The treated leather showed a softness of 5.13 ± 0.2 mm, higher than the 4.26 ± 0.3 mm observed with free protease treatment. Overall, EPC+Pro treated leather demonstrated superior physical properties. This study highlights the potential of protease-encapsulated liposomes as a dual-functional, efficient, and sustainable solution for enzymatic unhairing, offering improved process efficiency, enhanced leather quality, and reduced chemical usage for commercial leather processing.

Microfluidic arrays have been successfully implemented for the design and development of liposome nanoparticles. In this study we have applied a Quality by Design (QbD) approach to investigate the effect of 3D printed Tesla microfluidic designs (direct and serpentine shape) on the liposome nanoparticles in comparison with conventional ultrasonication methodology. Critical processing parameters (CPP) such as the shape, length and channel width of the Tesla arrays were also studied. Furthermore, the effect of critical material attributes (CMA), including the length of the phosphatidylcholine (PC) carbon chain and the lipid:cholesterol ratio on the produced nanoparticles was investigated. The obtained findings revealed that both CPP and CMA play a key role in the formation of liposome nanoparticles. The liposome size was decreasing with a descending order for plain array > Tesla _(serpentine) > Tesla _(direct) > ultrasonication. However, improved Tesla arrays with narrow channel width (200 μm) produced the smallest liposome particle size (74 nm). The PC carbon chain length was critical for the obtained particle size where Lipoid S75 produced smaller nanoparticles when compared to Lipoid E80. The increase of cholesterol content resulted in liposome size reduction and decreased zeta-potential.

Moringa A (MA), the hepatoprotective components of Moringa oleifera Lam. seeds, are metabolized and eliminated quickly in the body. In this study, cholesterol-modified chitosan (CH-CS) was used as a polymer carrier to prepare chitosan-modified MA liposomes (MA-CLs) in order to slow down the release of MA, prolong its circulation time, and improve the oral bioavailability of MA in comparison with common MA liposomes (MA-Ls). The particle size (PS) of MA-CLs was 218.25 ± 1.07 nm, with a polydispersity index (PDI) of 0.143 ± 0.005 and a zeta potential (ZP) of 30.64 ± 0.29 mV. The encapsulation efficiency (EE) was 85.17 ± 1.70%, while the drug loading (DL) was 7.92 ± 0.16%. In contrast, the PS of MA-Ls was 232.06 ± 1.36 nm, with a PDI of 0.215 ± 0.009 and a ZP of -14.21 ± 0.33 mV. The EE and DL of MA-Ls were 71.34 ± 0.60% and 8.39 ± 0.07%, respectively. These results indicated that MA liposomes could effectively mitigate the burst release of MA, thereby enhancing its oral bioavailability. Furthermore, the performance of MA-CLs was superior to that of MA-Ls. ELISA kits demonstrated that, both MA and MA liposomes groups significantly reduced the levels of ach detection index in mice. Specifically, the therapeutic effect followed the order: MA-CLs > MA-Ls > MA, thus exhibiting a concentration-dependent manner. Histopathological analysis of liver sections revealed that MA and its formulations alleviated hepatocyte swelling and necrosis, thereby protecting the liver from alcohol-induced damage. This study found that MA has a protective effect on the liver, while MA-CLs hold promise as a therapeutic agent for prevention of acute alcoholic liver injury (ALI).

This study addresses the limitations of traditional cancer therapies-such as high toxicity and non-selectivity-by developing a novel nanoparticulate system co-loaded with plant-derived compounds, apigenin (APG) and oleanolic acid (OA). These naturally occurring phytochemicals are known for their anticancer properties but face clinical challenges due to poor solubility and limited efficacy. The Apigenin and Oleanolic Acid Nanoparticulate System (AONS) was refined and optimized using the Box-Behnken statistical design approach, resulting in nanoparticles with a mean diameter of 169 nm and size homogeneity. A validated HPLC technique was employed to simultaneously quantify both apigenin and oleanolic acid in the developed formulation as well as in various biological matrices. In vitro drug release was enhanced at acidic pH (5.5), mimicking the tumor microenvironment. AONS showed strong physicochemical stability under refrigerated storage. Cytotoxicity tests on HepG2, MDA-MB-231, and U87 glioma cells demonstrated significantly improved anticancer activity compared to control, free drugs, or individual nanoformulations. Cellular uptake studies confirmed efficient internalization in U87 cells, and ELISA results indicated apoptosis via activation of the p53 pathway. Biodistribution analysis revealed prolonged systemic drug retention with AONS (up to 72 hours), surpassing the short circulation time of free drugs. Notably, LC-MS data confirmed that the nanoparticle system could cross the blood-brain barrier, highlighting its therapeutic potential for treating brain cancers.

Alzheimer's disease treatment faces challenges with conventional oral formulations of donepezil (DNP). This study aims to develop and characterize DNP-loaded Lactoferrin (LCF)-linked PEG-coated nano-carriers for intranasal delivery. The formulation was developed using a Quality by Design (QbD) approach integrated with molecular docking. A novel micelle-enhanced spectrofluorimetric method was developed and validated for in-vitro and in-vivo characterization of the nano-carriers. The method was optimized using Analytical Quality by Design (AQbD) principles. In-vivo pharmacokinetic and bio-distribution studies were conducted in rats to compare the developed formulation with uncoated NLCs and conventional dosage forms. The LCF-PEG-coated NLCs showed improved brain targeting efficiency compared to uncoated NLCs and conventional formulations. The spectrofluorimetric method demonstrated high sensitivity and reliability for both in-vitro and in-vivo analyses. The developed DNP-loaded LCF-PEG-coated NLCs show promise as an effective intranasal delivery system for Alzheimer's disease treatment. The novel spectrofluorimetric method offers a sustainable and efficient alternative to conventional LC-MS/MS techniques for characterizing DNP formulations.

Phytosterols, like stigmasterol, have been studied for their antioxidant, immunomodulatory, and anticancer properties. However, their lipophilic nature and biological instability make it challenging to incorporate them in food supplements and medicinal products. Liposomes offer many benefits in sterols' entrapment and delivery them due to their high bioavailability, low toxicity, and ability to target specific tissues. The purpose of this study was to develop stigmasterol-loaded liposomes using HSPC (Hydrogenated Soy Phosphatidylcholine) and HSPC:DMPC (Dimyristoylphosphatidylcholine). The impact of increasing stigmasterol concentrations on the physicochemical stability of the liposomal formulations was analyzed by dynamic light scattering. The results showed that HSPC-based liposomes could incorporate higher amounts of stigmasterol compared to the HSPC:DMPC-based liposomes. Further analysis through differential scanning calorimetry revealed the formation of metastable phases in HSPC:DMPC:stigmasterol lipid bilayers. Finally, an in vitro MTS assay on HEK-293 cells demonstrated the low toxicity of the stigmasterol-loaded nanoplatforms. In conclusion, stigmasterol, not only contributed to the stability of liposomal formulation but exhibited low cell toxicity on HEK-293 line and could be used as a valuable compound in liposomal drug delivery formulation.

Tumor cells cultured as spheroids have been shown to be superior to tumor cells cultured in monolayers as in vitro models of solid tumors because they exhibit features of the tumor microenvironment (TME) such as cell-cell interactions, extracellular matrix and diffusional gradients. However, spheroids composed solely of tumor cells, i.e. monoculture spheroids, still lack the non-tumor cell components that contribute to additional in vivo TME complexity. This study, explored the development of triple co-culture spheroid models incorporating tumor cells, tissue specific fibroblasts, and endothelial cells to mimic more of the features of the in vivo TME. Using a modified liquid overlay technique, triple co-culture spheroids were successfully generated for both drug resistant lung tumor cells as well as drug resistant ovarian tumor cells. The triple co-culture models exhibited several characteristics of in vivo tumors, including extracellular matrix (ECM) production and distinct spatial locations of cell types. Notably, fibroblasts remained in the core as the spheroid grew, while endothelial cells were found in the core only in the presence of fibroblasts. A liposomal formulation previously shown in monolayer cultures to have selective toxicity toward multiple drug resistant tumor cell types was significantly less toxic and showed composition-dependent levels of toxicity in spheroid cultures with multiple cell types. These findings demonstrate that triple co-culture spheroids can serve as in vitro models that more closely mimic in vivo tumor characteristics to facilitate the optimization of antitumor therapies prior to in vivo testing.

This study optimized the preparation conditions of sulfated glucan from Saccharomyces cerevisiae liposomes (SGSCL) and evaluated its effect on immune activity. SGSCL was prepared using the reverse evaporation method, and its immune activity was assessed by measuring the proliferation of chicken spleen lymphocytes, hemagglutination inhibition (HI) antibody titers, and serum cytokine concentrations in chickens vaccinated with the Newcastle disease (ND) vaccine. The optimal preparation conditions were a phospholipid-to-cholesterol mass ratio of 5.4:1, a phospholipid-to-SGSC mass ratio of 10:1, and a rotary evaporation temperature of 40 °C. The average encapsulation efficiency (EE) was 63.92%, whereas the mean particle size, polymer dispersity index (PDI), and zeta potential were 90.39 ± 1.71 nm, 0.203 ± 0.004, and -41.13 ± 1.05 mV, respectively. SGSCL significantly promoted the proliferation of chicken spleen lymphocytes, splenic T and B lymphocytes at concentrations of 100-800 µg/mL, 800 µg/mL and 200-800 µg/mL in vitro. The best proliferative effect on splenic lymphocytes were at 400 µg/mL, 800 µg/mL, and 800 µg/mL. In vivo, on days 7 and 14, HI antibody titers in the SGSCL-H, SGSCL-M, and SGSCL-L groups were significantly greater than those in the VC group. The serum antibody titers in the SGSCL-H and SGSCL-M groups were significantly or numerically elevated compared to the VC group at all time points post-vaccination. The IL-2, IL-6, IL-4, and IFN-γ concentrations in the SGSCL-H group were significantly higher than that in the VC group on D28 and D35. These findings suggest that SGSCL could serve as a novel vaccine diluent or immune adjuvant.