Journal of Liposome Research最新文献

As an essential carrier for drug delivery systems, the stability of liposomes directly influences the efficiency and safety of drug delivery. In the complex and challenging process of in vivo delivery, the stability of liposomes is affected by both their inherent properties and external environmental factors. This paper first introduces the in vivo journey of liposomes, encompassing blood circulation, tissue distribution, metabolism, and excretion. It then summarizes the biological factors affecting liposome stability, including immune recognition, protein-lipid interactions, enzyme-catalyzed degradation, and physiological changes. Additionally, the paper explores effective strategies to enhance liposome stability, such as optimizing lipid composition and surface modification. Finally, it discusses future research directions and existing challenges, focusing on AI-assisted liposome development, and the development of biocompatible materials. The study emphasizes the critical factors affecting liposome stability, uncovers current limitations, and highlights future potential in this field, providing a theoretical foundation and practical guidance for the design and application of liposomes.

Stearyl triphenyl phosphonium (STPP) has previously been utilized to prepare mitochondriotropic liposomes for improved drug delivery to mitochondria. Additionally, liposomal STPP has shown higher toxicity toward drug-resistant tumor cells compared to non-drug-resistant tumor cells. The differential toxicity is hypothesized to be due to the differences in mitochondrial bioenergetics between drug-resistant and non-drug-resistant cells. This study aimed to further test the hypothesis by using drug-resistant and non-drug-resistant cell lines from ovarian, lung, uterine and breast carcinomas. Mitochondrial function was assessed by JC-1 dye accumulation and by measurement of oxygen consumption rate. Liposomal STPP cytotoxicity was then assessed using a metabolic assay. The drug-resistant ovarian, lung and uterine carcinoma cell lines showed higher mitochondrial activity compared to their non-drug-resistant counterparts while there was no difference in mitochondrial activity between drug-resistant and non-drug-resistant breast carcinoma cell lines. Consistent with the hypothesis of the study, liposomal STPP showed greater toxicity to the drug-resistant ovarian and uterine carcinoma cell lines compared to the non-drug-resistant cell lines and no difference in toxicity between drug-resistant and non-drug-resistant breast carcinoma cell lines. While liposomal STPP was more toxic toward the non-drug-resistant cell line in the case of lung carcinoma, the effect is likely due to the use of altered growth conditions for the non-drug-resistant cell line that were needed to allow testing by the assays used in the study. Collectively, the results suggest the potential for exploiting mitochondrial bioenergetic differences to target drug-resistant and non-drug-resistant tumor cell populations in a variety of tumor types.

The high rate of lung cancer and related deaths necessitated new treatment strategies. This study aimed at in vitro, in vivo, and ex vivo evaluation of magnetic field sensitive, ultrasound-mediated, and pemetrexed and pazopanib containing nanobubble (NB) destruction to provide dual drug therapy against non-small cell lung cancer. For this purpose, cytotoxicity analysis (CRL-5807, CRL-5826, A549-Luc-C8), biocompatibility experiments including hemocompatibility, uptake by macrophages, and binding to serum proteins, acute and long-term toxicity analyses, in vivo therapeutic efficacy experiments, pharmacokinetic analyses, histochemistry, and immunohistochemistry experiments were performed on NBs. The IC50 value of NB-400 against A549-Luc-C8 was found to be 31.4 ± 1.6 μg/mL and 34.9 ± 1.2 μg/mL with and without ultrasound application for 72 h, respectively. 30.8% of NB-400 was phagocytosed by macrophage cells and was non-hemolytic. It was determined that NB-800 (prepared for inhaler administration) and NB-400 did not cause acute or long-term toxic effects and reduced tumor size and/or disappeared after treatment, but carrier-free dual drugs did not give a therapeutic response also based on immunohistochemical analyses. It can be said that the emerging intravenous and inhaled delivery systems can be potential therapeutics that can be used in the treatment of non-small cell lung cancer with superior properties such as magnetic targeting and ultrasound sensitivity.

Breast cancer is one of the most common and deadly cancers worldwide. Melittin is the main component of bee venom, which has multiple anti-cancer properties. Targeted delivery of the gene encoding melittin using TRA-conjugated immunoliposomes to breast cancer cells can effectively treat this disease and reduce the side effects. Liposomes were prepared using the thin-film hydration method. The conjugation of TRA to liposomes was confirmed using SDS-PAGE, FTIR, and Bradford assay and characterized by DLS and TEM. The MTT, Fluorescent microscopy imaging, and flow cytometry methods were chosen to investigate the cytotoxicity and internalization of MEL/PEG-Lip and TRA/MEL immunoliposomes in the BT-474 cell line. The hydrodynamic diameter of TRA/MEL immunoliposomes was about 156 nm, and their appearance was spherical. The IC₅₀ values for TRA/MEL immunoliposomes were calculated as 7.73 and 5.41 µg/mL for 48 and 72 h, respectively, which indicated that TRA/MEL immunoliposomes had a more significant cytotoxic effect on BT-474 cells than MEL/PEG-Lip. In addition, flow cytometry results showed that TRA/MEL immunoliposomes enter BT-474 cells to a greater extent and cause apoptosis. Due to the ability of TRA/MEL immunoliposomes to target and induce apoptosis in BT-474 cancer cells, this nanostructure can be suggested as a promising alternative in the treatment of this type of breast cancer.

Demyelination leads to neuropathies and clinical deficits. Chemical remyelinating agents have variable efficacy and severe undesirable effects. Withania somnifera and Ginkgo biloba are traditionally known for possessing neuroprotective effects. The present study endeavors to reverse the demyelination using Withania somnifera root extract (WNLP) and Ginkgo biloba leaf extract (GNLP) liposomes prepared using thin-film hydration. The mean particle size (89.7 nm for WNLP, 85.5 nm for GNLP), zeta potential (-0.21 mV for WNLP, +0.455 mV for GNLP), and encapsulation efficiency (98.7% for WNLP, 97.5% for GNLP) were recorded. FTIR analysis indicated similar absorption peaks between the crude extracts and nano-liposomal formulations, with slight shifts observed. Scanning electron microscopy confirmed smooth, spherical structures. To evaluate the therapeutic efficacy of oral gavage of WNLP and GNLP in a cuprizone-induced demyelinated mice model, they were randomly divided into groups, namely Control (Healthy, Sham and Vehicle), WNLP (low and high dose), GNLP (low and high dose), Ginkgo biloba crude extract (low and high dose) and Prednisolone. Treatment efficacy was assessed using behavioral tests (SHIRPA, Rota-rod, Hot-plate, NORT, and EPM), hematobiochemical, histology, and immunohistochemical analyses. The GNLP in high doses had significant improvement compared to others, highlighting its potential as a promising therapy for demyelinating neuropathies, paving the way for advancements in neurobiomedical science.

This study explores the potential of 18-crown-6 ether to enhance liposomal integrity in biological media. A novel 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE)-crown ether conjugate was synthesized and incorporated into phosphatidylcholine/cholesterol liposomes at varying concentrations (0.5-8 mol%). The physicochemical characteristics, serum integrity, and response to divalent cations were systematically evaluated. Although, these crown ether-modified liposomes do not provide the same level of protection as PEGylation at 48 hours, they clearly exhibited improved integrity in serum at 24 hours compared to non-pegylated liposomes under the same conditions. Moreover, when exposed to calcium ions (5 mM), crown ether-modified liposomes maintained significantly greater stability levels at 24 h in comparison to unmodified liposomes. Furthermore, co-functionalization with both crown ether (2%) and PEG (2%) lipids resulted in stability identical to 4% PEGylated liposomes under the same conditions, suggesting an additive stabilization effect of crown ether and PEG, at least at the concentration applied. These findings introduce crown ether-modified liposomes as a novel approach to modulate liposome-protein interactions and potentially enhance drug delivery in physiological environments containing high concentrations of calcium.

Magnesium deficiency has been reported in association with various disease conditions, particularly in neurological diseases. The limited clinical use of magnesium sulfate is due to its restricted entry into the Central Nervous system (CNS) through blood brain barrier (BBB) which may consequently result in the peripheral accumulation followed by its toxic effects. The current study is focused on the development of nano formulation of lactoferrin conjugated liposome loaded with magnesium sulfate (LMGPLS) with an aim to improve its CNS permeability. LMGPLS was prepared by thin-film hydration technique followed by the lactoferrin conjugation. The average particle size of the LMGPLS was found to be 273.23 ± 6.7 nm. In vitro drug release studies showed that the drug release started after 15 min and continued up to 5 h from LMGPLS. The parallel artificial membrane permeability assay proved the improved lipid layer permeation of prepared formulation when compared with that of the drug solution. The prepared LMGPLS were found to be haemo-compatible and cyto-compatible when tested with blood as well as with multiple cell lines. The pharmacological effects of the formulations were evaluated by multiple in vitro experiments. The results from in vitro experiments showed that the developed formulation is capable of improving the cell viability in glutamate and H₂O₂ treated cell lines indicating its antioxidant and anti-excitotoxicity effects. Additionally, the developed liposome showed significant effect on digoxin induced Na⁺/K⁺ ATPase inhibition. Good lipid layer penetrability with haemo-compatibility and cytocompatibility warrant that the formulation will be a suitable candidate to increase the CNS delivery of Magnesium.

Concerns regarding bacterial infections and antibiotic resistance development have instigated many researchers to synthesize innovative antibacterial compounds and develop more effective pharmaceutical formulations against microorganisms increasingly adapted to our environment. In special, many efforts have been dedicated to developing pharmaceutical antibacterial formulations to treat and improve wound-healing processes, which still represent a great challenge for common clinical practice today. Liposomal systems remain one of the most extensively studied controlled delivery platforms, and considering the antibacterial context, the present article aims to provide a fast and well-oriented systematic review regarding this issue, aiming to bring to the readers the ultimate data regarding the employment of liposomes in the treatment of bacterial infections and the healing of bacteria-infected wounds. A systematic compilation of results and comparisons was made, seeking to observe the antibacterial and wound-healing behavior of the formulated liposomal systems in selected recent studies. The results obtained revealed impressive results concerning the potential applications of liposomes against bacteria in the wound-healing medical context.

5-Fluorouracil (5-Fu) is a chemotherapy drug that can treat various cancers. However, its short plasma half-life and severe adverse reactions limit its wide application in clinical utility. To overcome these drawbacks, in this study, 5-Fu long-circulating liposomes (SSL-5-Fu Lip) were prepared by the film hydration method. DSPE-PEG₂₀₀₀-FA was conjugated to the surface of SSL-5-Fu Lip through amidation reaction, resulting in the successful preparation of FA-SSL-5-Fu Lip. The particle size and zeta potential were measured. The encapsulation efficiency of 5-Fu was determined by high-performance liquid chromatography (HPLC), and the drug loading was calculated. The stability of FA-SSL-5-Fu Lip was evaluated at 4 °C based on particle size and PDI. Pharmacokinetic studies were conducted in male Sprague-Dawley (SD) rats. The average particle size of the liposomes was 139.11 ± 3.1 nm, and the zeta potential was -4.30 ± 0.91 mV. The encapsulation efficiency and drug loading of 5-Fu were 76.88 ± 4.23% and 24.14 ± 0.97%, respectively. The half-lives of 5-Fu and FA-SSL-5-Fu Lip were 0.319 h and 1.059 h, respectively. It can be preliminarily proved that FA-SSL-5-Fu Lip has the effect of prolonging circulation time. Compared with free 5-Fu, it prolongs the circulation time of the drug in the body, laying a foundation for its clinical application.

In this current work, a generic complex liposomal injectable formulation was developed. During dossier review, a regulatory agency requested to evaluate the in vivo in vitro relationship (IVIVR) and the discriminative power of dissolution media from in vivo perspective. Establishment of a bio predictive method and IVIVR for liposomes are challenging as in vivo both free and encapsulated drug are measured, while in vitro only free is measured. However, justification of the discriminative power of a dissolution method was made using physiologically based pharmacokinetic (PBPK) modeling. Physicochemical, biopharmaceutical, dissolution profiles and pivotal plasma profiles were integrated for model development. The dissolution profile fitted into first order kinetics and the in vitro K_{in vitro rel} was used to link liposomal and free drug concentrations in the blood. Model validation was proved by predicting bioequivalence (BE) ratios that are in line with the observed BE outcome. The model was applied to demonstrate discriminatory power of dissolution method by integrating K_{in vitro rel} derived from various batches. The simulated BE ratios are inline to dissolution difference and thus discriminatory power from in vivo perspective was demonstrated. This justification was accepted by agency and led to acceptance and product approval. This approach opened new avenues for describing in vivo behavior of complex intravenous liposomal formulations.