Journal of Liposome Research最新文献

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.

In this study, liposomes consisting of soybean phosphatidyl choline (SoyPC) and different molar concentrations (10 mol% and 20 mol%) of dioleoyl trimethylammoniumpropane (DOTAP) were prepared by the thin film hydration method and coated with sodium hyaluronate (NaHA) of different MWs (8-15 kDa, 30-50 kDa and 90-130 kDa) and concentrations (0.01-0.2% w/w) using phosphate buffer (PB) or glycerol phosphate buffer (G-PB) as the hydration medium. These NaHA coated liposomes could have a potential in the treatment of dry mouth since glycerol and NaHA are known for their lubricating and hydrating properties. The liposomes composed of SoyPC-DOTAP 20 mol%, and coated with NaHA MW 90-130 kDa, 0.05% w/w were found to be most stable during storage. The liposomes with 20 mol% DOTAP coated with NaHA MW 30-50 kDa, 0.05% w/w showed promising results as these stayed stable for at least two weeks. However, the liposomes coated with NaHA MW 8-15 kDa were generally unstable irrespective of the combinations of the investigated parameters. When the stable liposomes were introduced into artificial saliva (AS), aggregation rapidly occurred. Sodium alginate (NaAlg) coated liposomes that were prepared for comparison were found to be stable in AS. The study has demonstrated the influence of the amount of charged lipid which must be high, the polymer MW which must lay in the area 30 kDa-130 kDa and coating concentration which should be intermediate 0.05% w/w in preparing stable NaHA coated liposomes. Further studies need to be conducted to understand the instability exhibited by the NaHA coated liposomes in AS.

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.

Background: Lactoferrin (Lf), a multifunctional glycoprotein known for its roles in immune modulation, iron metabolism, and antimicrobial activity, has limited therapeutic efficacy due to poor bioavailability. Liposomal encapsulation of lactoferrin (LLf) offers a potential solution by improving its stability, absorption, and sustained release, making it a promising candidate for various clinical applications. This study aims to compare the effectiveness of LLf and plain Lf in cellular uptake, proliferation, and wound healing using HEK-293T and Caco-2 cell lines.

Methods: Cell uptake, proliferation, and wound healing assays were conducted using HEK-293T and Caco-2 cells to evaluate the bioavailability and therapeutic efficacy of LLf compared to plain Lf. The cellular uptake was assessed over a 24-h period using an indirect ELISA method. Cell proliferation was measured using the MTT assay, while wound healing was evaluated using a scratch assay to observe cell migration over 48 h.

Results: LLf demonstrated significantly higher cellular uptake in both HEK-293T and Caco-2 cells, with peak internalization at 4 h, compared to plain Lf. In proliferation studies, LLf showed a dose-dependent increase in cell growth, achieving a 71% proliferation rate at 75 µg/mL, while plain Lf reached only 53%. LLf also accelerated wound healing, with nearly complete closure by 48 h, compared to 51.3% closure with plain Lf.

Conclusion: The results indicate that liposomal encapsulation significantly enhances lactoferrin's bioavailability, proliferation-inducing capacity, and wound healing efficacy. LLf's superior performance in these key areas suggests its potential for broader therapeutic applications, particularly in wound care, immune modulation, and tissue regeneration. Future clinical studies are warranted to validate the therapeutic benefits of LLf in vivo.

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.

Infantile hemangiomas (IH) are common benign soft tissue tumors, frequently affecting infants. While Propranolol Hydrochloride (Pro HCl) has emerged as a promising treatment for IH, its topical application remains challenging due to the need for stable and efficacious carriers. This study investigates the potential of preformulated liposomes as carriers for topical delivery of Pro HCl for the treatment of IH in compounding pharmacies. Liposomes loaded with Pro HCl were prepared using active pharmaceutical ingredient or commercially available propranolol tablets and various dilution media, including Water for Injection (WFI), Dextrose 5%, and NaCl 0.9%. The physicochemical properties of the liposomal formulations (Pro HCl content, encapsulation efficiency, loading capacity, and colloidal stability) were assessed over a 90-day storage at 4 °C. In vitro release kinetics and transdermal permeation of Pro HCl from liposomes were also evaluated. Liposome properties were influenced by the dilution medium. Pro HCl content remained stable in liposomes encapsulating API (Lipo-Pro), regardless of the dilution medium. Lipo-Pro showed sustained drug release over time, suggesting its potential for maintaining therapeutic levels. Pro HCl exhibited enhanced transdermal permeability from Lipo-Pro compared to aqueous solution, indicating its potential for topical IH treatment. Preformulated liposomes offer a stable and effective carrier for Pro HCl, potentially suitable for extemporaneous preparations in compounding pharmacies. Their enhanced transdermal permeability presents a promising alternative for topical IH treatment. This study provides valuable insights into the development of innovative and effective drug delivery strategies for managing IH, with future research focusing on in vivo applications and therapeutic potential.

Transdermal drug delivery systems (TDDS) have received significant attention in recent years. TDDS are flexible systems that transport active components to the skin for either localized or systemic delivery of drugs through the skin. Among the three main layers of skin, the outermost layer, called the stratum corneum (SC), prevents the entry of water-loving bacteria and drugs with a high molecular weight. The challenge lies in successfully delivering drugs through the skin, which crosses the stratum corneum. The popularity of lipid-based vesicular delivery systems has increased in recent years due to their ability to deliver both hydrophilic and hydrophobic drugs. Ethosomes are specialized vesicles made of phospholipids that can store large amounts of ethanol. Ethosome structure and substance promote skin permeability and bioavailability. This article covers ethosome compositions, types, medication delivery techniques, stability, and safety. In addition to this, an in-depth analysis of the employment of ethosomes in drug delivery applications for a wide range of diseases has also been discussed. This review article highlights different aspects of ethosomes, such as their synthesis, characterization, marketed formulation, recent advancements in TDDS, and applications.

Neogambogic acid (NGA), which possesses a variety of anticancer activities, is visualized as an anticancer bioactive ingredient. However, the huge vascular stimulation, poor aqueous solubility, and short half-life restricted its clinical use. In this work, an effective nanocarrier was explored to reduce toxicity and enhance the tumor-targeted delivery. Two liposomal formulations, neogambogic acid liposomes (NGA-L), and hyaluronic acid-coated neogambogic acid liposomes (HA-NGA-L) were prepared and characterized with high encapsulation efficiency, slow pattern of drug release, narrow size distribution and higher stability. The cytotoxicity and cellular uptake of HA-NGA-L were higher than those of NGA-L in MDA-MB-231 cells (high CD44 expression), while no obvious differences in MCF-7 cells with (low CD44 expression), suggesting the CD44-mediated cellular internalization of hyaluronic acid-modified liposomes enhanced the cytotoxicity. Mechanistically, elevation of Bax and caspase-3 as well as downregulation of Bcl-2 led to cell apoptosis. Besides, the vascular stimulation and the hemolysis test indicated good safety of HA-NGA-L. In addition, HA-NGA-L was the effective nanocarrier to repress tumor proliferation in MDA-MB-231 tumor xenograft mouse through CD44 mediated active targeting without any obvious histopathological abnormities on major organs. Immunohistochemistry analysis revealed the enhanced elevation of Bax and caspase-3, and reduced expression of Bcl-2 contribute to apoptosis in tumors. Meanwhile, HA-NGA-L increased the AUC and t_1/2 by 5.34-fold and 3.94-fold, respectively. In summary, the present study shows that HA-NGA-L may be safe and effective for the tumor-targeted delivery of neogambogic acid.

Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and in vitro and ex vivo drug release. An in vivo study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. The in vitro and ex vivo drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.

Liver disorders present a significant global health challenge, necessitating the exploration of innovative treatment modalities. Liposomal nanocarriers have emerged as promising candidates for targeted drug delivery to the liver. This review offers a comprehensive examination of the mechanisms and applications of liposomal nanocarriers in addressing various liver disorders. Firstly discussing the liver disorders and the conventional treatment approaches, the review delves into the liposomal structure and composition. Moreover, it tackles the different mechanisms of liposomal targeting including both passive and active strategies. After that, the review moves on to explore the therapeutic potentials of liposomal nanocarriers in treating liver cirrhosis, fibrosis, viral hepatitis, and hepatocellular carcinoma. Through discussing recent advancements and envisioning future perspectives, this review highlights the role of liposomal nanocarriers in enhancing the effectiveness and the safety of liver disorders and consequently improving patient outcomes and enhances life quality.