Journal of Liposome Research最新文献

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.

Personalized treatment strategies have greatly improved the efficacy of anticancer drugs. Nanocarriers, especially liposomes, function as excellent platform for the delivery of both hydrophilic and hydrophobic agents. iRGD is a peptide composed of 9-amino acid denoted as (iRGDP), enhances selective and intratumoral delivery of anticancer drugs. Trastuzumab (TMAB), mainly targets HER2-positive advanced stage breast cancer is an FDA-approved monoclonal antibody. Gefitinib (GEB) is an anticancer drug, effective against metastatic breast cancer (MBC), while Lycorine hydrochloride (LCOH), a naturally derived compound, possess both anti-inflammatory and anticancer properties. This research is mainly emphasizing on the preparation of GEB and LCOH-entrapped TPGS-COOH coated-liposomes, camouflaged with an antibody (TMAB) and cyclic peptide (iRGDP) for targeted delivery in MBC therapy. The developed multifunctional liposomes were studied for extensive in vitro cell line studies on MCF-7 cells. The half-maximum inhibitory concentration (IC-50) values of GEB and LCOH co-loaded single functionalized liposome (SFL) (iRGDP-LiP, and TMAB-LiP) and dual-functionalized liposome (DFL) (iRGDP-TMAB-LiP) on MCF-7 cells were 1.04 ± 0.023 μg/mL, 0.71 ± 0.018 μg/mL, and 0.56 ± 0.028 μg/mL, respectively. Inverted confocal laser scanning microscopy (ICLSM) revealed enhanced cellular internalization in SFL and DFL-treated groups tagged with coumarin-6 and rhodamine-B dye as compared to conventional liposome. The scratch assay revealed a marked reduction in cell migration, while DAPI staining confirmed enhanced nuclear condensation (NC) and nuclear fragmentation (NF) in SFL and DFL-treated groups. Moreover, flow cytometry demonstrated enhanced early and late apoptosis in SFL and DFL groups. These findings indicate that GEB and LCOH co-loaded multifunctional liposome holds promise as a multifaceted therapeutic approach for MBC therapy.

Giant liposomes, or giant unilamellar vesicles (GUVs), have been utilized as cell-size bioreactors to replicate the physical and chemical properties of biological cells. However, conventional methods for preparing GUVs typically lack precise control over their size. Several research groups have recently developed microfluidic techniques to create monodisperse GUVs by generating water-in-oil-in-water (W/O/W) droplets with a thin oil layer that subsequently transform into GUVs. However, the formation of a thin oil shell requires the intricate control of the flow rate, which can be both challenging and unstable. In this study, we investigated the design of a two-step flow-focusing microfluidic channel to produce stable W/O/W droplets. These droplets underwent substantial oil layer reduction through spontaneous removal by fluidic shear forces. Consequently, the majority of the oil layer in the W/O/W droplets was reduced, improving uniformity of GUVs.

Vesicular nanocarriers like niosomes and liposomes are widely researched for controlled drug delivery systems, with niosomes emerging as promising alternatives due to their higher stability and ease of manufacturing. This study aimed to develop and characterize a niosomal formulation for the encapsulation and sustained release of temozolomide (TMZ), a model lipophilic drug, and to compare the stability of niosomes and liposomes, with a particular focus on the behavior of their lipid bilayers. Niosomes were prepared using the thin-film hydration method, composed of Span 60 (Sorbitan monostearate), cholesterol, and soy lecithin in varying molar ratios. The study investigated critical properties such as drug loading capacity, release kinetics, and resistance to enzymatic degradation. The optimized formulation was analyzed for drug entrapment efficiency and stability against phospholipase A₂ (PLA₂) degradation. The optimized niosomal formulation, with a 4:2:1 molar ratio of Span 60: cholesterol, achieved a high TMZ entrapment efficiency of 73.23 ± 1.02% and demonstrated sustained drug release over 24 hours. In comparison, liposomes released their TMZ payload within 4 hours upon exposure to PLA₂, while the niosomes maintained their release profile, indicating superior stability. Spectroscopic and thermal analysis confirmed successful drug encapsulation with no component incompatibilities.

Carnosine is an endogenous dipeptide characterized by a multimodal mechanism of action. However, its clinical potential is limited by serum and cytosolic carnosinases, which significantly reduce its bioavailability. Based on that, different research groups have worked on the development of new strategies able not only to prevent its rapid metabolization but also to improve its distribution and specific targeting. In the present study, the development and in vitro characterization of new liposomal formulations loaded with carnosine are described. Nanoliposomes, produced through Thin-Layer Hydration followed by Extrusion method, were first investigated for their physicochemical stability. Photon correlation spectroscopy and electrophoretic light scattering, assessing the stability of the formulations, showed a strong homogeneity-oriented tendency for up to two months. Particle size, polydispersity index, and zeta potential were determined through dynamic light scattering and electrophoretic light scattering, demonstrating an almost neutral charge of the formulation and an effective encapsulation of carnosine. The morphology assessment performed via scanning electron microscopy showed good conformity and polydispersity. Differential scanning calorimetry measurements suggest the ability of carnosine to stabilize the large unilamellar vesicles. Lastly, the newly developed carnosine-loaded liposomal formulations also showed a good safety profile in human microglia.

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.

Lymphography is a useful technique in the diagnosis of lymphatic diseases. Conventional lymph node imaging methods, such as subcutaneous and footpad injections, are invasive and unable to visualize mesenteric lymph nodes. Liposomes have the potential to increase the oral bioavailability of poorly bioavailable hydrophilic drugs and promote their lymphatic transport in the intestinal lymph. In this study, the iohexol liposome was prepared using cholesterol, soybean lecithin, and iohexol by the reverse-phase evaporation method. It had an encapsulation efficiency of 70.26%, an average particle size diameter of 185.7 nm, a polydispersity index of 0.275, and a zeta potential of -7.697 mV. The iohexol liposomes were stable for five days at 4 °C under static conditions. The iohexol content in the lymph nodes of mice after oral iohexol liposomes initially increased and then gradually decreased over time, with the absorption peak occurring around 50-70 minutes and a peak iohexol content of 5.09 mg/g. After oral administration of iohexol liposomes, mild enhancement (12.46-12.92 HU) was observed in the mesenteric lymph nodes of dogs through CT scanning after a certain period. These results indicate that iohexol liposomes, when administered orally, can effectively achieve imaging of the mesenteric lymph nodes. Overall, we provide a novel noninvasive imaging modality based on liposomes for evaluating mesenteric lymph nodes via lymphography.

This study describes the development of a novel liposomal formulation incorporating 3-O-ethyl-L-ascorbic acid (EAA), a derivative of vitamin C. The EAA-loaded liposomes were fully characterized, particle size and zeta potential values suitable for drug delivery. The skin penetration studies revealed that liposomal formulation enhanced EAA retention in the skin compared to free EAA. Additionally, the impact of topical treatments with liposomal EAA on photo-aging markers in skin explants was investigated. EAA charged liposomes display a protective or stimulatory effect on cellular metabolism. Finally, liposomal EAA have a significant effect on the inflamatory markers, reducing the extracellular matrix degradation associated with UV-induced damage of skin. These findings provide valuable insights into the potential of liposomal formulations for the development of advanced cosmetic products.

The aim of this study was to load 4-farnesyloxycoumarin (4-FLC) in nanoliposomes (4-FLC-LNPs) and evaluate its anti-cancer and anti-metastatic effects. 4-FLC-LNPs were synthesized using a combination of lecithin-cholesterol-polyethylene glycol. The physicochemical properties were evaluated using DLS, FTIR, and microscopy methods. The toxicity against breast cancer (MCF-7), prostate cancer (PS3), pancreatic cancer (PANC), gastric cancer (AGS), and normal cell lines (HUVEC) was evaluated using the MTT assay. Fluorescent staining and flow cytometry were used to assess the occurrence of apoptosis. Molecular analysis methods were used to study the apoptosis and metastasis effects of these nanoliposomes. The antioxidant power of 4-FLC-LNPs was measured using the ABTS and DPPH free radicals methods. 4-FLC-LNPs exhibit a spherical morphology, with an average size of 57.43 nm, a polydispersity index of 0.29, and a zeta potential of -31.4 mV. They demonstrate an encapsulation efficiency of 82.4% for 4-FLC. The IC50 value of 4-FLC-LNPs against the breast cancer cell line was reported as the most sensitive, at approximately 60 μg/mL. ABTS and DPPH results were reported at approximately 30 µg/mL. The inductive effects of nanoliposomes on the apoptosis process were confirmed by an increase in the number of apoptotic cells, as well as the arrest of cells in various phases of cell growth. The increased expression of BAX and decreased expression of Bcl-2, MMP-2, and MMP-9 confirmed the pro-apoptotic and anti-metastatic effects of 4-FLC-LNPs. These finding validate the therapeutic potential of 4-FLC-LNPs, which may be utilized in preclinical studies.

This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing in-situ nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 3² full-factorial design. Size, morphology, zeta potential, ex-vivo permeation, and in-vitro release were estimated. The surface of optimized liposome was modified with ascorbic acid. The size of surface-modified liposomes was bigger (191.4 nm) than the unmodified liposomes (171 nm). Surface-modified liposomes were embedded in in-situ gel using poloxamer and Carbopol 934P. Liposomal in-situ gel showed higher permeation (71.94%) in contrast to the plain gel (46.64%). In-vivo pharmacokinetic examination of payload from liposomal in-situ gel displayed higher concentration in brain (C_max of 93.50 ng/mL). The liposomal in-situ nasal gel had a higher drug targeting efficiency (138.43%) and a higher drug targeting potential (27.77%) confirming improved brain targeting. In male Wistar rats, the pharmacodynamic parameters (path length and escape latency) were evaluated with trimethyl tin-induced neurodegeneration. Animals treated with BER-loaded in-situ gel significantly decreased escape latency and path length in comparison to the control group. Histopathological assessment showed that the formulated gel was safe for intranasal administration. The developed formulation has the potential to effectively enhance the efficacy of BER in Alzheimer's disease management.