Journal of Liposome Research最新文献

Development of AS1411aptamer-conjugated liposomes for targeted delivery of arsenic trioxide is the primary goal of this study. AS1411aptamer was used as ligand to target nucleolin, which is highly expressed on the surface of melanoma cancer cells. The targeted liposomes were constructed by the thin film method, and arsenic trioxide was loaded as cobalt (II) hydrogen arsenite (CHA) to increase the loading efficiency and stability of the liposomes. The liposomal structure was characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM). In addition, particle sizes and zeta potential of the CHA-loaded liposomes (CHAL) and aptamer-functionalized CHA-loaded liposomes (AP-CHAL) were determined. In vitro cytotoxicity of CHAL and AP-CHAL were evaluated using MTT assay in murine melanoma (B16) and mouse embryonic fibroblast (MEF) cell lines. The encapsulation efficiency of CHAL and AP-CHAL was reported as 60.2 ± 6.5% and 58.7 ± 4.2%, respectively. In vivo antitumor activity of CHAL and AP-CHAL in the B16 tumor-xenograft mouse model was dramatically observed. All mice of both groups survived until the end of treatment and showed body weight gain. The tumor protrusion completely disappeared in 50% of the mice in these groups. Furthermore, histopathology studies demonstrated that CHAL and AP-CHAL did not induce significant toxicity in healthy mice tissues. However, unlike the CHAL group, which showed an initial increase in tumor volume, a specific antitumor effect was observed in the AP-CHAL group from the beginning of treatment. The results showed that AP-CHAL can be used as an effective drug delivery system with high potential in the treatment of solid tumors.

Cancer has been characterized by abnormal and uncontrolled proliferation of cells. Majority of drugs given through chemotherapy produce unwanted and adverse effects of chemotherapeutic agents to the other healthy cells and tissues of body. Various nanocarriers have now been considered for treatment of cancer. Among various nanocarriers, cubosomes are the nano sized dispersions that have drawn interest of researchers recently. Cubosomes are defined as dispersions of colloidal nature containing cubic crystalline liquid formations in aqueous medium in presence of suitable surfactant molecules. The unique capacity to encapsulate lipophilic, hydrophilic, and amphiphilic compounds inside their structure distinguishes them among others. Top- down method and hydrotrope method are most often employed methods for cubosomes preparation. Cubosomes can be characterized by Polarized light microscopy Photon correlation spectroscopy X-ray scattering (SAXS), Transmission electron microscopy and various stability studies. Cubic lipid nanoparticles have a very stable cubic structure that enables slower dissociation rate, increased retention and site-specific delivery of drugs. Cubosomes containing extracts of cornelian cherry for boosting anti-cancerous effects in cancer of colorectal cells by preventing against GIT destruction. When applied for skin cancer, cubosomes have shown to be having enhanced permeation of the drug. In liver cancer, increased bioavailability of drug was observed via cubosomes. This current review elaborates the advancement of cubosomes and their effective role in the treatment of cancer. This review aims to describe vesicular approach of cubosomes, its composition and method of preparation, characterization tests as well as elaborates various applications of cubosomes in cancer.

To develop a PEGylated and CD44-targeted liposomes, enabled by surface coating with hyaluronic acid (HA) via amide bond to improve the efficacy of imatinib mesylate (IM), for tumor-targeted cytoplasmic drug delivery. HA was covalently grafted on DSPE-PEG2000-NH2 polymer. HA-modified or unmodified PEGylated liposomes were prepared with ethanol injection method, and the stability, drug release, and cytotoxicity of these liposomes were studied. Meanwhile, intracellular drug delivery efficiency, antitumor efficacy, and pharmacokinetics were also investigated. Ex vivo fluorescence biodistribution was also detected by small animal imaging. In addition, endocytosis mechanism was also explored HA-coated PEGylated liposomes (137.5 nm ± 10.24) had a negative zeta potential (-29.3 mV ± 5.44) and high drug loading (27.8%, w/w). The liposomes were stable with cumulative drug leakage (<60%) under physiological conditions. Blank liposomes were nontoxic to Gist882 cells, and IM-loaded liposomes had higher cytotoxicity to Gist882 cells. HA-modified PEGylated liposomes were internalized more effectively than non-HA coating via CD44-mediated endocytosis. Besides, the cellular uptake of HA-modified liposomes also partly depends on caveolin-medicated endocytosis and micropinocytosis. In rats, both liposomes produced a prolonged half-life of IM (HA/Lp/IM: 14.97h; Lp/IM: 11.15h) by 3- to 4.5-folds compared with the IM solution (3.61h). HA-decorated PEGylated liposomes encapsulated IM exhibited strong inhibitory effect on tumor growth in Gist882 cell-bearing nude mice and formation of 2D/3D tumor spheroids. The Ki67 immunohistochemistry result was consistent with the above results. IM-loaded PEGylated liposomes modified with HA exerted the excellent anti-tumor effect on tumor-bearing mice and more drugs accumulated into the tumor site.

Small biospecific peptides with defined chemical structure and cellular responses are promising alternatives to full-length therapeutic proteins. Identification of these peptides solely or in combination with other bioactive factors and determination of their targets are of substantial interest in current drug delivery research. This study is aimed at the development of new liposomal formulations of ECM-derived GHK peptide known for its multiple regeneration-related activities but poorly recognized cellular targets. In situ association of membranotropic GHK derivative with unilamellar liposomes was performed to prepare GHK-modified liposomes with defined properties. According to DLS, the GHK component on the liposomal surface interacted with heparin in a specific manner compared to other polysaccharides and RGD counterpart, whereas ITC analysis of such interactions was complicated. The results provide a useful tool for screening of bio-interactions of synthetic peptide-presenting liposomes by the DLS technique. They were also employed to produce a multi-functional nanosized GHK-heparin covering for liposomes. The resulting composite liposomes possessed low size dispersity, increased anionic charge, and mechanical rigidity. The heparin component significantly promoted the accumulation of GHK-modified liposomes in 3T3 fibroblasts so that the composite liposomes exhibited the highest cell-penetrating activity. Furthermore, the latter formulation stimulated cell proliferation and strongly inhibited ROS production and GSH depletion under oxidative stress conditions. Together, the results support that cell-surface glycosaminoglycans can be involved in GHK-mediated liposomal delivery, which can be further greatly enhanced by association with heparin. The composite liposomes with GHK-heparin covering can be considered as an advanced GHK-based formulation for therapeutic and cosmeceutical applications.

Upon in vivo administration of nanoparticles, a protein corona forms on their surface and affects their half-life in circulation, biodistribution properties, and stability; in turn, the composition of the protein corona depends on the physico-chemical properties of the nanoparticles. We have previously observed lipid composition-dependent in vitro and in vivo microRNA delivery from lipid nanoparticles. Here, we carried out an extensive physico-chemical characterisation to understand the role of the lipid composition on the in vivo fate of lipid-based nanoparticles. We used a combination of differential scanning calorimetry (DSC), membrane deformability measurements, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS) to probe the interactions between the nanoparticle surface and bovine serum albumin (BSA) as a model protein. The lipid composition influenced membrane deformability, improved lipid intermixing, and affected the formation of lipid domains while BSA binding to the liposome surface was affected by the PEGylated lipid content and the presence of cholesterol. These findings highlight the importance of the lipid composition on the protein-liposome interaction and provide important insights for the design of lipid-based nanoparticles for drug delivery applications.

Drug delivery through transdermal route is one of the effective methods for the application of drugs. It overcomes many drawbacks which are encountered with the oral route. Moreover, many drugs are not able to pass through the stratum corneum, which is the main barrier for the transdermal drug delivery. Formation of ultra-deformable vesicles (UDVs) is a novel technique for the transdermal applications of the drugs. Transethosomes (TEs), ethosomes, and transferosomes are all part of the UDV. Because of the presence of increased concentrations of ethanol, phospholipids, and edge activators, TEs provide improved drug permeation through the stratum corneum. Because of the elasticity of TEs, drug penetration into the deeper layer of skin also increases. TEs can be prepared using a variety of techniques, including the cold method, hot method, thin film hydration method, and the ethanol injection method. It increases patient adherence and compliance because it is a non-invasive procedure of administering drugs. Characterization of the TEs includes pH determination, size and shape, zeta potential, particle size determination, transition temperature, drug content, vesicle stability, and skin permeation studies. These vesicular systems can be utilized to deliver a variety of medications transdermally, including analgesics, antibiotics, antivirals, and anticancer and arthritis medications. This review aims to describe vesicular approaches that had been used to overcome the barrier for the transdermal delivery of drug and also describes brief composition, method of preparation, characterization tests, mechanism of penetration of TEs, as well as highlighted various applications of TEs in medicine.

Spherical structures built from uni- and multilamellar lipid bilayers (LUV and MLV) are nowadays considered not just as nanocarriers of various kinds of therapeutics, but also as the vehicles that, when coupled with gold (Au) nanoparticles (NPs), can also serve as a tool for imaging and discriminating healthy and diseased tissues. Since the presence of Au NPs or their aggregates may affect the properties of the drug delivery vehicle, we investigated how the shape and position of Au NP aggregates adsorbed on the surface of MLV affect the arrangement and conformation of lipid molecules. By preparing MLVs constituted from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in the presence of uncoated Au NP aggregates found i) both within liposome core and on the surface of the outer lipid bilayer, or ii) adsorbed on the outer lipid bilayer surface only, we demonstrated the maintenance of lipid bilayer integrity by microscopic techniques (cryo-TEM, and AFM). The employment of SERS and FTIR-ATR techniques enabled us not only to elucidate the lipid interaction pattern and their orientation in regards to Au NP aggregates but also unequivocally confirmed the impact of Au NP aggregates on the persistence/breaking of van der Waals interactions between hydrocarbon chains of DPPC.

Liposomes are spherical lipidic nanocarriers composed of natural or synthetic phospholipids with a hydrophobic bilayer and aqueous core, which are arranged into a polar head and a long hydrophobic tail, forming an amphipathic nano/micro-particle. Despite numerous liposomal applications, their use encounters many challenges related to the physicochemical properties strongly affected by their constituents, colloidal stability, and interactions with the biological environment. This review aims to provide a perspective and a clear idea about the main factors that regulate the liposomes' colloidal and bilayer stability, emphasising the roles of cholesterol and its possible alternatives. Moreover, this review will analyse strategies that offer possible approaches to provide more stable in vitro and in vivo liposomes with enhanced drug release and encapsulation efficiencies.