Journal of Liposome Research最新文献

The aim of this study was to develop novel cubosomes as an oral delivery system to improve the permeation and anti-clotting activity of Rivaroxaban (RX). The experimental design (2³ full factorial design) was employed to study individual and combined impacts of the assigned formulation variables. The variables RX amount (X₁), Poloxamer (PX): GMO (GMO) ratio (X₂) and PX/GMO: water ratio (X₃) were taken as independent factors, and their effect was examined on entrapment efficiency (Y₁), particle size (Y₂), and zeta potential. (Y₃). The cubosomal vesicle RX-C 3 composed of RX (20 mg), PX: GMO (1:0.5 % w/w), and PX/GMO: water (1:5% w/w) is the optimised formula achieving the required prerequisites. RX-C 3 had shown a vesicle size of 91.2 ± 1.3 nm, entrapment efficiency of 96.27 ± 0.12 %, and zeta potential of -24.1 ± 0.2 mV. The in-vivo studies showed revealed good inhibition of blood clotting, where RX-C 3 significantly increased clotting time by 35% and prothrombin time by 29% compared to Rivarospire^®. In conclusion, the present study suggested that oral cubosomes formulations provide prolonged delivery of Rivaroxaban.

Some breast cancers are caused by hormonal imbalances, such as estrogen and progesterone. These hormones play a function in directing the growth of cancer cells. The hormone receptors in hormone receptor-positive breast cancer lead breast cells to proliferate out of control. Cancer therapy such as hormonal, targeted, radiation is still unsatisfactory because of these challenges namely multiple drug resistance (MDR), off-targeting, severe adverse effects. A novel aromatase inhibitor exemestane (Exe) exhibits promising therapy in breast cancer. This study aims to develop and optimize Exe-loaded lipid nanocapsules (LNCs) by using DSPC, PF68 and olive oil as lipid, surfactant and oil phase, respectively and to characterize the same. The prepared nanocapsules were investigated via in vitro cell culture and in vivo animal models. The LNCs exhibited cytotoxicity in MCF-7 cell lines and enhanced anti-cancer activity and reduced cardiotoxicity in DMBA-induced animal model when compared to the drug. Additionally, in vivo pharmacokinetics revealed a 4.2-fold increased oral bioavailability when compared with Exe suspension. This study demonstrated that oral administration of Exe-loaded LNCs holds promise for the antiestrogenic activity of exemestane in breast cancer.

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated in vitro, ex-vivo, and in vivo parameters along with a comparison to it's commercial counterpart. The optimised ethosomes-based HA gel formulation revealed required pH (6.9 ± 0.2), small globule size (1024 ± 9 nm), zeta potential of -6.39 ± 0.2 mV, and 98 ± 1.1% HA content. The ex vivo skin permeation and deposition potenwere conferred on synthetic membrane Strat-M, Human cadaver skin, mice skin, rat skin, and pig skin, and both parameters were found to be much higher in comparison to the commercial topical formulation. Skin deposition capacity of the optimised HA formulation was further confirmed by Scan Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) and it was observed that the developed ethosomal gel formulation got deposited more on the treated skin. The in vivo anti-ageing effect of optimised ethosomal gel on rats was found to be greater when compared to commercial formulation of HA and the developed carrier-based system proved to deliver the HA molecule in very small amounts into the systemic circulation. The results endorse the ethosomal carrier-based formulation of HA as a attractive technique for better local bioavailability of HA.

Dry eye disease (DED) is a worldwide, multifactorial disease mainly caused by a deficit in tear production or increased tear evaporation with an increase in tear osmolarity and inflammation. This causes discomfort and there is a therapeutic need to restore the homeostasis of the ocular surface. The aim of the present work was to develop a biodegradable and biocompatible liposomal formulation from the synthetic phospholipids 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) that is able to reduce the effects of hypertonic stress by helping to restore the lipid layer of the tear film. Liposomes were made using the lipid film hydration method with synthetic phospholipids (10 mg/mL) with and without 0.2% HPMC. They were characterised in terms of size, osmolarity, pH, surface tension, and viscosity. Additionally, the in vitro toxicity of the formulation at 1 and 4 h in human corneal epithelial cells (hTERT-HCECs) and human conjunctival cells (IM-HConEpiC) was determined. Furthermore, osmoprotective activity was tested in a corneal model of hyperosmolar stress. In vivo acute tolerance testing was also carried out in albino New Zealand rabbits by topical application of the ophthalmic formulations every 30 min for 6 h. All the assayed formulations showed suitable physicochemical characteristics for ocular surface administration. The liposomal formulations were well-tolerated in cell cultures and showed osmoprotective activity in a hyperosmolar model. No alterations or discomfort were reported when they were topically administered in rabbits. According to the results, the osmoprotective liposomal formulations developed in this work are promising candidates for the treatment of DED.

The membrane of a cell separates the internal and external media of the cell and contributes to a variety of important processes, including gradient maintenance and signal transduction. Synthetic lipid-made vesicles are commonly utilized as cell membrane model systems. These could be liposomes or giant unilamellar vesicles (GUVs) in most cases. Liposomes are typically less than 0.5 microns in size, limiting their use for most microscopy experiments. GUVs are a form of liposomes that ranges in size from 5 to 200 microns and are ideal for examining complex phase behaviors of biomembranes using the classical optical setting. This study details the step-by-step development of a portable, light and low-cost kit for generating GUVs by electroformation. Our kit contains an in-built electronic circuitry, and the GUV generation setup, consisting of 3 ITO-coated glasses with heating electrode connections. Approximately 600 µl of GUVs can be produced in one experiment, while the amount could be increased by changing the dimensions of the GUV generation setup. Finally, the originality of the study comes from the fact that many users from different fields unfamiliar with electronics can use our home-built cost-effective approach instead of their expensive commercial counterparts.

Abiraterone acetate (ABRTA) is clinically beneficial in management of metastatic castration-resistant prostate cancer (PC-3). With highlighted low solubility and permeability, orally hampered treatment of ABRTA necessitate high dose to achieve therapeutic efficacy. To triumph these challenges, we aimed to develop intestinal lymphatic transport facilitating lipid-based delivery to enhance bioavailability. ABRTA-containing self-nano emulsified drug delivery (ABRTA-SNEDDS) was statistically optimized by D-optimal design using design expert. Optimized formulation was characterized for particle size, thermodynamic stability, in vitro release, in vivo bioavailability, intestinal lymphatic transport, in vitro cytotoxic effect, anti-metastatic activity, and apoptosis study. Moreover, hemolysis and histopathology studies have been performed to assess pre-clinical safety. Nano-sized particles and successful saturated drug loading were obtained for optimized formulation. In vitro release upto 98.61 ± 3.20% reveal effective release of formulation at intestinal pH 6.8. ABRTA-SNEDDS formulation shows enhanced in vivo exposure of Abiraterone (2.5-fold) than ABRTA suspension in Sprague-Dawley rats. In vitro efficacy in PC-3 cell line indicates 3.69-fold higher therapeutic potential of nano drug delivery system. Hemolysis and histopathology study indicates no significant toxicities to red blood cells and tissues, respectively. Apparently, an opportunistic strategy to increasing bioavailability of ABRTA via intestinal lymphatic transport will create a viable platform in rapidly evolving chemotherapy. Enhanced translational utility of delivery was also supported through in vitro therapeutic efficacy and safety assessments. HighlightsAbiraterone acetate is a prostate cancer drug, impeded with low bioavailability.ABRTA loaded in self nano emulsifying drug delivery enhanced its bioavailability.Intestinal lymphatic transport played role in enhanced bioavailability of ABRTA.ABRTA-SNEDDS enhanced in vitro cytotoxic activity of ABRTA.ABRTA-SNEDDS found safe in preclinical safety evaluations.

Ovarian cancer is a serious threat to female health, although the incidence of it is relatively low, its mortality rate remains high due to its intense invasion and metastasis. Therefore, it is urgent to explore new treatment strategies for ovarian cancer. In this study, paclitaxel and emodin were encapsulated in different micelles, and loaded on the surface of the micelles with epidermal growth factor (EGF) as the targeting molecule, made compound formulations in proportion. In this study, EGF-modified paclitaxel micelles and EGF-modified emodin micelles were characterized, their inhibitory effects on SKOV3 cell proliferation and invasion were studied in vivo and in vitro, and its targeting ability was confirmed. The results showed that the shape, particle size, zeta potential, release rate, encapsulation rate, polydispersity index, and other physical and chemical properties of EGF-modified paclitaxel micelles plus EGF-modified emodin micelles meet the requirements, and the modification of EGF on the micelle surface could obviously improve the uptake of SKOV3 cells and inhibit the proliferation of SKOV3 cells. The compound formulation can inhibit the invasion and metastasis of ovarian cancer by inhibiting the expression of hypoxia inducible factor-α, MMP-2, MMP-9, and VE-cadherin. The in vivo studies have also showed significant pharmacodynamics results. These results indicated that EGF-modified paclitaxel micelles plus EGF-modified emodin micelles provide a new strategy for the treatment of ovarian cancer.

At the dawn of a new nanotechnological era in the pharmaceutical field, it is very important to examine and understand all the aspects that influence in vivo behaviour of nanoparticles. In this point of view, the interactions between serum proteins and liposomes with incorporated anionic, cationic, and/or PEGylated lipids were investigated to elucidate the role of surface charge and bilayer fluidity in protein corona's formation. 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), hydrogenated soybean phosphatidylcholine (HSPC), and 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) liposomes with the presence or absence of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (chloride salt) (DOTAP), and/or 1,2-dipalmitoylsn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DPPE-PEG 5000) lipids were prepared by the thin-film hydration method. The evaluation of their biophysical characteristics was enabled by differential scanning calorimetry and dynamic and electrophoretic light scattering. The physicochemical characteristics of mixed liposomes were compared before and after exposure to foetal bovine serum (FBS) and were correlated to calorimetric data. Our results indicate protein binding to all liposomal formulations. However, it is highlighted the importance of surface charge and fluidisation effect to the extent of protein adsorption. Additionally, considering the extensive use of cationic lipids for innovative delivery platforms, we deem PEGylation a key parameter, because even in a small proportion can reduce protein binding, and thus fast clearance and extreme toxicity without affecting positive charge. This study is a continuation of our previous work about protein-liposome interactions and fraction of stealthiness (Fs) parameter, and hopefully a design road map for drug and gene delivery.