Patent US6706861 - Reconstitution of purified membrane proteins into preformed liposomes - Google Patents
The present application relates to a method of making liposomes having membrane proteins incorporated therein, the method comprising: providing the membrane protein in solution; providing a solution of preformed liposomes; and incubating the mixture. Prior to the step of providing a solution of preformed liposomes, the liposomes are formed by combining a mixture of phospholipids with a solution of at least one type of unsaturated fatty acid. The methods of the present invention further relate to the method of making a reagent comprising tissue factor reconstituted into preformed liposomes. The method of the present invention for making a tissue factor reagent comprises: providing tissue factor in solution; providing a solution of preformed liposomes comprising a mixture of phospholipids and at least one type of unsaturated fatty acid; and incubating the mixture.http://www.google.com/patents/US6706861?dq=5,960,411
Efficacy and Safety of A Liposome-Based Vaccine against Protein Tau, Assessed in Tau.P301L Mice That Model Tauopathy
Progressive aggregation of protein Tau into oligomers and fibrils correlates with cognitive decline and synaptic dysfunction, leading to neurodegeneration in vulnerable brain regions in Alzheimer's disease. The unmet need of effective therapy for Alzheimer's disease, combined with problematic pharmacological approaches, led the field to explore immunotherapy, first against amyloid peptides and recently against protein Tau. Here we adapted the liposome-based amyloid vaccine that proved safe and efficacious, and incorporated a synthetic phosphorylated peptide to mimic the important phospho-epitope of protein Tau at residues pS396/pS404. We demonstrate that the liposome-based vaccine elicited, rapidly and robustly, specific antisera in wild-type mice and in Tau.P301L mice. Long-term vaccination proved to be safe, because it improved the clinical condition and reduced indices of tauopathy in the brain of the Tau.P301L mice, while no signs of neuro-inflammation or other adverse ...http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072301
Patent US4370349 - Process for preparing freeze-dried liposome compositions - Google Patents
Process for preparing a freeze-dried, potential liposome, mixture which comprises either (a) dissolving at least one liposome-forming amphipathic lipid, at least one biologically-active compound, and optionally one or more adjuvants, in a suitable solvent, and then freeze-drying the solution, or (b) preparing by any known method an aqueous liposome composition containing at least one biologically-active compound, and then freeze-drying the said aqueous liposome composition. Process for preparing an aqueous liposome composition which comprises dispersing said freeze-dried, potential liposome, mixture, obtained by procedure (a) or (b), in a suitable aqueous medium.http://www.google.com/patents/US4370349?dq=6,563,928
Influence of poly(ethylene glycol) grafting density and polymer length on liposomes : Relating plasma circulation lifetimes to...
The incorporation of poly(ethylene glycol) (PEG)-conjugated lipids in lipid-based carriers substantially prolongs the circulation lifetime of liposomes. However, the mechanism(s) by which PEG-lipids achieve this have not been fully elucidated. It is believed that PEG-lipids mediate steric stabilization, ultimately reducing surface-surface interactions including the aggregation of liposomes and/or adsorption of plasma proteins. The purpose of the studies described here was to compare the effects of PEG-lipid incorporation in liposomes on protein binding, liposome-liposome aggregation and pharmacokinetics in mice. Cholesterol-free liposomes were chosen because of their increasing importance as liposomal delivery systems and their marked sensitivity to protein binding and aggregation. Specifically, liposomes containing various molecular weight PEG-lipids at a variety of molar proportions were ...http://uu.diva-portal.org/smash/record.jsf?pid=diva2:38872
A pharmacokinetic and MRI study of unilamellar gadolinium-, manganese-, and iron-DTPA-stearate liposomes as organ-specific...
Small unilamellar liposomes that contain the lipophilic chelate DTPA-stearate (DTPASA) were used as carriers for the paramagnetic metal ions gadolinium, manganese, and iron. The iron liposomes were unstable in vitro and thus not studied further. The natural targeting properties of these liposomes to the reticuloendothelial system was used in rats and dogs for the imaging of liver and spleen. In vitro incubations with human plasma, followed by high-pressure liquid chromatography (HPLC) separation of the Gd-DTPASA and Mn-DTPASA liposomes showed that after an incubation period of 24 hours, only 4% of the gadolinium was bound to the plasma proteins, whereas, with the Mn-DTPASA liposomes, a transfer of 40% manganese was seen. These results indicate that the Mn-DTPASA complex is not stable. On T1-weighted images, both liposome preparations gave a strong signal enhancement of the organs of the ...http://www.zora.uzh.ch/id/eprint/23345/
Fluorescent Liposomes - Fluorescent Liposomes (Encapsulated dyes) - FormuMax Scientific, Inc.
Fluorescent Liposomes (Encapsulated dyes). Soluble fluorescent dyes are encapsualted inside liposomes. The free external dye is removed to less than 1%. ...http://www.liposomeexpert.com/categories/fluorescent-liposomes/fluorescent-liposomes-encapsulated-dyes.html
Pharmaceutical info: Prolonged release drug delivery system of pilocarpine nitrate
Surface potential can play an important role in the behavior of liposomes in vivo and in vitro. In general charged liposomes were more stable against aggregation and fusion than uncharged liposomes. However physically stable neutral liposomes have been described. The inclusion of negatively charged lipid such as stearylamine tends to increase the entrapped volume. [Table 1] shows the percent drug entrapment in various liposome formulations. [Table 2] shows the release of pilocarpine nitrate from neutral, negative and positively charged liposomes. The release kinetics was found to be first order initially followed by mixed order. More drug was released from charged liposomes than the neutral liposomes [Table 3] and [Table 4], [Figure 2]. A prolonged duration of response was observed during in vivo studies of liposome formulation. Positively charged ...http://niazi-pharmaceuticalinfo.blogspot.de/2010/08/prolonged-release-drug-delivery-system.html
Abstract T P99: Development of Liposomes Loaded With Computed Tomogratphy Contrast Agent for Thrombus Imaging | Stroke
Introduction: Liposomes are the most established nanocarriers that can be loaded with contrast agents as well as tailored for targeting to the desired tissue. Targeted CT liposomes represent a novel approach for rapid thrombus imaging. They allow specific and selective accumulation in thrombus providing significant contrast enhancement (expressed as HU) over the surrounding tissue.. Hypothesis: We hypothesize that preparation technology will produce homogenous liposomes with sufficient level of loaded CT contrast agent.. Methods: Liposomes were composed of distearoyl phosphatidylcholine, cholesterol, and distearoyl phosphatidylethanolamine - polyethylene glycol 2000 (molar ratio, 55/45/5). CT liposomes were prepared by lipid film hydration with iohexol (Omnipaque 350, GE Healthcare) followed by freeze-thaw extrusion (100 nm). Subsequently, they were purified by dialysis (Slide-A-Lyzer, cut-off 10 kDa) to remove un-loaded ...http://stroke.ahajournals.org/content/46/Suppl_1/ATP99
OSA | Spectrofluorimetry and Chemometrics for Investigation of Norfloxacin Distribution in Multilamellar Liposomes
Norfloxacin (NFX), a fluoroquinolone, was encapsulated in multilamellar liposomes (MLV) of soy-bean phosphatidylcholine at pH 7.0. The observed affinity of this class of drugs for hydrophobic environments, such as phospholipid bilayers, could lead to a better understanding of the mechanism of uptake in bacteria. The fluorescent properties of NFX were examined both free in solution and in MLV, using anisotropy and fluorescence quenching measurements. The latter data was treated with a chemometric method to deconvolute the overlapped spectra of zwitterionic and neutral species of NFX in equilibrium at this pH. The results show that NFX incorporates into the lipidic bilayers with two different distributions of species: the zwitterionic form in the lipid/aqueous interface, and the neutral one, more towards the center of the bilayer.. PDF Article ...https://www.osapublishing.org/as/abstract.cfm?uri=as-59-8-1032
Evaluation of the high-pressure extrusion technique as a method for sizing plasmid DNA-containing cationic liposomes | Drug...
A promising strategy to improve the immunogenic potential of DNA vaccines is the formulation of plasmid DNA (pDNA) with cationic liposomes. In this respect, particle size may be of crucial importance. This study aimed at the evaluation of high-pressure extrusion as a method for sizing cationic liposomes after entrapment of pDNA. This is a well-known sizing method for liposomes, but so far, it has not been applied for liposomes that are already loaded with pDNA. Liposomes composed of egg PC, DOTAP, and DOPE with entrapped pDNA were prepared by the dehydration-rehydration method and subjected to various extrusion cycles, comparing different membrane pore sizes and extrusion frequencies. At optimized extrusion conditions, liposome diameter (Zave) and polydispersity index (PDI) were reduced from 560 nm and 0.56 to 150 nm and 0.14 respectively, and 35% of the pDNA was retained. Importantly, gel electrophoresis ...http://drugdeliverytechnology.leidenuniv.nl/publications/3283
Clinical development of liposome based drugs: formulation, characteriz | IJN
Clinical development of liposome based drugs: formulation, characterization, and therapeutic efficacy Hsin-I Chang1, Ming-Kung Yeh21Department of Biochemical Science and Technology, National Chia Yi University, Chiayi City, 2Institute of Preventive Medicine, National Defence Medical Center, Sanhsia, Taipei, TaiwanAbstract: Research on liposome formulations has progressed from that on conventional vesicles to new generation liposomes, such as cationic liposomes, temperature sensitive liposomes, and virosomes, by modulating the formulation techniques and lipid composition. Many research papers focus on the correlation of blood circulation time and drug accumulation in target tissues with physicochemical properties of liposomal formulations, including particle size, membrane lamellarity, surface charge, permeability, encapsulation volume, shelf time, and release rate. This review is mainly to compare the therapeutic effect of ...https://www.dovepress.com/clinical-development-of-liposome-based-drugs-formulation-characterizat-peer-reviewed-article-IJN
Liposome Drug Delivery Market - Global Industry Volume and Region Analysis - 2025 - BizPR.us | US Free Press Release and...
http://www.transparencymarketresearch.com/liposome-drug-delivery-market.html. The classification of liposomes is based on its structural properties or on the method of preparation used. Structurally, liposomes are classified into the following groups: multilamellar large vesicles (MLV), oligolamellar vesicles (OLV), unilamellar vesicles (UV), small unilamellar vesicles (SUV), medium-sized unilamellar vesicles (MUV), large unilamellar vesicles (LUV), giant unilamellar vesicles (GUV), and multivesicular vesicles (MVV). In terms of preparation method used, liposomes can be classified into the following types: reverse phase evaporation method for single or oligolamellar vescile (REV), multilamellar vesicles (MLV) made by reverse phase evaporation method, stable plurilamellar vesicles, (FATMLV) frozen and thawed, vesicles prepared by extrusion method (VET), ...http://bizpr.us/2017/08/04/liposome-drug-delivery-market-global-industry-volume-region-analysis-2025/
Effects of phosphatidylserine and cholesterol liposomes on the viability, motility, and acrosomal integrity of stallion...
Computer-assisted motion analyses (CASA) and flow cytometry were used to evaluate stallion spermatozoa prior to and after cryopreservation. Spermatozoa were pretreated with: (1) Hepes-buffered medium (SHB); (2) phosphatidylserine (PS) liposomes; or (3) liposomes composed of both PS and cholesterol (PSCH) prior to dilution in either SHB or skim milk-egg yolk extender (SMEY). After cooling to 5 degrees C in SHB, PS and PSCH pretreatment (23%). Spermatozoal motion parameters were higher for spermatozoa diluted in SMEY than dilution in SHB. In Experiment 2, motion parameters were compared for spermatozoa pretreated with PSCH liposomes and cryopreserved in either SMEY or a high salt-skim milk-egg yolk extender (CO). Spermatozoal motion characteristics were similar for all spermatozoal treatments after cooling at 5 degrees C. After cryopreservation, PSCH liposome-treated samples had higher percentages of motile spermatozoa than untreated samples ...https://www.semanticscholar.org/paper/Effects-of-phosphatidylserine-and-cholesterol-lipo-Wilhelm-Graham/24169b0af8e01a38d59edd0b46fe88fab25e8999
Fick's second law transformed: one path to cloaking in mass diffusion | Journal of The Royal Society Interface
This report aims to target already-existing systems that could enable the use of cloaking concepts in order to achieve control of three-dimensional processes, using coated spheres consisting of concentric layers of homogeneous isotropic diffusivity. Various applications already implicate the use of concentric bilayered vesicles, one example being liposomes used for drug delivery . Liposomes are concentric bilayered vesicles in which an aqueous volume containing a water-soluble drug is enclosed by a membranous lipid bilayer composed of natural or synthetic phospholipids. One popular type of liposomes, known as the stealth liposomes , are highly stable, long-circulating liposomes whereby polyethylene glycol has been used as the polymeric steric stabilizer . Stealth and other liposomes use the concept of 'invisibility' in order to hide and evade the immunosystem by coupling water-soluble polymers to ...http://rsif.royalsocietypublishing.org/content/10/83/20130106
Interactions of liposomes with dental restorative materials | NIOM
The in vitro adsorption and retention of liposomes onto four common types of dental restorative materials (conventional and silorane-based resin composites as well as conventional and resin-modified glass ionomer cements (GIC)) have been investigated due to their potential use in the oral cavity. Uncoated liposomes (positively and negatively charged) and pectin (low- and high-methoxylated) coated liposomes were prepared and characterized in terms of particle size and zeta potential. The adsorption of liposomes was performed by immersion, quantified by fluorescence detection, and visualized by fluorescence imaging and atomic force microscopy. Positive liposomes demonstrated the highest adsorption on all four types of materials likely due to their attractive surface charge. They also retained well (minimum 40% after 60 min) on both conventional resin composite and GIC even when exposed to simulated salivary flow. Although an ...http://niom.no/interactions-of-liposomes-with-dental-restorative-materials/
U.S. Patent: 5532001 - Stimulation of tanning by DNA fragments or single-stranded DNA - July 2, 1996
In one method, DNA fragments, of approximately 2-200 bases in length, or deoxynucleotides (single bases), are administered topically to the epidermis, either in a liposome preparation or in another appropriate vehicle, such as propylene glycol, in a quantity sufficient to enhance melanin production. As used herein, "DNA fragments" refers to single-stranded DNA fragments, double-stranded DNA fragments, a mixture of both single-and double-stranded DNA fragments, or deoxynucleotides. "Deoxynucleotides" refers to either a single type of deoxynucleotide or a mixture of different deoxynucleotides. The DNA fragments or deoxynucleotides can come from any appropriate source. For example, salmon sperm DNA can be dissolved in water, and then the mixture can be autoclaved to fragment the DNA. The fragments can additionally be UV-irradiated. The liposome preparation can be comprised of any liposomes which penetrate the stratum corneum and fuse with the cell membrane, ...http://www.everypatent.com/comp/pat5532001.html
Metastatic or castrate-resistant is the second-leading cause of cancer mortality in males. In the past 3 years, chemotherapies have extended survival, but efficacy is limited by dose-limiting toxicities due to suboptimal biodistribution. We address the lack of specificity and accumulation in Castrate Resistant Prostate Cancer (CRPC) by developing a unique nano-carrier for drug delivery: targeted fusogenic liposomes.. We have developed a platform whereby liposomes are formulated with fusion associated small transmembrane protein p14 displaying targeting ligands. The p14 protein catalyzes mixing of the liposomal bilayer with cell membranes to deliver the cargo directly into the cytoplasm, while the targeting ligand bombesin, allows for targeting to the Gastrin-releasing Peptide (GRPR) that is overexpressed in prostate cancer.. We hypothesized that this novel targeted fusogenic liposome formulation would significantly improve the biodistribution and efficacy of ...http://cancerres.aacrjournals.org/content/76/14_Supplement/2192
pH-sensitive immunoliposomes composed of dioleoylphosphatidyl-ethanolamine and oleic acid (8:2 molar ratio) mediated the delivery of the cytotoxic fragment A of diphtheria toxin to the cytoplasm of target L-929 cells. Free fragment A, fragment A encapsulated in antibody-free liposomes, or fragment A encapsulated in pH-insensitive immunoliposomes was not effective in the inhibition of the cellular protein synthesis. pH-sensitive immunoliposomes containing diphtheria fragment A were not toxic to nontarget diphtheria-resistant A31 cells or to nontarget diphtheria-sensitive Vero cells. Pretreatment of target L-929 cells with the weak bases NH4Cl or chloroquine, agents which raise the endosome/lysosome pH, blocked the cytotoxic effect of the pH-sensitive immunoliposomes containing fragment A. Excess free antibody or excess empty pH-sensitive immunoliposomes also blocked the cytotoxic effect. Since it is known ...http://cancerres.aacrjournals.org/content/47/3/735
Much of the work on liposomal drug delivery has focused on cancer treatment because conventionally delivered cancer chemotherapy has been far from satisfactory. Major problems with conventional chemotherapy are the inability of the drug to reach the tumor site at pharmacologically active concentrations, intrinsic as well as acquired cross-resistance to multiple chemotherapeutic agents, and toxicity that contributes to many of the treatment failures.. Doxorubicin encapsulated in long-circulating, PEGylated liposomes has proven to be more effective than the free drug in several tumor models, including murine tumors and human tumor xenografts, regardless of tumor type and site of implantation (27) . In all of the experiments conducted, the liposomal preparation clearly performed better than Free-Dox, and the peak tumor drug levels obtained by liposome delivery were at least 3-fold greater. Notable differences in toxicity between free drug and liposomal drug have also been ...http://clincancerres.aacrjournals.org/content/5/3/687
Lactose-based glycoconjugates with variable spacers for design of liver-targeted liposomes
Abstract: Asialoglycoprotein receptors are highly abundant on the hepatocyte surface and have specific binding sites for blood serum glycoproteins. Such discovery resulted in development of liver-targeted drug delivery systems because modification of the liposomal surface by carbohydrate derivatives results in an increase of endocytosis, which facilitates selective uptake of such systems by hepatocytes. In this study we have synthesized novel lactose derivatives containing a palmitic hydrophobic domain. They were used for modification of the liposome surface. Transfection activity of modified liposomes was analyzed on the HepG2 cell line (hepatocytes) and showed an increase in the transfection efficiency as compared to the non-modified liposomes. At the same time transfection activities of modified and non-modified liposomes were similar in the case of a non-hepatocyte cell line (293T). The novel lactose-based glycoconjugates may be a ...http://pbmc.ibmc.msk.ru/index.php/en/article/PBMC-2017-63-5-467-en
Endocytosis of liposomes bound to cell surface proteins measured by flow cytofluorometry | Biochemical Journal
A new technique for the quantification of cellular receptor-mediated endocytosis has been developed based on the analysis by flow cytometry of ligand-bearing liposomes containing the fluorochrome carboxyfluorescein. Carboxyfluorescein encapsulated at high concentrations in protein A-bearing liposomes is self-quenched. Binding and internalization of such liposomes by cells via antibodies directed towards membrane surface determinants results in the release of the liposome-encapsulated carboxyfluorescein into the cytoplasm causing an increase in cell-associated fluorescence. This increase can be quantified on a flow cytofluorometer. ...http://www.biochemj.org/content/214/1/189
Focused Ultrasound Hyperthermia Mediated Drug Delivery Using Thermosensitive Liposomes and Visualized With in vivo Two-Photon...
1. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46:6387-92 2. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul. 2001;41:189-207 3. Maeda H. Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J Controlled Release. 2012;164:138-44 4. Harrington KJ, Mohammadtaghi S, Uster PS, Glass D, Peters AM, Vile RG. et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res. 2001;7:243-54 5. Allen C. Why I'm holding onto hope for nano in oncology. Mol Pharm. 2016;13:2603-4 6. Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6:583-92 7. Tan Q, Saggar JK, Yu M, Wang M, Tannock IF. Mechanisms of drug resistance ...http://thno.org/v07p2718.htm
Wiring liposomes and chloroplasts to the grid with an electronic polymer.
We present a novel thylakoid based bio-solar cell capable of generating a photoelectric current of 0.7 µA/cm2. We have introduced an electro conductive polymer, PEDOT-S, to the thylakoid membrane. PEDOT-S intervenes in the photosynthesis, captures electrons from the electron transport chain and transfers them directly across the thylakoid membrane, thus generating a current. The incorporation of the electro conductive polymer into the thylakoid membrane is therefore vital for the function of the bio-solar cell. A liposomal model system based on liposomes formed by oleic acid was used to develop and study the incorporation of PEDOT-S to fatty acid membranes. The liposomes allow for a more controllable and easily manipulated system compared to the thylakoid membrane. In the model system, PEDOT-S could successfully be incorporated to the membrane, and the developed methods were applied to the real system of thylakoid membranes. We found that a bio-compatible electrolyte and ...http://www.diva-portal.org/smash/record.jsf?pid=diva2:648164
Comprehensive vaccine design for commensal disease progression | Science Advances
Proteins and polysaccharide components were colocalized through a liposomal delivery system. LEPS liposomal carriers were composed of DOPC/DOPG/DOGS-NTA-Ni/cholesterol/DSPE-PEG2000 at a molar ratio of 3:3:1:4:0.1 to a total lipid mass of 500 μg. After dissolving lipids in chloroform, the solution was sonicated for 1 min using a Branson 450D Sonifier (at 20% amplitude using a tapered tip) and then evaporated using a rotary evaporator to form a film. Lipids were then rehydrated with phosphate-buffered saline (PBS) containing the polysaccharide antigens to form liposomes, which were then passed 10 to 12 times through a handheld extruder (Avanti Polar Lipids) with a pore size of 200 nm. On ice, the background liposome solution was passed twice through a filter with 50-nm pore size and replaced each time with PBS. Next, proteins were incubated with liposomes for 30 min at 4°C with surface attachment mediated via polyhistidine tag-Ni chelation. CRM197 was included ...http://advances.sciencemag.org/content/3/10/e1701797.full
PEG altered the pharmacokinetic property of the DSPC/cholesterol liposomal doxorubicin by decreasing the Vss and clearance, and thereby increasing plasma AUC. These results are consistent with the notion that sterically stabilized liposome may reduce the RES uptake and enhance the longevity of liposomal doxorubicin in circulation, but above 3%, the gain in pharmacokinetic advantage was only slight. Compared with conventional liposomes, sterically stabilized liposomes have a 100-fold increase in AUC (3) . However, for the DSPC system used in this study, the AUC of liposomal doxorubicin with 6% PEG-modified lipid was only approximately twice that of liposomal doxorubicin without PEG, regardless of dosage or tumor-bearing status. Daunorubicin liposomes composed of DSPC/cholesterol without PEG also had a similar AUC (20) . The higher transition temperature and homogeneity in fatty acid of DSPC confers the higher stability to this ...http://clincancerres.aacrjournals.org/content/5/11/3645