MANY anti-cancer drugs are packaged for delivery into tiny fatty envelopes called liposomes.
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This fact, the two researchers hoped, might let them track where the liposomes are going.
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Because tumour cells are bound more loosely than healthy cells, liposomes squeeze between them more easily.
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Soon, researchers were using liposomes to smuggle DNA repair enzymes into the skin cells of human test subjects.
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In the three decades since, researchers have repeatedly demonstrated that liposomes can transport DNA repair enzymes into skin cells.
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Results were promising: Cells treated with Yarosh's enzyme-loaded liposomes removed more irradiated DNA, mended faster, and survived longer.
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Then he found a way to package it and other DNA-repair enzymes inside tiny spherical pockets of phospholipids called liposomes.
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So the company I founded is now a subsidiary of Estée Lauder, and it continues to supply these repair enzymes and liposomes.
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A way of discovering where the liposomes are going in a particular individual might permit treatments to be tailored to that patient's needs.
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On one end of the negotiating table sat Mr. Weissmann, the Princeton-educated son of a psychologist and a research scientist who is credited with codiscovering, and coining the term, liposomes.
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They injected mice that had metastatic breast cancer with their doped liposomes and were able, using a PET scanner, to follow what happened to the drugs therein over the course of a week.
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These liposomes may be digested while in the macrophage's phagosome, thus releasing its drug. Liposomes can also be decorated with opsonins and ligands to activate endocytosis in other cell types. The use of liposomes for transformation or transfection of DNA into a host cell is known as lipofection. In addition to gene and drug delivery applications, liposomes can be used as carriers for the delivery of dyes to textiles, pesticides to plants, enzymes and nutritional supplements to foods, and cosmetics to the skin.
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Non-viral methods involve complexing therapeutic DNA to various macromolecules including cationic lipids and liposomes, polymers, polyamines and polyethylenimine, and nanoparticles. FuGene 6 and modified cationic liposomes are two non-viral gene delivery methods that have so far been utilized for gene delivery to cartilage. FuGene 6 is a non-liposomal lipid formulation, which has proved to be successful in transfecting a variety of cell lines. Liposomes have shown to be an appropriate candidate for gene delivery, where cationic liposomes are made to facilitate the interaction with the cell membranes and nucleic acids.
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Cationic liposomes are structures that are made of positively charged lipids and are increasingly being researched for use in gene therapy due to their favorable interactions with negatively charged DNA and cell membranes. Upon interacting with negatively charged DNA, cationic liposomes form clusters of aggregated vesicles. At a critical density the DNA is condensed and becomes encapsulated within a lipid bilayer, although it is possible that the liposomes bind along the surface of the DNA, retaining its shape. They are also able to interact with negatively charged cell membranes more readily than classical liposomes.
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Targeted liposomes can target nearly any cell type in the body and deliver drugs that would otherwise be systemically delivered. Naturally toxic drugs can be much less systemically toxic if delivered only to diseased tissues. Polymersomes, morphologically related to liposomes, can also be used this way. Also morphologically related to liposomes are highly deformable vesicles, designed for non-invasive transdermal material delivery, known as transfersomes.
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Liposomes are sphere-shaped vesicular structures self-assembled in a solvent composed of a broad type of lipids or other amphiphilic molecules. The vesicle structure of liposomes improves the effects on drug penetration through biological membranes, which enhance transdermal drug delivery.
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DPPC is also used to form liposomes that are used as components of drug delivery systems.
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Liposomes as a carrier for mannophosphoinositide antigens of mycobacteria. Indian J. Biochem. Biophys. 30:160–165.
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Contacting koded liposomes with microplates or other surfaces can cause the labeling of the microplate surface.
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Liposomes are also used as outer shells of some microbubble contrast agents used in contrast-enhanced ultrasound.
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Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range, with various targeting ligands attached to their surface, allowing for their surface-attachment and accumulation in pathological areas for treatment of disease.Torchilin, VP “Multifunctional Nanocarriers.” Adv Drug Deliv Rev 2006 Dec; 58 (14): 1532-55 doi: 10.1016/j.addr.2006.09.
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For topical applications on skin, specialized lipids like phospholipids and sphingolipids may be used to make drug-free liposomes as moisturizers, and with drugs such as for anti-ultraviolet radiation applications. In biomedical research, unilamellar liposomes are extremely useful to study biological systems and mimicking cell functions. As a living cell is very complicated to study, unilamellar liposomes provide a simple tool to study membrane interaction events such as membrane fusion, protein localization in the plasma membrane, study ion channels, etc.
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A unilamellar liposome is a spherical chamber/vesicle, bounded by a single bilayer of an amphiphilic lipid or a mixture of such lipids, containing aqueous solution inside the chamber. Unilamellar liposomes are used to study biological systems and to mimic cell membranes, and are classified into three groups based on their size: small unilamellar liposomes/vesicles (SUVs) that with a size range of 20–100 nm, large unilamellar liposomes/vesicles (LUVs) with a size range of 100–1000 nm and giant unilamellar liposomes/vesicles (GUVs) with a size range of 1-200 µm. GUVs are mostly used as models for biological membranes in research work. Animal cells are 10–30 µm and plant cells are typically 10–100 µm.
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Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range with various targeting ligands attached to their surface allowing for their surface-attachment and accumulation in pathological areas for treatment of disease. Drug-loaded polymeric micelle formed from self-assembly of amphiphilic block copolymers in aqueous media. Drug-loaded polymeric micelles with various targeting functions.
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Scheme of a liposome formed by phospholipids in an aqueous solution. Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range with various targeting ligands attached to their surface allowing for their surface-attachment and accumulation in pathological areas for treatment of disease. A liposome is a spherical vesicle having at least one lipid bilayer.
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DOTAP is a cationic surfactant and is able to form stable cationic liposomes in solution, these readily absorb DNA and other negatively charged organic compounds. The DNA laden liposomes can then be added directly to cell culture medium, where they will combine with the cell membrane and release their payload into the cell.
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Vitamin C molecules can also be bound to the fatty acid palmitate, creating ascorbyl palmitate, or else incorporated into liposomes.
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To deliver the molecules to a site of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents; this is a complex and non-spontaneous event, however. By preparing liposomes in a solution of DNA or drugs (which would normally be unable to diffuse through the membrane) they can be (indiscriminately) delivered past the lipid bilayer, but are then typically distributed non-homogeneously. Liposomes are used as models for artificial cells. Liposomes can also be designed to deliver drugs in other ways.
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Further advances in liposome research have been able to allow liposomes to avoid detection by the body's immune system, specifically, the cells of reticuloendothelial system (RES). These liposomes are known as "stealth liposomes". They were first proposed by G. Cevc and G. Blume and, independently and soon thereafter, the groups of L. Huang and V. Torchilin and are constructed with PEG (Polyethylene Glycol) studding the outside of the membrane. The PEG coating, which is inert in the body, allows for longer circulatory life for the drug delivery mechanism.
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Options identified thus far for use combined with a malaria vaccine include mycobacterial cell walls, liposomes, monophosphoryl lipid A and squalene.
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Much of the current research involving liposomes is focused on improving the delivery of anticancer drugs such as doxorubicin and paclitaxel.
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Polymersomes are similar to liposomes, which are vesicles formed from naturally occurring lipids. While having many of the properties of natural liposomes, polymersomes exhibit increased stability and reduced permeability. Furthermore, the use of synthetic polymers enables designers to manipulate the characteristics of the membrane and thus control permeability, release rates, stability and other properties of the polymersome.
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However, research currently seeks to investigate at what amount of PEG coating the PEG actually hinders binding of the liposome to the delivery site. Studies have also shown that PEGylated liposomes elicit anti-IgM antibodies, thus leading to an enhanced blood clearance of the liposomes upon re-injection. In addition to a PEG coating, most stealth liposomes also have some sort of biological species attached as a ligand to the liposome, to enable binding via a specific expression on the targeted drug delivery site. These targeting ligands could be monoclonal antibodies (making an immunoliposome), vitamins, or specific antigens, but must be accessible.
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Immunoliposomes are antibody-conjugated liposomes. Liposomes can carry drugs or therapeutic nucleotides and when conjugated with monoclonal antibodies, may be directed against malignant cells. Immunoliposomes have been successfully used in vivo to convey tumour- suppressing genes into tumours, using an antibody fragment against the human transferrin receptor. Tissue-specific gene delivery using immunoliposomes has been achieved in brain and breast cancer tissue.
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The liposome can be used as a vehicle for administration of nutrients and pharmaceutical drugs.Kimball's Biology Pages, "Cell Membranes." Liposomes can be prepared by disrupting biological membranes (such as by sonication). Liposomes are most often composed of phospholipids, especially phosphatidylcholine, but may also include other lipids, such as egg phosphatidylethanolamine, so long as they are compatible with lipid bilayer structure.
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Recently, liposomes have also been successfully used for delivery of small peptides and this technique is an alternative to delivery with oily emulsion adjuvants.
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Scheme of a liposome formed by phospholipids in an aqueous solution Mifamurtide is muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic analogue of muramyl dipeptide. The side chains of the molecule give it a longer elimination half-life than the natural substance. The substance is applied encapsulated into liposomes (L-MTP-PE). Being a phospholipid, it accumulates in the lipid bilayer of the liposomes in the infusion.
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Lipoplexes can also be formed from cationic liposomes and DNA solutions, to yield transfection agents. Cationic liposomes cross the BBB through adsorption mediated endocytosis followed by internalization in the endosomes of the endothelial cells. By transfection of endothelial cells through the use of lipoplexes, physical alterations in the cells could be made. These physical changes could potentially improve how some nanoparticle drug-carriers cross the BBB.
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Phospholipid liposomes are used as targeted drug delivery systems. Hydrophilic drugs can be carried as solution inside the SUVs or MLVs and hydrophobic drugs can be incorporated into lipid bilayer of these liposomes. If injected into circulation of human/animal body, MLVs are preferentially taken up phagocytic cells, and thus drugs can be targeted to these cells. For general or overall delivery, SUVs may be used.
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Until recently the clinical uses of liposomes were for targeted drug delivery, but new applications for the oral delivery of certain dietary and nutritional supplements are in development. This new application of liposomes is in part due to the low absorption and bioavailability rates of traditional oral dietary and nutritional tablets and capsules. The low oral bioavailability and absorption of many nutrients is clinically well documented. Therefore, the natural encapsulation of lypophilic and hydrophilic nutrients within liposomes would be an effective method of bypassing the destructive elements of the gastric system allowing the encapsulated nutrient to be efficiently delivered to the cells and tissues.
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It is important to note that certain factors have far-reaching effects on the percentage of liposome that are yielded in manufacturing, as well as the actual amount of realized liposome entrapment and the actual quality and long-term stability of the liposomes themselves. They are the following: (1) The actual manufacturing method and preparation of the liposomes themselves; (2) The constitution, quality, and type of raw phospholipid used in the formulation and manufacturing of the liposomes; (3) The ability to create homogeneous liposome particle sizes that are stable and hold their encapsulated payload. These are the primary elements in developing effective liposome carriers for use in dietary and nutritional supplements.
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Liposomes that contain low (or high) pH can be constructed such that dissolved aqueous drugs will be charged in solution (i.e., the pH is outside the drug's pI range). As the pH naturally neutralizes within the liposome (protons can pass through some membranes), the drug will also be neutralized, allowing it to freely pass through a membrane. These liposomes work to deliver drug by diffusion rather than by direct cell fusion.
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A similar approach can be exploited in the biodetoxification of drugs by injecting empty liposomes with a transmembrane pH gradient. In this case the vesicles act as sinks to scavenge the drug in the blood circulation and prevent its toxic effect. Another strategy for liposome drug delivery is to target endocytosis events. Liposomes can be made in a particular size range that makes them viable targets for natural macrophage phagocytosis.
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Commercially available FAM is a mixture of two isomers, 5-FAM and 6-FAM, and the correct name is 5(6)-carboxyfluorescein. The dyes are membrane-impermeant and can be loaded into cells by microinjection or scrape loading. It can be incorporated into liposomes, and allows for the tracking of liposomes as they pass through the body. In addition, carboxyfluorescein has been used to track division of cells.
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Cord factor beads are easily created and applied to organisms for study, and then easily recovered. It is possible to form cord factor liposomes through water emulsion; these liposomes are nontoxic and can be used to maintain a steady supply of activated macrophages. Cord factor under proper control can potentially be useful in fighting cancer because IL-12 and IFN-γ are able to limit the growth of tumors.
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009 The most common vehicle currently used for targeted drug delivery is the liposome. Liposomes are non-toxic, non-hemolytic, and non-immunogenic even upon repeated injections; they are biocompatible and biodegradable and can be designed to avoid clearance mechanisms (reticuloendothelial system (RES), renal clearance, chemical or enzymatic inactivation, etc.) Lipid-based, ligand-coated nanocarriers can store their payload in the hydrophobic shell or the hydrophilic interior depending on the nature of the drug/contrast agent being carried. The only problem to using liposomes in vivo is their immediate uptake and clearance by the RES system and their relatively low stability in vitro. To combat this, polyethylene glycol (PEG) can be added to the surface of the liposomes.
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Microvesicular steatosis is characterized by small intracytoplasmic fat vacuoles (liposomes) which accumulate in the cell. Common causes are tetracyclines, acute fatty liver of pregnancy, Reye's syndrome, and hepatitis C.
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Though the genus Picrophilus is not known to be involved in AMD, its extreme acidophily is of interest, for instance its proton-resistant liposomes, which could be present in AMD acidophiles.
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The second possibility can be realized by inducing attractive interactions between the DNA segments by multivalent cationic charged ligands (multivalent metal ions, inorganic cations, polyamines, protamines, peptides, lipids, liposomes and proteins).
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Contrary to the synoviocytes which are dividing cells and can be efficacy transduced in vivo using either liposomes or viral vectors, in vivo delivery of genes to chondrocytes is hindered by the dense extra cellular matrix that surrounds these cells. Chondrocytes are non- dividing cells, embedded in a network of collagens and proteoglycans; however researches suggest that genes can be transferred to chondrocytes within normal cartilage by intraarticular injection of liposomes containing sendai virus (HVJ- liposomes) and adeno- associated virus. Most efficient methods of gene transfer to cartilage have involved ex vivo strategies using chondrocytes or chondroprogenitor cells. Chondrocytes are genetically enhanced by transferring complementary DNA encoding IL-1RA, IGF-1, or matrix break down inhibitors mentioned in Table 1.
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Low shear rates create multilamellar liposomes. The original aggregates, which have many layers like an onion, thereby form progressively smaller and finally unilamellar liposomes (which are often unstable, owing to their small size and the sonication-created defects). Sonication is generally considered a "gross" method of preparation as it can damage the structure of the drug to be encapsulated. Newer methods such as extrusion, micromixing and Mozafari method are employed to produce materials for human use.
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Certain anticancer drugs such as doxorubicin (Doxil) and daunorubicin may be administered via liposomes. Liposomal cisplatin has received orphan drug designation for pancreatic cancer from EMEA. A study published in May 2018 also explored the potential use of liposomes as "nano- carriers" of fertilizing nutrients to treat malnourished or sickly plants. Results showed that these synthetic particles "soak into plant leaves more easily than naked nutrients," further validating the utilization of nanotechnology to increase crop yields.
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The first stealth liposomes were passively targeted at tumor tissues. Because tumors induce rapid and uncontrolled angiogenesis they are especially “leaky” and allow liposomes to exit the bloodstream at a much higher rate than normal tissue would. More recently work has been undertaken to graft antibodies or other molecular markers onto the liposome surface in the hope of actively binding them to a specific cell or tissue type. Some examples of this approach are already in clinical trials.
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Kodesomes are liposomes that have been decorated with FSL Kode constructs. These have been used to deposit FSL constructs onto microplates to create diagnostic assays. They also have the potential for therapeutic use.
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Poly- or oligotuftsin derivatives can be used as delivery systems. For example, a 35-40 unit repeat was used as a carrier for the preparation of synthetic immunogens in malaria vaccines against Plasmodium falciparum.Siemion, I. Z. & Kluczyk, A. Tuftsin: On the 30-year anniversary of Victor Najjar’s discovery. Peptides 20, 645–674 (1999) Tuftsin enhances the action of rifampicin-bearing liposomes in the treatment of tuberculosis, and that amphotericin B-bearing liposomes in the treatment of human aspergillosis in mice.
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Liposomes are composed of vesicular bilayers, lamellae, made of biocompatible and biodegradable lipids such as sphingomyelin, phosphatidylcholine, and glycerophospholipids. Cholesterol, a type of lipid, is also often incorporated in the lipid-nanoparticle formulation. Cholesterol can increase stability of a liposome and prevent leakage of a bilayer because its hydroxyl group can interact with the polar heads of the bilayer phospholipids. Liposomes have the potential to protect the drug from degradation, target sites for action, and reduce toxicity and adverse effects.
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Liposomes are structures which consist of at least one lipid bilayer surrounding an aqueous core. This hydrophobic/hydrophilic composition is particularly useful for drug delivery as these carriers can accommodate a number of drugs of varying lipophilicity. Disadvantages associated with using liposomes as drug carriers involve poor control over drug release. Drugs which have high membrane- permeability can readily 'leak' from the carrier, while optimization of in vivo stability can cause drug release by diffusion to be a slow and inefficient process.
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Various vectors have been developed to carry the therapeutic genes to cells. There are two broad categories of gene delivery vectors: Viral vectors, involving viruses and non- viral agents, such as polymers and liposomes.
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Nardin, C; Hirt, T; Leukel, J; Meier, W Langmuir, 16, 1035-1041 In general they can be prepared by the methods used in the preparation of liposomes. Film rehydration, direct injection method or dissolution method.
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This TEM-appearance became famous as Robertson's unit membrane - the basis of all biological membranes, and structure of lipid bilayer in unilamellar liposomes. In multilamellar liposomes, many such lipid bilayer sheets are layered concentrically with water layers in between. Figure 1 Multi-lamellar phase of aqueous lipid dispersions, each white lamella represents a lipid bilayer organization in liposome made by vortex-mixing of dried total lipid extract of spinach thylakoid membranes with distilled water. Phosphotungstic acid negative stained sample viewed with transmission electron microscopy technique.
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Example of lipid polymorphism as bilayer (le), reverse spherical micelles (M) and reverse hexagonal cylinders H-II phase (H) in negatively stained transmission electron micrograph of spinach thylakoid lipid-water dispersions. Mixed lipid liposomes can undergo changes into different phase dispersion structures, called lipid polymorphisms, for example, spherical micelles, lipid bilayer lamellae and hexagonal phase cylinders, depending on physical and chemical changes in their microenvironment. Phase transition temperature of liposomes and biological membranes can be measured using calorimetry, magnetic resonance spectroscopy and other techniques.
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To date, the most successful commercial application of lipid bilayers has been the use of liposomes for drug delivery, especially for cancer treatment. (Note- the term “liposome” is in essence synonymous with “vesicle” except that vesicle is a general term for the structure whereas liposome refers to only artificial not natural vesicles) The basic idea of liposomal drug delivery is that the drug is encapsulated in solution inside the liposome then injected into the patient. These drug-loaded liposomes travel through the system until they bind at the target site and rupture, releasing the drug. In theory, liposomes should make an ideal drug delivery system since they can isolate nearly any hydrophilic drug, can be grafted with molecules to target specific tissues and can be relatively non- toxic since the body possesses biochemical pathways for degrading lipids.
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DPPC is usually used for research purposes, such as creating liposomes and bilayers which are involved in bigger studies. The Langmuir–Blodgett technique allows the synthesis of liposomal DPPC bilayers. Currently, these liposomes are used in the study of the properties of this phosphatidylcholine and of its use as a mechanism of drug delivery in the human body. Furthermore, because vesicle fusion dynamics are different for lipids in the gel phase versus the fluid phase, it allows scientists to use DPPC along with DOPC in Atomic Force Microscopy and Atomic Force Spectroscopy.
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The presence of unsaturated bonds (double bonds) in lipids for example, creates a kink in acyl chains which further changes the lipid packing and results in a looser packing. Therefore, the composition and sizes of the unilamellar liposomes must be chosen carefully based on the subject of the study. Each lipid bilayer structure is comparable to lamellar phase lipid organization in biological membranes, in general. In contrast, multilamellar liposomes (MLVs), consist of many concentric amphiphilic lipid bilayers analogous to onion layers, and MLVs may be of variable sizes up to several micrometers.
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It has been suggested that double-walled "bubbles" of lipids like those that form the external membranes of cells may have been an essential first step. Experiments that simulated the conditions of the early Earth have reported the formation of lipids, and these can spontaneously form liposomes, double-walled "bubbles," and then reproduce themselves. Although they are not intrinsically information-carriers as nucleic acids are, they would be subject to natural selection for longevity and reproduction. Nucleic acids such as RNA might then have formed more easily within the liposomes than they would have outside.
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Alec Douglas Bangham FRS (10 November 1921 Manchester – 9 March 2010 Great Shelford) was a British biophysicist who first studied blood clotting mechanisms but became well known for his research on liposomes and his invention of clinically useful artificial lung surfactants.
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In this technique, drug particles are enveloped in a plasma membrane-bound vesicle. Folate is attached to polyethylene glycol bound to the phosphate heads of membrane phospholipids, thus directing the liposomes to FRs of tumor cells, by which they are engulfed.
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Following her PhD training, Auguste began her postdoctoral fellowship at the Massachusetts Institute of Technology, working under the mentorship of Robert Langer. She worked in the Department of Chemical Engineering optimizing liposomal drug delivery methods to deliver short interfering RNA (siRNA) to mediate gene knockdown. She built the liposomes based on her previous work using pH- dependent liposomes with the PEG coating to prevent immune opsonization, but with the added ability to deliver siRNA to the endosome of the cell. Auguste also helped to co-author the Third Edition of the Principals of Tissue Engineering Textbook.
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Lipid vesicles or liposomes are approximately spherical pockets that are enclosed by a lipid bilayer. These structures are used in laboratories to study the effects of chemicals in cells by delivering these chemicals directly to the cell, as well as getting more insight into cell membrane permeability. Lipid vesicles and liposomes are formed by first suspending a lipid in an aqueous solution then agitating the mixture through sonication, resulting in a vesicle. By measuring the rate of efflux from that of the inside of the vesicle to the ambient solution, allows researcher to better understand membrane permeability.
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Debi Prasad Sarkar, born on 15 January 1958, graduated (honours) in chemistry in 1978 and obtained a master's degree in biochemistry in 1980, both from Banaras Hindu University. His career started as a research assistant at the University of Delhi in 1985, working on Liposomes as immunomodulators and drug delivery using Liposomes and he secured a PhD degree for his thesis, Immunogenicity of carbohydrate determinants mediated through Liposomes: Liposome-mediated drug delivery from the University of Delhi in 1986. His post-doctoral studies were at the National Cancer Institute of the National Institutes of Health where he spent two years (1986–88) as visiting fellow and returned to Delhi University to take up the position of a lecturer of biochemistry. He stayed at the university for the rest of his academic career, holding various positions as the senior lecturer (1993–96) and reader (1996–2008), to superannuate as a professor in 2023.
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These diseases result from an accumulation of specific substrates, due to the inability to break them down. These genetic defects are related to several neurodegenerative disorders, cancers, cardiovascular diseases, and aging-related diseases. Lysosomes should not be confused with liposomes, or with micelles.
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A vesosome is a multi-compartmental structure of lipidic nature used to deliver drugs. They can be considered multivesicular vesicles (MVV)Daniels, Rolf. - Liposomes - Classification, Processing Technologies, Industry Applications and Risk Assessment Retrieved 25 November 2012 and are, therefore, liposome derived structures.
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They are structurally similar to liposomes in having a bilayer, however, the materials used to prepare niosomes make them more stable. It can entrap both hydrophilic and lipophilic drugs, either in an aqueous layer or in a vesicular membrane made of lipid material.
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Although radium does not easily form stable molecular complexes, there has been presented data on methods to increase and customize its specificity for particular cancers by linking it to monoclonal antibodies, by enclosing the 223Ra in liposomes bearing the antibodies on their surface.
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FSL Kode constructs with all these aforementioned features are also known as Kode Constructs. The process of modifying surfaces with FSL Kode constructs is known as "koding" and the resultant "koded" cells, viruses and liposomes are respectively known as kodecytes, and kodevirions.
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A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers. Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.
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She worked on creating hydrophobically-modified polyethylene glycol (PEG) polymers that can evade complement binding, an immune molecule that tags pathogens for immune system clearance and destruction. After completing her Master’s in 2004, Auguste further optimized the design of drug delivery liposomes with PEG protective layers so that they could be enabled to lose their protective layer once inside the cell to fuse with the endosome and release contents into the cell. She was able to design liposomes that conjugate PEG and maintain them at pH levels similar to blood, and then dissociate them once they arrive at pH levels below 7.4. Auguste completed her PhD in 2005.
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Their integrity as a closed, bilayer structure, that could release its contents after detergent treatment (structure-linked latency) was established by Bangham, Standish and Weissmann in the next year. Weissmann - during a Cambridge pub discussion with Bangham - first named the structures "liposomes" after the lysosome, which his laboratory had been studying: a simple organelle the structure-linked latency of which could be disrupted by detergents and streptolysins. Liposomes can be easily distinguished from micelles and hexagonal lipid phases by negative staining transmission electron microscopy. Alec Douglas Bangham with colleagues Jeff Watkins and Malcolm Standish wrote the 1965 paper that effectively launched the liposome “industry”.
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Diagram of liposome showing a phospholipid bilayer surrounding an aqueous interior. One type of nanoparticle involves use of liposomes as drug molecule carriers. The diagram on the right shows a standard liposome. It has a phospholipid bilayer separating the interior from the exterior of the cell.
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There are different types of drug delivery vehicles, such as polymeric micelles, liposomes, lipoprotein-based drug carriers, nano- particle drug carriers, dendrimers, etc. An ideal drug delivery vehicle must be non-toxic, biocompatible, non-immunogenic, biodegradable, and must avoid recognition by the host's defense mechanisms[3].
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The detergent effect draws on surfactin's ability to insert its fatty acid chain into the bilipidic layer causing disorganization leading to membrane permeability.Kragh-Hansen, U, M Maire, and J Moller. The Mechanism of Detergent Solubilization of Liposomes and Protein-Containing Membranes. Biophys. J. (1998) 75: 2932–2946.
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As of 2016, there is no evidence for chrysin being used in human clinical applications. Research showed that orally administered chrysin does not have clinical activity as an aromatase inhibitor. Nanoformulations of polyphenols, including chrysin, are made using various carrier methods, such as liposomes and nanocapsules.
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Dayan, N., Touitou, E. (2000) Carriers for Skin Delivery of Trihexyphenidyl HCl: Ethosomes vs. Liposomes. Biomaterials, 21:1879-1885.Touitou, E., Dayan, N., Bergelson, L., Godin, B., Eliaz, M. (2000) Ethosomes-Novel Vesicular Carriers for Enhanced Delivery: Characterization and Skin Penetration Properties, J. Control. Release, 65:403-418.
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It works in part by interfering with the function of DNA. Doxorubicin was approved for medical use in the United States in 1974. It is on the World Health Organization's List of Essential Medicines. Versions that are pegylated and in liposomes are also available; however, are more expensive.
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In lamellar lipid bilayers, polar headgroups of lipids align together at the interface of water and hydrophobic fatty-acid acyl chains align parallel to one another 'hiding away' from water. The lipid head groups are somewhat more 'tightly' packed than relatively 'fluid' hydrocarbon fatty acyl long chains. The lamellar lipid bilayer organization, thus reveals a 'flexibility gradient' of increasing freedom of motions from near the head- groups towards the terminal fatty-acyl chain methyl groups. Existence of such a dynamic organization of lamellar phase in liposomes as well as biological membranes can be confirmed by spin label electron paramagnetic resonance and high resolution nuclear magnetic resonance spectroscopy studies of biological membranes and liposomes.
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ENPP7 may also affect cholesterol absorption. In the intestinal tract cholesterol and sphingomyelin are co-exiting in plasma membrane and in lipid vesicles, liposomes and micelles. The two molecules form a stable complex via van der Waals forces. Cholesterol absorption can be inhibited by supplementation of sphingomyelin in the diet.
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Because of its tetraether lipid material, the membrane of extreme thermophilic Archaea is unique in its composition. Archaea lipids are a promising source of liposomes with exceptional stability of temperature and pH and tightness against leakage of solute. Such archaeosomes are possible instruments for the delivery of medicines, vaccines, and genes.
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When injected into the body, synthetic nanosponges made of liposomes can be coated with leukocytes. These leukocytes can be incorporated in nanoparticles though methods known as the "ghost-cell" or "hitchhiking" strategy. Hitchhiking strategy is when nanoparticles are trafficked by living leukocytes. The ghost cell method entails nanoparticles coated in the natural membrane.
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However, some natural occurring polymers such as chitosan, gelatin, sodium alginate, and albumin are used in some drug delivering nanocapsules. Other nanocapsule shells include liposomes, along with polysaccharides and saccharides. Polysaccharides and saccharides are used due to their non-toxicity and biodegradability. They are attractive to use as they resemble biological membranes.
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Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breathing and prevents alveolar collapse during breathing. It also plays an important role in the study of liposomes and human bilayers.
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These polymers may be administered in the liquid form through a macroscopic injection and solidify or gel in situ because of the difference in pH or temperature. Nanoparticle and liposome preparations are also routinely used for material encapsulation and delivery. A major advantage of liposomes is their ability to fuse to cell and organelle membranes.
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Identification of lamellar(le), reverse- miceller(M) and reverse-hexagonal H-II cylinders(H) lipid phases by negative staining. Negative staining transmission electron microscopy has also been successfully employed for study and identification of aqueous lipid aggregates like lamellar liposomes (le), inverted spherical micelles (M) and inverted hexagonal HII cylindrical (H) phases (see figure).
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MBs can serve as drug delivery vehicles in a variety of methods. The most notable of these include: (1) incorporating a lipophilic drug to the lipid monolayer, (2) attaching nanoparticles and liposomes to the microbubble surface, (3) enveloping the microbubble within a larger liposome, and (4) electrostatically bonding nucleic acids to the MB surface.
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Nanocarriers discovered thus far include polymer conjugates, polymeric nanoparticles, lipid-based carriers, dendrimers, carbon nanotubes, and gold nanoparticles. Lipid-based carriers include both liposomes and micelles. Examples of gold nanoparticles are gold nanoshells and nanocages. Different types of nanomaterial being used in nanocarriers allows for hydrophobic and hydrophilic drugs to be delivered throughout the body.
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There are several methods to prepare unilamellar liposomes and the protocols differ based on the type of desired unilamellar vesicles. Different lipids can be bought either dissolved in chloroform or as lyophilized lipids. In the case of lyophilized lipids, they can be solubilized in chloroform. Lipids are then mixed with a desired molar ratio.
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This channel probably delivers the N-terminal adenylate cyclase to the host cell cytoplasm. Mutations in residues in an amphipathic α-helix (Glu509 and Glu516) in the pore-forming domain block adenylate cyclase translocation and modulate cation selectivity of the membrane channel. ACT does not use a protein receptor and inserts into liposomes. Phosphatidylethanolamine and cholesterol stimulate ACT insertion.
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Depending on the haptens being used, other factors in considering the carrier proteins could include their in vivo toxicity, commercial availability and cost. The most common carriers include serum globulin, albumins, ovalbumin and many others. Although proteins are mostly employed for hapten conjugation, synthetic polypeptides such as Poly-L-glutamic acid, polysaccharides and liposomes could also be used.
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Then chloroform is evaporated using a gentle stream of nitrogen (to avoid oxygen contact and oxidation of lipids) at room temperature. A rotary evaporator can be used to form a homogeneous layer of liposomes. This step removes the bulk of chloroform. To remove the residues of trapped chloroform, lipids are placed under vacuum from several hours to overnight.
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Decontamination: Prolidase from the hyperthermophilic archaeon Pyrococcus furiosus (Pfprol) shows potential for application in decontamination of organophosphorus nerve agents in chemical warfare agents. Additionally, prolidase could also serve to detect fluorine- containing organophosphorus neurotoxins, like the G-type chemical warfare agents, and could antagonize organophosphorous intoxication and protect against the effects of diisopropylfluorophosphate when encapsulated in liposomes.
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Additionally, when present in vivo with serum lipids FSLs will elute from the membrane into the plasma at a rate of about 1% per hour. In fixed cells or inactive cells (e.g. red cells) stored in serum free media the constructs are retained normally. Liposomes are easy koded by simply adding FSL Kode constructs into the preparation.
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Electroporation, which involves pulsing electricity through cells to create holes in the membrane through which DNA can enter, has obvious cytotoxic effects and is not appropriate for in vivo applications. On the other hand, microinjection, the use of fine needles to physically inject genetic material into the cell nucleus, offers more control but is a high- skill, meticulous task in which a relatively low number of cells can be transfected. Although viral vectors can offer highly specific, high-efficiency transfection, the generation of such viruses is costly and time-consuming; furthermore, the inherent viral nature of the gene transfer often triggers an immune response, thus limiting in vivo applications. In fact, many modern transfection technologies are based on artificially assembled liposomes (both liposomes and PAMAMs are positively charged macromolecules).
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It is usually available from sources such as egg yolk, marine sources, soybeans, milk, rapeseed, cottonseed, and sunflower oil. It has low solubility in water, but is an excellent emulsifier. In aqueous solution, its phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration and temperature. This results in a type of surfactant that usually is classified as amphipathic.
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One such development is in the delivery of doxorubicin. While it is an effective inducer of apoptosis, doxorubicin is quickly filtered out of the body. By loading a PEG-liposome with doxorubicin the circulation time and localization to tumors greatly increases. Cancerous tumors characteristically have extensive angiogenesis and leaky vasculatures, which causes the PEG-liposomes to naturally accumulate in the tumor.
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Another mechanism is adsorption mediated transcytosis, where electrostatic interactions are involved in mediating nanoparticle crossing of the BBB. Cationic nanoparticles (including cationic liposomes) are of interest for this mechanism, because their positive charges assist binding on the brain's endothelial cells. Using TAT-peptides, a cell-penetrating peptide, to functionalize the surface of cationic nanoparticles can further improve drug transport into the brain.
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Further, functionalizing the surface of solid lipid nanoparticles with polyethylene glycol (PEG) can result in increased BBB permeability. Different colloidal carriers such as liposomes, polymeric nanoparticles, and emulsions have reduced stability, shelf life and encapsulation efficacy. Solid lipid nanoparticles are designed to overcome these shortcomings and have an excellent drug release and physical stability apart from targeted delivery of drugs.
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Nanocarrier vehicles (~20–200 nm in diameter) can transport drugs and other therapeutic molecules. These therapies can be targeted to selectively extravasate through tumor vasculature via the EPR effect. Nanocarriers are now considered the gold standard of targeted cancer therapy because it can target tumors that are hypovascularized, such as prostate and pancreatic tumors. These efforts include protein capsids and liposomes.
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S-layer proteins have the natural capability to self-assemble into regular monomolecular arrays in solution and at interfaces, such as solid supports, the air-water interface, lipid films, liposomes, emulsomes, nanocapsules, nanoparticles or micro beads. S-layer crystal growth follows a non-classical pathway in which a final refolding step of the S-layer protein is part of the lattice formation.
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The choice of liposome preparation method depends, i.a., on the following parameters: # the physicochemical characteristics of the material to be entrapped and those of the liposomal ingredients; # the nature of the medium in which the lipid vesicles are dispersed # the effective concentration of the entrapped substance and its potential toxicity; # additional processes involved during application/delivery of the vesicles; # optimum size, polydispersity and shelf-life of the vesicles for the intended application; and, # batch-to-batch reproducibility and possibility of large- scale production of safe and efficient liposomal products Useful liposomes rarely form spontaneously. They typically form after supplying enough energy to a dispersion of (phospho)lipids in a polar solvent, such as water, to break down multilamellar aggregates into oligo- or unilamellar bilayer vesicles. Liposomes can hence be created by sonicating a dispersion of amphipatic lipids, such as phospholipids, in water.
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As such, nanoparticles, liposomes, polymersomes, microcapsules and a number of other particles have qualified as artificial cells. Micro-encapsulation allows for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it. The main advantages of encapsulation include improved mimicry in the body, increased solubility of the cargo and decreased immune responses. Notably, artificial cells have been clinically successful in hemoperfusion.
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Stryer et al., pp. 333–334. This is known as the hydrophobic effect. In an aqueous system, the polar heads of lipids align towards the polar, aqueous environment, while the hydrophobic tails minimize their contact with water and tend to cluster together, forming a vesicle; depending on the concentration of the lipid, this biophysical interaction may result in the formation of micelles, liposomes, or lipid bilayers.
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For example, enzyme action can be explained in terms of the shape of a pocket in the protein molecule that matches the shape of the substrate molecule or its modification due to binding of a metal ion. Similarly the structure and function of the biomembranes may be understood through the study of model supramolecular structures as liposomes or phospholipid vesicles of different compositions and sizes.
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In this technique siRNA first must be designed against the target gene. Once the siRNA is configured against the gene it has to be effectively delivered through a transfection protocol. Delivery is usually done by cationic liposomes, polymer nanoparticles, and lipid conjugation. This method is advantageous because it can deliver siRNA to most types of cells, has high efficiency and reproducibility, and is offered commercially.
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The following types of liposomes are visible: small monolamellar vesicles, large monolamellar vesicles, multilamellar vesicles, oligolamellar vesicles. A liposome has an aqueous solution core surrounded by a hydrophobic membrane, in the form of a lipid bilayer; hydrophilic solutes dissolved in the core cannot readily pass through the bilayer. Hydrophobic chemicals associate with the bilayer. A liposome can be hence loaded with hydrophobic and/or hydrophilic molecules.
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SOAT1 is an obligatory enzyme for cellular cholesterol storage and detoxification. For SQS, an enzyme controlling the committing step in cholesterol biosynthesis, the EMC has been shown to be sufficient for its integration into liposomes in vitro. Depletion of EMC6 and additional EMC proteins reduces the cell surface expression of the nicotinic Acetylcholine receptors in C. elegans. Knockdown of EMC2 has been observed to correlate with decreased CFTRΔF508 levels.
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Magnetic resonance imaging requires the use of nano-particles(liposomes) and an MRI contrast agent called gadolinium. The particles were then placed in vesicles via a polycarbonate membrane filter. The nano-particles are injected into the metastases evolved mice, and left there for twenty-four hours. These mice are then scanned, and in the imaging software there are accumulations of these particles in certain areas where cells have metastasized.
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Simple Diagram showing surfactant's function in stopping the collapse of the alveoli when exhaling DPPC is an amphipathic lipid. This characteristic is due to its hydrophilic head, composed of the polar phosphatidylcholine group, and its hydrophobic tails, formed by two nonpolar palmitic acid (C16) chains. This trait allows DPPC to easily and spontaneously form micelles, monolayers, bilayers and liposomes when it is in contact with a polar solvent.
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Archaerhodopsins are active transporters, using the energy from sunlight to pump H+ ions out of the cell to generate a proton motive force that is used for ATP synthesis. Removal of the retinal cofactor (e.g. by treatment with hydroxylamine) abolishes the transporter function and dramatically alters the absorption spectra of the proteins. The proton pumping ability of AR3 has been demonstrated in recombinant E. coli cells and of AR4 in liposomes.
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In pharmacology and medicine vectorization of drugs refers to (intracellular) targeting with plastic, noble metal or silicon nanoparticles or liposomes to which pharmacologically active substances are reversibly bound or attached by adsorption. CNRS researchers have devised a way to overcome the problem of multidrug resistance using polyalkylcyanoacrylate (PACA) nanoparticles as "vectors". Drug nanocarriers are expected to play a major role in delivering multiple drugs to tumor tissues by overcoming biological barriers.
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Another type of lipid- nanoparticle that can be used for drug delivery to the brain is a cationic liposome. These are lipid molecules that are positively charged. One example of cationic liposomes uses bolaamphiphiles, which contain hydrophilic groups surrounding a hydrophobic chain to strengthen the boundary of the nano-vesicle containing the drug. Bolaamphiphile nano-vesicles can cross the BBB, and they allow controlled release of the drug to target sites.
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Blocks of similar length form layers (often called lamellae in the technical literature). Between the cylindrical and lamellar phase is the gyroid phase. The nanoscale structures created from block copolymers could potentially be used for creating devices for use in computer memory, nanoscale-templating and nanoscale separations. Block copolymers are sometimes used as a replacement for phospholipids in model lipid bilayers and liposomes for their superior stability and tunability.
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Sulfolobus metallicus could be used for mass-producing archeal phospholipids. These lipids have promising applications in drug delivery by acting as liposomes, or they can be used as lubricants but can be expensive to synthesize. Sulfolobus metallicus can potentially be used to provide a cheaper way to synthesize these lipids. If Sulfolobus metallicus is used as a bioleacher on the industrial scale, it grows in volume in tons per day.
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Franz undertook research in many areas during his time at Monsanto. Some of his other chemistry research includes antiauxin chemistry (isothiazoles, isoxazoles, pyrazoles), plant chemistry, cell membrane chemistry (glyceride and phospholipid syntheses, liposomes), plant hormone chemistry (abscissic acid analogs, ethylene generators), and nitride sulfide chemistry. He also performed research pertaining to reaction mechanisms, coenzyme A antimetabolites, biorational design of herbicides, and periselective addition reactions of one- and threedipoles, as well as fundamental organic research.
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When inserted into liposomes and synthetic bilayers at low concentrations (2 nM), it provokes a cation-selective ion current with large unitary conductance. Chloride is not transported. It has been hypothesized that such channels could allow nutrient release and/or delivery of virulence factors during bacterial colonization of host plants. The leucine-zipper-like motifs may take part in the formation of oligomeric aggregates, and oligomerization could be related to HR elicitation.
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Active targeting uses biological molecules (antibodies, proteins, DNA and receptor ligands) to preferentially target the nanoparticles to the tumor cells. There are many types of nanoparticle delivery systems, such as silica, polymers, liposomes and magnetic particles. Nanoparticles made of magnetic material can also be used to concentrate agents at tumor sites using an externally applied magnetic field. They have emerged as a useful vehicle in magnetic drug delivery for poorly soluble agents such as paclitaxel.
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Schematic drawing of the steps followed during vesosome synthesis. Vesosome multicompartment structure encapsulates unilamellar liposomes within a second bilayer. For this purpose, it is necessary to form bilayers that can be opened and closed at will, without disrupting the inner content. This is achieved by adding ethanol to a variety of saturated phospholipids in the gel phase, which drives interdigitation of phospholipids bilayers and subsequent fusion of small vesicles to form flat bilayer sheets.
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He is one of the few researchers to work on use of Curcumin, a molecule obtained form food spice Turmeric, for preparing metallic nanoparticles using green synthetic routes to tune nanoparticle shape/size and towards various sensing applications. His research also modifies curcumin using nanotechnology for selective sensing and to improve its delivery and biomedical applications. His research first time showed that curcumin can be applied a membrane fluorescence probe to study liposomes properties.
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Scheme of a liposome formed by phospholipids in an aqueous solution. In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis) and transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes (not to be confused with lysosomes).
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Only the cells incubated with the gold nanoshells conjugated with the specific antibody (anti-HER2) were damaged by the laser. Another category of gold nanoshells are gold layer on liposomes, as soft template. In this case, drug can also be encapsulated inside and/or in bilayer and the release can be triggered by laser light. Gold is often used because it is a good absorber of light energy, it is tunable, non-biodegradable, and has imaging properties.
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Like the LM20, but with a high- sensitivity camera like that of the NS500, the NS200 has a housing and is ideal for use in industrial settings, such as manufacture of inks, paints, pigments, petrochemicals, and vaccines. Its configuration is designed for study of small or otherwise weakly scattering nanoparticles, such as viruses, phage, liposomes and other drug delivery nanoparticles, and protein aggregates. It can be used in a non-laboratory environment by individuals unfamiliar with microscopes.
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Polymeric micelles are drug carriers formed by the aggregation of some amphiphilic molecule with an amphiphilic block copolymer. These carriers form at some high concentration specific to the compounds used, called the critical micelle concentration. The addition of an amphiphilic block copolymer effectively lowers this critical micelle concentration by shifting the monomer exchange equilibrium. These carriers are comparable to liposomes, however the lack of an aqueous core makes polymeric micelles less accommodating to a wide variety of drugs.
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Fig. 3. Components of an influenza virosome In contrast to liposomes, virosomes contain functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase (NA) intercalated in the phospholipid bilayer membrane. They have a typical mean diameter of 150 nm. Essentially, virosomes represent reconstituted empty influenza virus envelopes, devoid of the nucleocapsid including the genetic material of the source virus.h The unique properties of virosomes partially relate to the presence of biologically active influenza HA in their membrane.
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Her lab became the national and international hub of Couette flow Linear Dichroism, allowing scientists to obtain structural and kinetic information about several systems. She demonstrated that it is possible to orient membrane systems of liposomes. Rodgers developed Raman Linear Difference Spectroscopy to study the division of bacterial cells. She designed a new instrument that could measure Raman optical activity and Raman Linear Difference Spectroscopy in an effort to probe the secondary and tertiary structures of biomacromolecules.
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This technique uses a patented Microfluidizer to obtain a greater amount of homogenous suspensions that can create smaller particles than homogenizers. A homogenizer is first used to create a coarse suspension which is then pumped into the microfluidizer under high pressure. The flow is then split into two streams which will react at very high velocities in an interaction chamber until desired particle size is obtained. This technique allows for large scale production of phospholipid liposomes and subsequent material nanoencapsulations.
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Nanoparticles range in size from 10 - 1000 nm (or 1 µm) and they can be made from natural or artificial polymers, lipids, dendrimers, and micelles. Most polymers used for nanoparticle drug delivery systems are natural, biocompatible, and biodegradable, which helps prevent contamination in the CNS. Several current methods for drug delivery to the brain include the use of liposomes, prodrugs, and carrier-mediated transporters. Many different delivery methods exist to transport these drugs into the body, such as peroral, intranasal, intravenous, and intracranial.
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A wide variety of drug carrier systems have been developed and studied, each of which has unique advantages and disadvantages. Some of the more popular types of drug carriers include liposomes, polymeric micelles, microspheres, and nanoparticles. Different methods of attaching the drug to the carrier have been implemented, including adsorption, integration into the bulk structure, encapsulation, and covalent bonding. Different types of drug carrier utilize different methods of attachment, and some carriers can even implement a variety of attachment methods.
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The transferrin was conjugated to the nanoparticle to target tumor cells that possess transferrin-receptor mediated endocytosis mechanisms on their membrane. This means of targeting was found to increase uptake, as opposed to non-conjugated nanoparticles. Active targeting can also be achieved by utilizing magnetoliposomes, which usually serves as a contrast agent in magnetic resonance imaging. Thus, by grafting these liposomes with a desired drug to deliver to a region of the body, magnetic positioning could aid with this process.
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For instance, cytotoxic agents or siRNA could be encapsulated in liposomes or viral vectors that only become activated upon proteolytic cleavage by a target MMP. Finally, the tumor-targeting properties of MMP inhibitors offer a potential strategy for identifying small tumors. Researchers could couple MMP inhibitors to imaging agents to help detect tumors before they spread. Though initial trials yielded disappointing results, MMP inhibitors offer significant potential for improving cancer treatment by slowing the process of cancer cell invasion and metastasis.
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Egg lecithin is usually extracted chemically using ethanol, acetone, petroleum ether but not benzene or hexane due to restrictions on residual solvents by the pharmaceutical regulations.ICH Topic Q3C (R4) Impurities: Guideline for Residual Solvents It is an emulsifier, especially for parenteral use since it does not need to be metabolized. In aqueous solution, its phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration and temperature. This results in a type of surfactant that is usually classified as amphipathic.
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A milestone discovery in the career of Jean Gruenberg was the identification and the characterization of an atypical inverted cone-shaped phospholipid, originally named lysobisphosphatidic acid (LBPA) and also known as bis(monoacylglycero)phosphate (BMP). Using specific monoclonal antibodies, LBPA/BMP was shown to be enriched in intralumenal vesicles of late endosomes and to regulate the intracellular transport and homeostasis of cholesterol. LBPA/BMP is also directly involved in the formation of intracellular vesicles within multivesicular endosomes and endosome-mimicking liposomes.
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Micrograph of periportal hepatic steatosis, as may be seen due to steroid use, trichrome stain Fatty change represents the intracytoplasmatic accumulation of triglycerides (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus (microvesicular fatty change). In this stage, liver cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving characteristic signet ring appearance (macrovesicular fatty change).
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Further the specificity of binding will enable targeted drug delivery to TNBC cells in the future as well. Due to the efficacy and promising potential of this technology, Auguste and her colleagues filed a patent for these cancer targeting liposomes in 2018. Auguste, along with her colleagues at Boston Children’s Hospital, has also pioneered a novel gene editing approach to treating TNBC. The developed a tumor-targeted nanolipogel system which targets tumors and enables CRISPR mediated knockout of Lipocalin2, a known breast cancer oncogene.
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In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the blood–brain barrier. Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.
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The functions of lipids include storing energy, signaling, and acting as structural components of cell membranes. Lipids have applications in the cosmetic and food industries as well as in nanotechnology. Scientists sometimes define lipids as hydrophobic or amphiphilic small molecules; the amphiphilic nature of some lipids allows them to form structures such as vesicles, multilamellar/unilamellar liposomes, or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits or "building-blocks": ketoacyl and isoprene groups.
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Nanoparticles have the additional advantage of enhanced transport once injected into the body as compared to microparticles. Nanoparticles are able to be transported through the porous extracellular matrix much easier and reach the lymph nodes where the T cells reside. Also, iron oxide nanoparticles have been used to take advantage of the superparamagnetic properties and to cluster both Signals to enhance T cell stimulation. Materials which have been used include poly (glycolic acid), poly(lactic-co-glycolic acid), iron-oxide, liposomes, lipid bilayers, sepharose, polystyrene and Polyisocyanopeptides.
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In liposomes Osawa (2009) showed FtsZ is capable of exerting a contractile force with no other proteins present. Erickson (2009) proposed how the roles of tubulin-like proteins and actin-like proteins in cell division became reversed in an evolutionary mystery. The use of the FtsZ ring in dividing chloroplasts and some mitochondria further establishes their prokaryotic ancestry. L-form bacteria that lack a cell wall do not require FtsZ for division, which implies that bacteria may have retained components of an ancestral mode of cell division.
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Lipid nanoparticles can be manufactured by high pressure homogenization, a current method used to produce parenteral emulsions. This process can ultimately form a uniform dispersion of small droplets in a fluid substance by subdividing particles until the desired consistency is acquired. This manufacturing process is already scaled and in use in the food industry, which therefore makes it more appealing for researchers and for the drug delivery industry. Liposomes can also be functionalized by attaching various ligands on the surface to enhance brain- targeted delivery.
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The GBA processed 132 individual experiments with volumes of several milliliters. The apparatus studied living cells, microorganisms used in ecological waste treatment, and the development of brine shrimp and wasp eggs, and other biomedical test models which are used in cancer research. One sample studied, Liposomes, consist of spherical structures that could be used to encapsulate pharmaceuticals. If this biological product can be formed properly, it could be used to deliver a drug to a specific tissue in the body, such as a tumor.
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Ionophores are chemical compounds that reversibly bind and transport ions through biological membranes in the absence of a protein pore. This can disrupt the membrane potential, and thus these substances could exhibit cytotoxic properties. Ionophores modify the permeability of biological membranes toward certain ions to which they show affinity and selectivity. Many ionophores are lipid-soluble and transport ions across hydrophobic membranes, such as lipid bilayers found in the living cells or synthetic vesicles (liposomes), or liquid polymeric membranes (carrier-based ion selective electrodes).
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Over the years, his team developed and improved the technique of reflection interference contrast microscopy – RICM (which is quantitative interference reflection microscopy – IRM) – a powerful tool to probe adhesion of membranes and thin films. Collaborations with theoreticians like Reinhard Lipowsky, Udo Seifert and Robijn Bruinsma have led to seminal works on adhesion of cell mimetic giant vesicles (also called liposomes). Another of his interests is the cytoskeleton and its dynamics. To study cytoskeletal dynamics, his team developed magnetic tweezers capable of exerting very small pulling forces.
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Calcein, also known as fluorexon, fluorescein complex, is a fluorescent dye with excitation and emission wavelengths of 495/515 nm, respectively, and has the appearance of orange crystals. Calcein self-quenches at concentrations above 70mM and is commonly used as an indicator of lipid vesicle leakage.Sendai virus induced leakage of liposomes containing gangliosides Yung Shyeng Tsao and Leaf Huang Biochemistry 1985 24 (5), 1092-1098 It is also used traditionally as a complexometric indicator for titration of calcium ions with EDTA, and for fluorometric determination of calcium.
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On the therapeutic side, he proposed ways for in situ delivery of drugs and enzymes to the affected organs, using sugar-bearing liposomes. He also worked on the therapy of systemic fungal infections by developing liposomal formulations. On the academic front, he contributed in developing the departments he helped establish at CMC Vellore and Delhi University into centes of excellence in research. His researches have been documented by way of over 150 scientific papers published in refereed journals and he has also edited a number of books.
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The roles of lysoPA, PA, and DAG in promoting membrane curvature do not preclude a role in recruiting proteins to the membrane. For instance, the Ca2+ requirement for the fusion of complex liposomes is not greatly affected by the addition of annexin I, though it is reduced by PLD. However, with annexin I and PLD, the extent of fusion is greatly enhanced, and the Ca2+ requirement is reduced almost 1000-fold to near physiological levels. Thus the metabolic, biophysical, recruitment, and signaling roles of PA may be interrelated.
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Attachment of liposomes or nanoparticles to the exterior of the lipid MB has also been explored to increase MB payload. Upon MB destruction with ultrasound, these smaller particles can extravasate into the tumor tissue. Furthermore, through attachment of these particles to MBs as opposed to co-injection, the drug is confined to the blood stream instead of accumulating in healthy tissues, and the treatment is relegated to the location of ultrasound therapy. This MB modification is particularly attractive for Doxil, a lipid formulation of Doxorubicin already in clinical use.
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An adjuvant is typically thought of as a substance used in combination with the antigen to produce a more substantial and robust immune response than that elicited by the antigen alone. This is achieved through three mechanisms: by affecting the antigen delivery and presentation, by inducing the production of immunomodulatory cytokines, and by affecting the antigen presenting cells (APC). Adjuvants can consist of many different materials, from cell microparticles to other particulated delivery systems (e.g. liposomes). Adjuvants are crucial in affecting the specificity and isotype of the necessary antibodies.
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Light scattering measurements can be applied to synthetic polymers, proteins, pharmaceuticals and particles such as liposomes, micelles, and encapsulated proteins. Measurements can be made in one of two modes which are un-fractionated (batch mode) or in continuous flow mode (with SEC, HPLC or any other flow fractionation method). Batch mode experiments can be performed either by injecting a sample into a flow cell with a syringe or with the use of discrete vials. These measurements are most often used to measure timed events like antibody-antigen reactions or protein assembly.
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To prevent the lung manifestations of CF, only 5–10% the normal amount of CFTR gene expression is needed. Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options, mainly because very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable.
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Antisense RNA-based treatment (also known as gene silencing therapy) involves (a) identifying bacterial genes that encode essential proteins (eg. the Pseudomonas aeruginosa genes acpP, lpxC, and rpsJ), (b) synthesizing single stranded RNA that is complementary to the mRNA encoding these essential proteins, and (c) delivering the single stranded RNA to the infection site using cell-penetrating peptides or liposomes. The antisense RNA then hybridizes with the bacterial mRNA and blocks its translation into the essential protein. Antisense RNA-based treatment has been shown to be effective in in vivo models of P. aeruginosa pneumonia.
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As of 2017, SAMs for most Siglecs have been reported, except for Siglec -6, -8, -11, -14, -15 and -16. Clustering of receptors and high-avidity binding, collectively known as multivalent binding, can enhance the effectiveness of SAMs in human body. Currently, advancements in glycoengineering have made use of SAM-decorated nanoparticles, SAM-decorated polymers and on-cell synthesis of SAMs to present SAMs to Siglecs. Liposomes crosslinked with SAMs also have been shown to aid in presenting antigens to antigen-presenting cells via the Siglec-1 or -7 pathways.
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The word liposome derives from two Greek words: lipo ("fat") and soma ("body"); it is so named because its composition is primarily of phospholipid. Liposomes were first described by British haematologist Alec D Bangham in 1961 (published 1964), at the Babraham Institute, in Cambridge. They were discovered when Bangham and R. W. Horne were testing the institute's new electron microscope by adding negative stain to dry phospholipids. The resemblance to the plasmalemma was obvious, and the microscope pictures served as the first evidence for the cell membrane being a bilayer lipid structure.
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The suitability of RFA for a particular tumor depends on multiple factors. RFA can usually be administered as an outpatient procedure, though may at times require a brief hospital stay. RFA may be combined with locally delivered chemotherapy to treat hepatocellular carcinoma (primary liver cancer). A method currently in phase III trials uses the low-level heat (hyperthermia) created by the RFA probe to trigger release of concentrated chemotherapeutic drugs from heat-sensitive liposomes in the margins around the ablated tissue as a treatment for Hepatocellular carcinoma (HCC).
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Bicelles are much smaller than liposomes, and so can be used in experiments such as NMR spectroscopy where the larger vesicles are not an option. Nanodiscs consist of a segment of bilayer encapsulated by an amphipathic protein coat, rather than a lipid or detergent layer. Nanodiscs are more stable than bicelles and micelles at low concentrations, and are very well-defined in size (depending on the type of protein coat, between 10 and 20 nm). Membrane proteins incorporated into and solubilized by Nanodiscs can be studied by a wide variety of biophysical techniques.
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This would reduce the energy needed to curve the membrane into a vesicle, making it easier for the clathrin cage to fix and stabilise the curved membrane. This points to a pioneering role for epsin in vesicle budding, as it provides both a driving force and a link between membrane invagination and clathrin polymerisation. In particular, epsin-1 shows specificity for the membrane glycophospholipid phosphatidylinositol-4,5-bisphosphate, however not all ENTH domains bind to this molecule. Binding causes tubulation of liposomes and in vivo this membrane-binding function is normally coordinated with clathrin polymerisation.
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The enhanced permeability and retention (EPR) effect is a controversial concept by which molecules of certain sizes (typically liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues. The general explanation that is given for this phenomenon is that, in order for tumor cells to grow quickly, they must stimulate the production of blood vessels. VEGF and other growth factors are involved in cancer angiogenesis. Tumor cell aggregates as small as 150–200 μm, start to become dependent on blood supply carried out by neovasculature for their nutritional and oxygen supply.
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Shortly after the first description of liposomes, by British haematologist Dr Alec D Bangham in 1961 (published 1964), at the Babraham Institute, in Cambridge, scientists first started to contemplate the possibility of employing them as transportation systems in the blood stream. Since then, there have been many advances in this area, and as of 2008 there were 11 clinically approved liposomal drugs targeting a variety of pathological conditions and illnesses, including fungal infections, hepatitis A, influenza and certain cancers. Now, scientists plan to take full advantage of the 40 years of progress in liposome development to enhance this transportation system by employing vesosomes.
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Many photosensitisers are poorly soluble in aqueous media, particularly at physiological pH, limiting their use. Alternate delivery strategies range from the use of oil-in-water (o/w) emulsions to carrier vehicles such as liposomes and nanoparticles. Although these systems may increase therapeutic effects, the carrier system may inadvertently decrease the "observed" singlet oxygen quantum yield (ΦΔ): the singlet oxygen generated by the photosensitiser must diffuse out of the carrier system; and since singlet oxygen is believed to have a narrow radius of action, it may not reach the target cells. The carrier may limit light absorption, reducing singlet oxygen yield.
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Since, Kost also proposed a novel approach for a glucose flux continuous biosensor and noninvasive detection of amniotic fluid for prenatal testing. Additional applications studied by Kost are the use of ultrasound for on-demand targeted delivery of drugs from liposomes, combined ultrasonic and enzymatic debridement of necrotic eschars and the use of ultrasound for more efficient cancer gene therapy. Nowadays, he study gene therapy approach for the treatment of psoriasis. The focus in these studies is on the effect of ultrasound on transport through tissues of no viral carriers developed by Kost complexed with miRNA.
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The quantitative analysis of nanomaterials showed that nanoparticles, nanotubes, nanocrystalline materials, nanocomposites, and graphene have been mentioned in 400000, 181000, 144000, 140000, and 119000 ISI-indexed articles, respectively, by Sep 2018. As far as patents are concerned, nanoparticles, nanotubes, nanocomposites, graphene, and nanowires have been played a role in 45600, 32100, 12700, 12500, and 11800 patents, respectively. Monitoring approximately 7000 commercial nano-based products available on global markets revealed that the properties of around 2330 products have been enabled or enhanced aided by nanoparticles. Liposomes, nanofibers, nanocolloids, and aerogels were also of the most common nanomaterials in consumer products.
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The first generation of drug delivery liposomes had a simple lipid composition and suffered from several limitations. Circulation in the bloodstream was extremely limited due to both renal clearing and phagocytosis. Refinement of the lipid composition to tune fluidity, surface charge density, and surface hydration resulted in vesicles that adsorb fewer proteins from serum and thus are less readily recognized by the immune system. The most significant advance in this area was the grafting of polyethylene glycol (PEG) onto the liposome surface to produce “stealth” vesicles, which circulate over long times without immune or renal clearing.
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Sonication can be used for the production of nanoparticles, such as nanoemulsions,Peshkovsky, A.S., Peshkovsky, S.L., Bystryak, S. "Scalable high-power ultrasonic technology for the production of translucent nanoemulsions", Chemical Engineering and Processing: Process Intensification, 2013. 69: p. 77–62. nanocrystals, liposomes and wax emulsions, as well as for wastewater purification, degassing, extraction of seaweed polysaccharides and plant oil, extraction of anthocyanins and antioxidants, production of biofuels, crude oil desulphurization, cell disruption, polymer and epoxy processing, adhesive thinning, and many other processes. It is applied in pharmaceutical, cosmetic, water, food, ink, paint, coating, wood treatment, metalworking, nanocomposite, pesticide, fuel, wood product and many other industries.
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These proteins are called membrane scaffolding proteins (MSP) and align in double belt formation. Nanodiscs are structurally very similar to discoidal high-density lipoproteins (HDL) and the MSPs are modified versions of apolipoprotein A1 (apoA1), the main constituent in HDL. Nanodiscs are useful in the study of membrane proteins because they can solubilise and stabilise membrane proteins and represent a more native environment than liposomes, detergent micelles, bicelles and amphipols. The art of making nanodiscs has progressed past using only the MSPs and lipids to make particles, leading to alternative strategies like peptide nanodiscs that use simpler proteins and synthetic nanodiscs that do not need any proteins for stabilization.
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Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release [ER, XR, XL] dosage) or to a specific target in the body (targeted-release dosage).Pharmaceutics: Drug Delivery and Targeting, p. 7-13 Sustained-release dosage forms are dosage forms designed to release (liberate) a drug at a predetermined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects. This can be achieved through a variety of formulations, including liposomes and drug-polymer conjugates (an example being hydrogels).
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He made significant contribution to the field of lipid bilayer membranes and liposomes, biodegradable polymers, tissue engineering, nanospheres (magnetic/fluorescent) and drug delivery.Mohammad N. Sarbolouki resume Sarbolouki was of the founding members of Iranian Society of Nanotechnology, Iranian Society of Proteomics and Iranian Chemical Society.٤٠ سال كوشش درمرزهاي دانش ازJPL ناسا تا آزمايشگاه بيوفيزيك دانشگاه تهران He founded the first Biomaterial Research Center in Iran as well as National Research Center for Genetic Engineering and Biotechnology, ICGEB headquarter in Iran. Sarbolouki was involved in science policy making at the national level and was instrumental in the advancement of interdisciplinary and applied research in Iran.
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Nonionic detergents solubilize membrane proteins gently and (largely) preserving their physiological function by interaction with the hydrophobic membrane regions embedded in the lipid bilayers of cell membranes. Above the so-called critical micelle concentration CMC [OTG: 9 mM, or 0.2772% (w/v)], mixed micelles of membrane proteins and surfactant molecules are formed, with OTG concentrations of 1.1-1.2% (w/v) for the solubilization of membrane proteins from E. coli. No denaturation of the membrane proteins was found after solubilization with octylthioglucoside. For the analysis of the biological activity of membrane proteins, it is often necessary to reconstitute the proteins into the lipid bilayers of liposomes.
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Liposomes (a spherical vesicle having at least at least one lipid bilayer) of lipids from archaea typically demonstrate extremely low permeability for molecules and ions, even including protons. The ion permeability induced by ionophores (ion transporters across the membranes) are also quite low, and only comparable to that of egg phosphatidylcholine (a very common biological membrane component) at 37˚C when the temperature rises up to c.a. 70˚C. Compared to bacteria and eukarya, the isoprenoid side chains of archaeol are highly branched. This structural difference is believed lower the permeability of archaea over the whole growth temperature range which enables archaea to adapt to extreme environments.
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For use in pharmaceutical products, extrusion through nano-porous, polymeric filters is being used to produce suspensions of lipid vesicles liposomes or transfersomes with a particular size of a narrow size distribution. The anti-cancer drug Doxorubicin in liposome delivery system is formulated by extrusion, for example. Hot melt extrusion is also utilized in pharmaceutical solid oral dose processing to enable delivery of drugs with poor solubility and bioavailability. Hot melt extrusion has been shown to molecularly disperse poorly soluble drugs in a polymer carrier increasing dissolution rates and bioavailability. The process involves the application of heat, pressure and agitation to mix materials together and ‘extrude’ them through a die.
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Neuropeptide Y Neuropeptides are small proteins produced by neurons that act on G protein-coupled receptors and are responsible for slow-onset, long- lasting modulation of synaptic transmission. Neuropeptides often coexist with each other or with other neurotransmitters in single neurons. According to their chemical nature, coexisting messengers are localized to different cell compartments: neuropeptides are packaged in large granular vesicles (LGVs), whereas low-molecular weight neurotransmitters are stored in small synaptic vesicles. Neuropeptides conjugated to proteins or other carriers, such as liposomes, may be used for targeting radioisotopes or drugs to cells, specialized endothelia, and normal or neoplastic tissues expressing the corresponding binding sites for diagnostic or therapeutic purposes.
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Sedimentation field flow fractionation (SFFF) is a non-destructive separation technique which can be used for both separation, and collecting fractions. Some applications of SFFF include characterization of particle size of latex materials for adhesives, coatings and paints, colloidal silica for binders, coatings and compounding agents, titanium oxide pigments for paints, paper and textiles, emulsion for soft drinks, and biological materials like viruses and liposomes. Some main aspects of SFFF include: it provides high- resolution possibilities for size distribution measurements with high precision, the resolution is dependent on experimental conditions, the typical analysis time is 1 to 2 hours, and it is a non-destructive technique which offers the possibility of collecting fraction.
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Drug delivery is a rapidly growing area that is now taking advantage of nanotube technology. Systems being used currently for drug delivery include dendrimers, polymers, and liposomes, but carbon nanotubes present the opportunity to work with effective structures that have high drug loading capacities and good cell penetration qualities. These nanotubes function with a larger inner volume to be used as the drug container, large aspect ratios for numerous functionalization attachments, and the ability to be readily taken up by the cell. Because of their tube structure, carbon nanotubes can be made with or without end caps, meaning that without end caps the inside where the drug is held would be more accessible.
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Increasing the mole percent of PEG on the surface of the liposomes by 4-10% significantly increased circulation time in vivo from 200 to 1000 minutes. PEGylation of the liposomal nanocarrier elongates the half-life of the construct while maintaining the passive targeting mechanism that is commonly conferred to lipid-based nanocarriers. When used as a delivery system, the ability to induce instability in the construct is commonly exploited allowing the selective release of the encapsulated therapeutic agent in close proximity to the target tissue/cell in vivo. This nanocarrier system is commonly used in anti-cancer treatments as the acidity of the tumour mass caused by an over- reliance on glycolysis triggers drug release.
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Roux et al., « Conception and realization of a non cationic non viral DNA vector », Current Medical Chemistry, 10, (2004), p. 1241-1253 Subsequently, and led initially by chance to a discovery, he systematically worked towards applications of his work and those of others. The industrialization of a discovery-based technology: the production of "Spherulites "Didier Roux et Olivier Diat, « Procédé de fabrication de microcapsules ou de liposomes de taille contrôlée », Brevet Francais FRA 2689418, 1992 and the development of a measuring instrument that has been commercialized (the RheoScope)D. Roux, P. Sierro, « Appareil et procédés de mesure sur un fluide en écoulement avec cisaillement », Brevet Francais délivré FR 9715577, 1997 are examples.
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Solid lipid nanoparticles (SLNs) are a new pharmaceutical delivery system or pharmaceutical formulation. The conventional approaches such as use of permeation enhancers, surface modification, prodrug synthesis, complex formation and colloidal lipid carrier based strategies have been developed for the delivery of drugs to intestinal lymphatics. In addition, polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions, micellar solutions and recently solid lipid nanoparticles (SLN) have been exploited as probable possibilities as carriers for oral intestinal lymphatic delivery.Studies on binary lipid matrix based solid lipid nanoparticles of repaglinide: in vitro and in vivo evaluation. Rawat MK, Jain A and Singh S, Journal of Pharmaceutical Sciences, 2011, volume 100, issue 6, pages 2366-2378 A solid lipid nanoparticle is typically spherical with an average diameter between 10 and 1000 nanometers.
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Crenezumab was developed by Ruth Greferath, Ph.D., and Claude Nicolau, Ph.D., before the Swiss-based biopharmaceutical company AC Immune was founded, which focuses on developing targeted therapeutics for misfolded proteins that cause neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. AC Immune was founded in 2003 by current CEO Andrea Pfeifer, Ph.D. and funded primarily by German billionaire Dietmar Hopp. In 2016, AC Immune filed for an IPO valuing the company at $700 million and subsequently sold 6.9 million shares for net proceeds of $68.73 million. To develop crenezumab, AC Immune utilized its SupraAntigen technology, which involves injecting mice with liposomes that contain several hundred peptide mimics of antigens in order to generate a multitude of antibodies, from which the ones with best specificity are selected.
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SeV induces the production of B cell-activating factor by monocytes and by some other cells. Heat-inactivated SeV virus induces the production of IL-10 and IL-6 cytokines by dendritic cells (DC). Most likely, F protein is responsible for this induction because reconstituted liposomes containing F protein can stimulate IL-6 production by DC. The production of IL-6 in response to SeV infection is restricted to conventional dendritic cells (DCs) subsets, such as CD4+ and double negative (dnDC). The UV-inactivated SeV (and likely the alive virus as well) can stimulate dendritic cells to secrete chemokines and cytokines such as interleukin-6, interferon-beta, chemokine (C-C motif) ligand 5, and chemokine (C-X-C motif) ligand 10.
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Heat-inactivated SeV virus induces the production of IL-10 and IL-6 cytokines by dendritic cells (DC). Most likely, F protein is responsible for this induction because reconstituted liposomes containing F protein can stimulate IL-6 production by DC. The production of IL-6 in response to SeV infection is restricted to conventional dendritic cells (DCs) subsets, such as CD4+ and double negative (dnDC). The UV-inactivated SeV (and likely the alive virus as well) can stimulate dendritic cells to secrete chemokines and cytokines such as interleukin-6, interferon-beta, chemokine (C-C motif) ligand 5, and chemokine (C-X-C motif) ligand 10. These molecules activate both CD8+ T cells as well as natural killer cells and attract them to the tumor.
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The limitation of the intra-membrane mobility of supported lipid bilayers can be overcome by introducing half- membrane spanning tether lipids with benzyl disulphide (DPL) and synthetic archaea analogue full membrane spanning lipids with phytanoly chains to stabilize the structure and polyethyleneglycol units as a hydrophilic spacer. Bilayer formation is achieved by exposure of the lipid coated gold substrate to outer layer lipids either in an ethanol solution or in liposomes. The advantage of this approach is that because of the hydrophilic space of around 4 nm, the interaction with the substrate is minimal and the extra space allows the introduction of protein ion channels into the bilayer. Additionally the spacer layer creates an ionic reservoir that readily enables ac electrical impedance measurement across the bilayer.
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Specificity of folate conjugates for the FR has been shown by competition tests with free folate. When this ligand, known to bind the FR, is added in excess of the folate conjugate, it outcompetes the conjugate, indicating that the folate conjugate specifically binds the FR, and not other receptors, in the process of receptor-mediated endocytosis. Addition of an enzyme that frees the folate receptor from the cell membrane and addition of antibodies to the FR also reverse the internalization of folate conjugates, providing further evidence that folate conjugates bind the FR with specificity. While some drugs and radioimaging agents are delivered to cells as folate conjugates in a one-to-one folate-to-conjugate ratio, folate- targeted liposomes allow for the delivery of larger amounts of chemotherapeutic agents.
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Adjuvants in immunology are often used to modify or augment the effects of a vaccine by stimulating the immune system to respond to the vaccine more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionarily conserved molecules, so called PAMPs, which include liposomes, lipopolysaccharide (LPS), molecular cages for antigens, components of bacterial cell walls, and endocytosed nucleic acids such as double-stranded RNA (dsRNA), single-stranded DNA (ssDNA), and unmethylated CpG dinucleotide-containing DNA. Because immune systems have evolved to recognize these specific antigenic moieties, the presence of an adjuvant in conjunction with the vaccine can greatly increase the innate immune response to the antigen by augmenting the activities of dendritic cells (DCs), lymphocytes, and macrophages by mimicking a natural infection.
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Magnetic nanoparticle-based drug delivery is a means in which magnetic particles such as iron oxide nanoparticles are a component of a delivery vehicle for magnetic drug delivery, due to their easiness and simplicity with magnet-guidance. Magnetic nanoparticles can impart imaging and controlled release capabilities to drug delivery materials such as micelles, liposomes, and polymers. Molecular magnets (single-molecule magnets) are a platform that incorporates insoluble (toxic) drugs into biocompatible carrier materials, without adding magnetic iron oxide nanoparticles, in which adversely affecting potential side effects attributed to iron overdose, as well as low drug loading efficiency. The drawbacks in conventional magnetic drug delivery methods can be overcame by switching from typical iron oxide nanoparticles to ones based on molecular magnet, such as Fe(salen)-based "anticancer nanomagnet" with proven cancer-fighting ability.
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Bimal Kumar Bachhawat (1925–1996) was an Indian neurochemist and glycobiologist, known for his discovery of HMG-CoA lyase, an intermediate in the mevalonate and ketogenesis pathway, and for the elucidation of the molecular cause of Metachromatic leukodystrophy, a hereditary disease of the brain His studies on sugar-bearing liposomes led to its use as a carrier for in situ delivery of drugs and hormones to diseased organs and he pioneered the therapy of systemic fungal infections using liposomal formulations. He was a recipient of several awards including the Shanti Swarup Bhatnagar Award, the highest Indian honor in science and technology and an elected fellow of three major Indian science academies. The Government of India awarded him the third highest civilian honour of the Padma Bhushan, in 1990, for his contributions to science.
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In 2005 Ben Goldacre, investigating for his Bad Science column in The Guardian, examined Penta's website and found that Penta Water had many health claims and testimonials on their website. When he reached out to Penta for scientific evidence, he was told that there exists an in vitro study on liposomes with aquaporins in artificial membranes that demonstrates this water is absorbed faster, although this study was never produced. Ben Goldacre claims he received threatening messages from Penta Water in the form of a message to his Bad Science column that read "Sleep well tonight and think about how and why you tried to fuck us over and practice [sic] keeping one eye open", but he claims they also apologized for this remark. Penta Water claimed that seeds could germinate in half the time in Penta Water, compared to normal water.
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