Elsewhere, chemotherapy drugs have been attached to nanodiamonds, delivered via DNA-string "nanotrains," and encapsulated in liposome nanoparticles.
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These contact sites begin to unzip and break down, opening up a channel from the virus into the interior of the liposome.
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The approval was largely expected and follows the agency's advisory committee backing the drug, Arikayce (amikacin liposome inhalation suspension), in a meeting in early August.
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Specifically, they chronicled the merger of the influenza virus and a small lipid vesicle (or liposome), which was used as a stand-in for a cellular membrane.
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Around the same time, Yarosh led a phase III clinical trial in which test subjects prone to skin cancer applied a T4N5 liposome lotion for one year.
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Using lipids other than phosphatidylcholine can greatly facilitate liposome preparation.
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It was Weissmann who proposed the more user-friendly term liposome.
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The safety and efficacy of amikacin liposome inhalation suspension, an inhaled treatment taken through a nebulizer, was demonstrated in a randomized, controlled clinical trial where patients were assigned to one of two treatment groups. One group of patients received amikacin liposome inhalation suspension plus a background multi-drug antibacterial regimen, while the other treatment group received a background multi-drug antibacterial regimen alone. By the sixth month of treatment, 29 percent of patients treated with amikacin liposome inhalation suspension had no growth of mycobacteria in their sputum cultures for three consecutive months compared to 9 percent of patients who were not treated with amikacin liposome inhalation suspension.
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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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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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Inhaled ciclosporin formulations are in clinical development, and include a solution in propylene glycol and liposome dispersions..
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The absolute stereochemistry at these carbons is responsible for vincristine's anticancer activity. The liposome encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the neurotoxicity associated with it. Liposome encapsulation increases vincristine's plasma concentration and circulation lifetime in the body, and allows the drug to enter cells more easily.
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Substitution would be desirable because liposome-encapsulated doxorubicin is less cardiotoxic than unencapsulated doxorubicin. This liposome-encapsulated form is also approved by the FDA for treatment of ovarian cancer and multiple myeloma. A non- pegylated liposomal doxorubicin, called Myocet, is approved in Europe and Canada for treatment of metastatic breast cancer in combination with cyclophosphamide, but has not been approved by the FDA for use in the United States. Unlike Doxil, the Myocet liposome does not have a polyethylene glycol coating, and therefore does not result in the same rate of hand-foot syndrome.
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Lipoplexes are liposome structures characterized by a bilayer lipid membrane. Lastly, micelles result from electrostatic interaction between nucleic acids and copolymers.
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Liposome encapsulation improves the efficacy and increases the half- life of OSI-7904. Its effect on solid tumors is currently under evaluation.
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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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Amikacin liposome inhalation suspension was the first drug approved under the US limited population pathway for antibacterial and antifungal drugs (LPAD pathway). It also was approved under the accelerated approval pathway. The U.S. Food and Drug Administration (FDA) granted the application for amikacin liposome inhalation suspension fast track, breakthrough therapy, priority review, and qualified infectious disease product (QIDP) designations. The FDA granted approval of Arikayce to Insmed, Inc.
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Another novel acoustically responsive MB system is the direct encapsulation of MBs inside of a liposome. Theses systems circulate longer in the body than MBs alone do, as this packaging method prevents the MB from dissolving in the blood stream. Hydrophilic drugs persist in the aqueous media inside the liposome, while hydrophobic drugs congregate in the lipid bilayer. It has been shown in vitro that macrophages do not engulf these particles.
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The amikacin liposome inhalation suspension prescribing information includes a boxed warning regarding the increased risk of respiratory conditions including hypersensitivity pneumonitis (inflamed lungs), bronchospasm (tightening of the airway), exacerbation of underlying lung disease and hemoptysis (spitting up blood) that have led to hospitalizations in some cases. Other common side effects in patients taking amikacin liposome inhalation suspension are dysphonia (difficulty speaking), cough, ototoxicity (damaged hearing), upper airway irritation, musculoskeletal pain, fatigue, diarrhea and nausea.
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Amphipathic Lipid Packing Sensor (ALPS) motifs were first identified in 2005 in ARFGAP1 and have been reviewed. adsorb to) curved lipid bilayers. The curving of a phospholipid bilayer, for example into a liposome, causes disturbances to the packing of the lipids on the side of the bilayer that has the larger surface area (the outside of a liposome for example). The less "ordered" or "looser" packing of the lipids is recognized by ALPS motifs.
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Fusion between cationic vesicles and cell surfaces can deliver the DNA directly across the plasma membrane. This process bypasses the endosomal-lysosomal route which leads to degradation of anionic liposome formulations.
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However, microRNA mimics and antagomirs suffer from a lack of stability in vivo and lack an accurate delivery system to target these molecules to the tumor cells or tissue for treatment. Improvements to antagomir and microRNA mimic stability through chemical modifications such as locked nucleic acid (LNA) oligonucleotides or peptide nucleic acids (PNA) can prevent the fast clearing of the these small molecules by RNases. Delivery of antagomirs and microRNA mimics into cells by enclosing these molecules in liposome-nanoparticles has generated interest however liposome structures suffer from their own drawbacks that will need to be overcome for their effective use as a drug delivery mechanism. These drawbacks of liposome- nanoparticles include nonspecific uptake by cells and induction of immune responses.
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It contains the EQVSHHPP sequence. It has an hydrophobic pocket that binds a sterol and also contains multiple membrane binding surfaces which permit the protein to have the ability to cause liposome aggregation.
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A mechanism for liposome transport across the BBB is lipid- mediated free diffusion, a type of facilitated diffusion, or lipid-mediated endocytosis. There exist many lipoprotein receptors which bind lipoproteins to form complexes that in turn transport the liposome nano-delivery system across the BBB. Apolipoprotein E (apoE) is a protein that facilitates transport of lipids and cholesterol. ApoE constituents bind to nanoparticles, and then this complex binds to a low-density lipoprotein receptor (LDLR) in the BBB and allows transport to occur.
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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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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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A liposome encapsulated version of irinotecan sold as Onivyde by Merrimack Pharmaceuticals, was approved by FDA in October 2015, to treat metastatic pancreatic cancer. It was approved for medical use in the European Union in October 2016.
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Inhaled ciclosporin has also shown promise in several other lung conditions. Early stage studies in mice have shown some benefit of ciclosporin as an adjuvant therapy in lung cancer when administered as a liposome aerosol in conjunction with paclitaxel.
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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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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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"Effect of membrane composition and of co-encapsulation of immunostimulants in a liposome-entrapped crotoxin", Biotechnol. Appl. Biochem., 33, 61-64. It has been reported that mice can develop a tolerance to the toxin when they get increasing doses of crotoxin every day.
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Another treatment method is the utilisation of electricity as the membrane- permeabilizing agent (electroporation or electrotransformation). Finally, liposome-mediated transformation can be used. In this method DNA is coated with lipid. Fusion of this lipid and the membrane lipid can occur, facilitating the entry of DNA.
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Vesosome structure has taken advantage of the progress in liposome development as steric stabilization, pH loading of drugs (it is loaded by pH gradient), and intrinsic biocompatibility (it can be modified with a variety of agents, for example to specifically target a disease site, or promote adhesion or fusion).
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Receptor-mediated DNA uptake could be facilitated by the presence of polyguanylate sequences. Gene gun delivery systems, cationic liposome packaging, and other delivery methods bypass this entry method, but understanding it may be useful in reducing costs (e.g. by reducing the requirement for cytofectins), which could be important in animal husbandry.
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Doxorubicin is photosensitive, and containers are often covered by an aluminum bag and/or brown wax paper to prevent light from affecting it. Doxorubicin is also available in liposome- encapsulated forms as Doxil (pegylated form), Myocet (nonpegylated form), and Caelyx, although these forms must also be given by intravenous injection.
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OSI-7904 is a noncompetitive liposomal thymidylate synthase inhibitor. OSI-7904 is a benzoquinazoline folate analog with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resulting in inhibition of thymine nucleotide synthesis and DNA replication. OSI-7904L is a liposome-encapsulated formulation of OSI-7904.
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Many variations for artificial cell preparation and encapsulation have been developed. Typically, vesicles such as a nanoparticle, polymersome or liposome are synthesized. An emulsion is typically made through the use of high pressure equipment such as a high pressure homogenizer or a Microfluidizer. Two micro-encapsulation methods for nitrocellulose are also described below.
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An liposome inhalation suspension is also available and approved to treat Mycobacterium avium complex (MAC) in the United States. The application for Arikayce was withdrawn in the European Union because the Committee for Medicinal Products for Human Use (CHMP) was of the opinion that the benefits of Arikayce did not outweigh its risks.
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Effectene Reagent spontaneously forms micelle structures exhibiting no size or batch variation (as may be found with pre-formulated liposome reagents). This feature ensures reproducibility of transfection-complex formation. The process of highly condensing DNA molecules and then coating them with Effectene Reagent is an effective way to transfer DNA into eukaryotic cells.
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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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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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MF59 is an oil- in-water emulsion of squalene adjuvant used in some human vaccines. Over 22 million doses of a vaccine with squalene have been administered with no safety concerns. The plant extract QS21 is a liposome made up of plant saponins. It is a part of the Shingrix vaccine approved in 2017.
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This method was able to reduce tumor growth by 77% without toxicity to healthy tissues. The system again uses the approach of targeting ICAM-1 on TNBC cells via antibody binding of the liposome to the cells in order to specifically infect tumor cells. This article was also published in the Proceedings of the National Academy of Sciences.
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Alternatives included aerosol instillation of naked DNA on mucosal surfaces, such as the nasal and lung mucosa, and topical administration of pDNA to the eye and vaginal mucosa. Mucosal surface delivery has also been achieved using cationic liposome-DNA preparations, biodegradable microspheres, attenuated Salmonalla, Shigella or Listeria vectors for oral administration to the intestinal mucosa and recombinant adenovirus vectors.
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Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, which are the final degradation products of fats and lipids. Lipids, especially phospholipids, are also used in various pharmaceutical products, either as co- solubilisers (e.g., in parenteral infusions) or else as drug carrier components (e.g., in a liposome or transfersome).
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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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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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This fluid lipid bilayer cross section is made up entirely of phosphatidylcholine. The three main structures phospholipids form in solution; the liposome (a closed bilayer), the micelle and the bilayer. The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells.
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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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Interleukin-1 receptor-associated kinase 3 is an enzyme that in humans is encoded by the IRAK3 gene. Using in vivo liposome-mediated delivery of CRISPR/Cas9 plasmid expressing IRAK3 gRNA, IRAK3 was shown to be responsible for endotoxin-induced expression of A20 and VE-cadherin in endothelial cells. Thus, IRAK3 is crucial for maintenance and repair of endothelial barrier after endotoxin-induced lung injury.
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Vesicles can be formed with molecules and ions inside the vesicle by forming the vesicle with the desired molecule or ion present in the solution. Proteins can also be embedded into the membrane through solubilizing the desired proteins in the presence of detergents and attaching them to the phospholipids in which the liposome is formed. These provide researchers with a tool to examine various membrane protein functions.
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Auguste pursued her undergraduate studies at the Massachusetts Institute of Technology in 1995. She majored in chemical engineering and graduated in 1999 with her Bachelors of Science. Following her undergraduate degree, Auguste pursued her Master's and her PhD in chemical engineering at Princeton University. She studied under the mentorship of Robert K. Prud’homme, where she designed and tested novel liposome structures for potential use in drug delivery platforms.
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This plasmid can be inserted into either bacterial or animal cells. Introducing DNA into bacterial cells can be done by transformation via uptake of naked DNA, conjugation via cell-cell contact or by transduction via viral vector. Introducing DNA into eukaryotic cells, such as animal cells, by physical or chemical means is called transfection. Several different transfection techniques are available, such as calcium phosphate transfection, electroporation, microinjection and liposome transfection.
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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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The three main structures phospholipids form in solution; the liposome (a closed bilayer), the micelle and the bilayer. Self-assembled vesicles are essential components of primitive cells. The second law of thermodynamics requires that the universe move in a direction in which disorder (or entropy) increases, yet life is distinguished by its great degree of organization. Therefore, a boundary is needed to separate life processes from non-living matter.
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This proves further long term in vivo studies are needed to gain enough understanding to allow for successful clinical trials. One of the most common nano-based drug delivery platforms is liposome-based delivery. They are both lipid-soluble and nano-scale and thus are permitted through a fully functioning BBB. Additionally, lipids themselves are biological molecules, making them highly biocompatible, which in turn lowers the risk of cell toxicity.
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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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The most prevalent construct is the "Magnetoliposome", which is a liposome with magnetic nanoparticles typically embedded in the lipid bilayer. Under an alternating magnetic field, the magnetic nanoparticles are heated, and this heat permeabilizes the membrane. This causes release of the loaded drug. This treatment option has a lot of potential as the combination of hyperthermia and drug release is likely to treat tumors better than either option alone, but it is still under development.
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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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If there is only one phospholipid bilayer, they are called unilamellar liposome vesicles; otherwise they are called multilamellar. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.
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Non-viral methods include physical methods such as electroporation, microinjection, gene gun, impalefection, hydrostatic pressure, continuous infusion, and sonication and chemical, such as lipofection, which is a lipid-mediated DNA-transfection process utilizing liposome vectors. It can also include the use of polymeric gene carriers (polyplexes). Virus mediated gene delivery utilizes the ability of a virus to inject its DNA inside a host cell. A gene that is intended for delivery is packaged into a replication-deficient viral particle.
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Since they are coated with leukocytes, the nanosponges will pull towards a location of infection or foreign matter in the body. The nanosponges avoid macrophage attack because they are coated with natural materials. Researchers have only tested these in lab animals but suggest the liposome nanosponge could be easier to get approved by the FDA for in-patient use. Researchers have found promising results in using these nanosponges in drug delivery, relieving inflammation, and repairing damaged tissue.
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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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Adamala's work includes contributions to the field of astrobiology, synthetic cell engineering and biocomputing.. Her research on prebiotic RNA replication provided an experimental scenario for the RNA world hypothesis of the origin of life. She has worked on constructing liposome bioreactor synthetic cells. She is a founder and steering group member of the Build-a-Cell Initiative, an international collaboration for creation of synthetic live cells. She is also co-founder of synthetic cell company Synlife.
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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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There is a pegylated (polyethylene glycol coated) liposome-encapsulated form of doxorubicin, sold as Doxil. It was developed to treat Kaposi's sarcoma, an AIDS-related cancer that causes lesions to grow under the skin, in the lining of the mouth, nose and throat, or in other organs. The polyethylene glycol coating results in preferential concentration of doxorubicin in the skin. However, this also results in a side effect called palmar plantar erythrodysesthesia (PPE), more commonly known as hand-foot syndrome.
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Magnet- assisted transfection is a relatively new and time-saving method to introduce nucleic acids into a target cell with increased efficiency. In particular, adherent mammalian cell lines and primary cell cultures show very high transfection rates. Suspension cells and cells from other organisms can also be successfully transfected. A major advantage of the method is the mild treatment of the cells in comparison to liposome-based transfection reagents (lipofection) and electroporation, which may result in the death of 20-50% of cells.
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The EPR effect is further enhanced by many pathophysiological factors involved in enhancement of the extravasation of macromolecules in solid tumor tissues. For instance, bradykinin, nitric oxide / peroxynitrite, prostaglandins, vascular permeability factor (also known as vascular endothelial growth factor VEGF), tumor necrosis factor and others. One factor that leads to the increased retention is the lack of lymphatics around the tumor region which would filter out such particles under normal conditions. The EPR effect is usually employed to describe nanoparticle and liposome delivery to cancer tissue.
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DepoDur CII, previously known as DepoMorphine, is a morphine sulfate extended- release liposome injection (see Depot injection), product of Pacira Pharmaceuticals (formerly SkyePharma PLC). It was approved by the U.S. Food and Drug Administration (FDA) in 2004 for use as a post-surgical pain reliever. In Europe, it was approved by the Medicines and Healthcare products Regulatory Agency in 2006. It is a one-time injection (during or shortly after surgery) that maintains a therapeutically effective level of morphine in the patient's bloodstream for 48 hours.
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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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Several research groups have been developing GM zebrafish to detect aquatic pollution. The laboratory that developed the GloFish originally intended them to change color in the presence of pollutants, as environmental sentinels.National University of Singapore Enterprise webpage Teams at the University of Cincinnati and Tulane University have been developing GM fish for the same purpose. Several transgenic methods have been used to introduce target DNA into zebrafish for environmental monitoring, including micro- injection, electroporation, particle gun bombardment, liposome-mediated gene transfer, and sperm-mediated gene transfer.
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Reflection-absorption infrared, dual polarisation interferometry, surface-enhanced Raman spectroscopy and sum-frequency generation spectroscopy can be used to probe solid–vacuum as well as solid–gas, solid–liquid, and liquid–gas surfaces. Multi-parametric surface plasmon resonance works in solid–gas, solid–liquid, liquid–gas surfaces and can detect even sub-nanometer layers. It probes the interaction kinetics as well as dynamic structural changes such as liposome collapse or swelling of layers in different pH. Dual-polarization interferometry is used to quantify the order and disruption in birefringent thin films.
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In May 2016, Merrimack announced their partnership with Baxalta for an upcoming phase 1 clinical trial. Merrimack's MM-151 and ONIVYDE® (irinotecan liposome injection, also known as nal-IRI) will be used in combination to treat metastatic colorectal cancer. ONIVYDE® is FDA approved and has been successful in treating metastatic adenocarcinoma of the pancreas by inhibiting topoisomerase I function. The study will begin as a phase 1 safety clinical trial, but is planned to transfer into a phase 2 efficacy study after the maximum dosage is determined.
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In fact, despite improvements in outcome associated with acute rejection, virtually no improvement in survival has been noted in chronic rejection over the last 20 years. The surprising finding that aerosolized ciclosporin may prevent or delay development of this insidious condition has led to renewed interest with aerosolized ciclosporin formulations and one early stage trial involving a dry powder inhaler is recruiting while another phase III trial involving nebulized ciclosporin in propylene glycol is underway. Early studies have also been conducted with liposome formulations in volunteers and patients.
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Zinc oxide and titanium oxide are often used in sun screen to provide broad protection from UVA and UVB ranges. Eating certain foods may decrease the risk of sunburns but this is much less than the protection provided by sunscreen. A meta-analysis of skin cancer prevention in high risk individuals found evidence that topical application of T4N5 liposome lotion reduced the rate of appearance of basal cell carcinomas in people with xeroderma pigmentosum, and that acitretin taken by mouth may have a skin protective benefit in people following kidney transplant.
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Plant thylakoid membranes have the largest lipid component of a non-bilayer forming monogalactosyl diglyceride (MGDG), and little phospholipids; despite this unique lipid composition, chloroplast thylakoid membranes have been shown to contain a dynamic lipid-bilayer matrix as revealed by magnetic resonance and electron microscope studies. Self- organization of phospholipids: a spherical liposome, a micelle, and a lipid bilayer. A biological membrane is a form of lamellar phase lipid bilayer. The formation of lipid bilayers is an energetically preferred process when the glycerophospholipids described above are in an aqueous environment.
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To address this problem, Wächtershäuser proposed that concentration might occur by concentration upon ("adsorption to") the surfaces of minerals. With the accumulation of enough amphipathic molecules (such as phospholipids), a bilayer will self-organize, and any molecules caught inside will become the contents of a liposome, and would be concentrated enough to allow chemical reactions to transform organic molecules into prebiotic molecules. Although developed for his own iron-sulfur world model, the idea of the primordial sandwich has also been adopted by some adherents of the RNA world model.
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The three main structures phospholipids form spontaneously in solution: the liposome (a closed bilayer), the micelle and the bilayer. A protocell is a self-organized, self-ordered, spherical collection of lipids proposed as a stepping-stone to the origin of life. A central question in evolution is how simple protocells first arose and differed in reproductive contribution to the following generation driving the evolution of life. Although a functional protocell has not yet been achieved in a laboratory setting, there are scientists who think the goal is well within reach.
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Liposome formulations that encapsulate anti-cancer drugs for selective uptake to tumors via the EPR effect include: Doxil and Myocet, both of which encapsulate doxorubicin (a DNA intercalator and common chemotherapeutic); DaunoXome, which encapsulates daunorubicin (a similar DNA intercalator); and Onco-TCS, which encapsulates vincristine (a molecule that induces formation of microtubules, dysregulating cell division). Another novel utilization of the EPR effect comes from Protein-bound paclitaxel (marketed under the trade name Abraxane) where paclitaxel (a molecule which dysregulates cell division via stabilization of microtubules) is bound to albumin to add bulk and aid delivery.
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Nastruzzi was educated in pharmaceutical technology at the School of Pharmacy of the University of Ferrara, working on the isoxazole chemistry. Subsequently, he obtained the PhD in Pharmaceutical Sciences working on liposome based formulations and later he was a postdoctoral fellow at Institute fur Polymere at ETH, Zurich, under the supervision of Prof. Pier Luigi Luisi. Nastruzzi is currently professor at the Department of Chemical and Pharmaceutical Sciences at the University of Ferrara, where he founded the Biomaterials and Encapsulation Laboratory (BEL) dealing with research in the field of drug delivery and controlled release.
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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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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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Mild hyperthermia, which provides temperatures equal to that of a naturally high fever, may stimulate natural immunological attacks against the tumor. However it is also induces a natural physiological response called thermotolerance, which tends to protect the treated tumor. Moderate hyperthermia, which heats cells in the range of , damages cells directly, in addition to making the cells radiosensitive and increasing the pore size to improve delivery of large-molecule chemotherapeutic and immunotherapeutic agents (molecular weight greater than 1,000 Daltons), such as monoclonal antibodies and liposome-encapsulated drugs. Cellular uptake of certain small molecule drugs is also increased.
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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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When encapsulated in liposome nanoparticle, staurosporine is shown to suppress tumors in vivo in a mouse model without the toxic side effects which have prohibited its use as an anti-cancer drug with high apoptotic activity. Researchers in UC San Diego Moores Cancer Center develop a platform technology of high drug-loading efficiency by manipulating the pH environment of the cells. When injected into the mouse glioblastoma model, staurosporine is found to accumulate primarily in the tumor via fluorescence confirmation, and the mice did not suffer weight loss compared to the control mice administered with the free compound, an indicator of reduced toxicity.
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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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The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9. A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.
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Since PAMAM dendrimers and their complexes with DNA exhibit low cytotoxicity, higher transfection efficiencies than liposome-based methods, and are effective across a broad range of cell lines, they have taken an important place in modern gene therapy methodologies. The biotechnology company Qiagen currently offers two DNA transfection product lines (SuperFect and PolyFect) based on activated PAMAM dendrimer technology. Much work lies ahead before activated PAMAM dendrimers can be used as in vivo gene therapy agents. Although the dendrimers have proved to be highly efficient and non-toxic in vitro, the stability, behavior, and transport of the transfection complex in biological systems has yet to be characterized and optimized.
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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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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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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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L1CAM synthesis inhibition using siRNA Because L1CAM is considered to be a key factor in metastasis, it has been suggested that blocking this protein may inhibit cancer cells migration and tumor progression. Antibody therapy directed against L1CAM in mice models of cancer block tumor growth but enhance EMT. Liposome- encapsulated small interfering RNA has also proved to be an effective inhibitor for L1CAM expression as its function is to degrade a specific range of mRNA base pairs (in this case, the ones encoding for L1CAM sequence of amino acids) after transcription, so that the protein cannot be synthetised. Nevertheless, these possible therapies involving L1CAM as a target in human cancer are still in preclinical research.
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The bilayer that is formed allows the molecule to fully encapsulate any drug, protecting it while it is travelling through the body. One drawback to shielding the drug from the outside cells is that it no longer has specificity, and requires coupling to extra antibodies to be able to target a biological site. Due to their low stability, liposome- based nanoparticles for drug delivery have a short shelf life. Targeted therapy using magnetic nanoparticles (MNPs) is also a popular topic of research and has led to several stage III clinical trials. Invasiveness is not an issue here because a magnetic force can be applied from the outside of a patient’s body to interact and direct the MNPs.
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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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Journal of Physical Chemistry B (2008), 112(35), 10841-10847 where the backbone block is hydrophilic and the comb branches are hydrophobic, and dendronized block copolymers,Yi, Zhuo; Liu, Xuanbo; Jiao, Qing; Chen, Erqiang; Chen, Yongming; Xi, Fu. Journal of Polymer Science, Part A: Polymer Chemistry (2008), '46'(12), 4205-4217 where the dendrimer portion is hydrophilic. In the case of diblock, comb and dendronized copolymers the polymersome membrane has the same bilayer morphology of a liposome, with the hydrophobic blocks of the two layers facing each other in the interior of the membrane. In the case of triblock copolymers the membrane is a monolayer that mimics a bilayer, the central block filling the role of the two facing hydrophobic blocks of a bilayer.
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Following this finding, Auguste and her team sought to determine an improved way of identifying and targeting triple negative breast cancer (TNBC) cells that did not rely on just one cellular marker. They instead looked at the ratio of ICAM-1 to another marker of TNBC, epithelial growth factor (EGFR), in order to design a therapeutic with the ability to bind multiple ligands at once to selectively target and identify TNBC cells. The complementary targeting of specific ligand ratios was enabled with a dual complementary liposome that specifically binds the ratio of EGFR and ICAM-1 on tumor cells. They showed that binding was effective and also that binding decreased receptor signalling and was able to interfere enough with cellular processes that it could minimize metastasis.
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Tekmira caught the world's attention and its stock rose dramatically during the 2013 West African Ebola virus epidemic due to its drug candidate for Ebola fever, TKM-Ebola. Tekmira was developing it under a $140 million US Department of Defense contract. While its stock was trading high in January 2015, it acquired OnCore BioPharma, a company focused on hepatitis B. Development of TKM-Ebola was terminated in mid June 2015 during a Phase II trial, for lack of efficacy. The next month, Tekmira changed its name to Arbutus Biopharma and said that it would focus on drugs to treat hepatitis B. In March 2017 Arbutus signed another license for its liposome delivery technology, this time with Alexion Pharmaceuticals, for delivery of an mRNA drug candidate.
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Section two establishes various definitions, including section 2(3)(a) which strictly defines "genetically engineered" by specific genetic engineering techniques, and differentiated from selective breeding. These specific genetic engineering techniques include various recombinant DNA and RNA methods such as micro- injection, electroporation, micro-encapsulation, liposome fusion, protoplast fusion or other "hybridization techniques that overcome natural physiological, reproductive or recombination barriers, where the donor cells or protoplasts do not fall within the same taxonomic family, in a way that does not occur by natural multiplication or natural recombination." Section three requires that "any food offered for retail sale" be labeled "clearly and conspicuously" if it contains genetically-engineered ingredients, with certain exceptions. Exemptions consistent with current federal regulations include prepared foods such as those coming from a restaurant, meat from animals fed genetically engineered feeds, alcoholic beverages and foods processed with GE enzymes.
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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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The three main structures phospholipids form in solution; the liposome (a closed bilayer), the micelle and the bilayer. In 1954 and 1958 Krishna Bahadur and co-workers published the successful synthesis of amino acids from a mixture of paraformaldehyde, colloidal molybdenum oxide or potassium nitrate and ferric chloride under sunlight. It appears that this experimental approach was seminal for the assays to produce Jeewanu, which he first reported in 1963 in an obscure Indian journal, Vijnana Parishad Anusandhan Patrika. His detailed syntheses were published in Germany in 1964 in a series of articles. Their initial experiment consisted of a sterilised apparatus in which inorganic nitrogenous compounds (such as ammonium phosphate and ammonium molybdate) and organic compounds such as citric acid (C6H8O7), paraformaldehyde (OH(CH2O)nH) and formaldehyde (CH2O) for carbon sources were mixed with minerals commonly found in living cells.
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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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Prabhakar Misra has been involved in basic and applied spectroscopic research that spans more than 25 years in the field of atomic and molecular physics and condensed matter physics. He has contributed extensively to the understanding of unstable and stable molecular species, which has included among others free radicals and ions that impact combustion and plasma processes. The utilization of the twin techniques of supersonic jet spectroscopy and optogalvanic spectroscopy has enabled the precise spectroscopic characterization of moderate-size organic species and the plasma associated with hollow cathode discharges. Besides the investigation of free radicals, neutral and ionic species in the ultraviolet and visible regions of the electromagnetic spectrum, Dr. Misra's research has also covered a detailed characterization and modeling of adsorption phenomena associated with trace atmospheric species on a variety of metallic and non-metallic surfaces in the mid-infrared region via Fourier Transform infrared spectroscopy and simulation of laser-tissue interactions using a liposome-dye complex.
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It is possible that the exposure of cholesterol at the membrane surface might be facilitated by other membrane- damaging toxins secreted such as phospholipase C, which cleave the head groups of phospholipids increasing the exposure of cholesterol. Two organisms, Clostridium perfringens that produces perfringolysin O (CDC) and α-toxin during clostridial myonecrosis and Listeria monocytogenes which releases listeriolysin O (CDC) and phospholipases C leading to the virulence of these bacteria. However, although the C. perfringens α-toxin treatment of liposome membranes increase the activity of PFO on those membranes this affect does not appear to aways be the case "in vivo". During C. perfringens gas gangrene (myonecrosis) the main site of action of the C. perfringens α-toxin is the muscle tissue, where the cleavage of the phospholipid head groups does not seem to increase the activity of perfringolysin O on this tissue, as knockouts of PFO do not appear to significantly alter the course of the myonecrosis.
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