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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. 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. Around this time he was joined at Babraham by Gerald Weissmann , an American physician with an interest in lysosomes. Now an emeritus professor at New York University School of Medicine, Weissmann recalls the two of them sitting in a Cambridge pub and reflecting on the role of lipid sheets in separating the interior of the cell from the exterior milieu.

This insight, they felt, was to cell function what the discovery of the double helix had been to genetics. It was Weissmann who proposed the more user-friendly term liposome. 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. 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.

Liposomes are used as models for artificial cells. Liposomes can also be designed to deliver drugs in other ways. Liposomes that contain low or high pH can be constructed such that dissolved aqueous drugs will be charged in solution i. 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. 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.

Liposomes can be made in a particular size range that makes them viable targets for natural macrophage phagocytosis. 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.

Advance and Perspective in Medical Application of Liposomes

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, [17] pesticides to plants, enzymes and nutritional supplements to foods, and cosmetics to the skin. Liposomes are also used as outer shells of some microbubble contrast agents used in contrast-enhanced ultrasound.

Regarding the use of liposomes as a carrier of dietary and nutritional supplements; until very recently the use of liposomes were primarily directed at targeted drug delivery. However, the versatile abilities of liposomes are now being discovered in other settings.

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Liposomes are presently being implemented for the specific oral delivery of certain dietary and nutritional supplements. A very small number of dietary and nutritional supplement companies are currently pioneering the benefits of this unique science towards this new application.

This new direction and employment of liposome science 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. It is important to note that certain influential factors have far-reaching effects on the percentage of liposome that are yielded in manufacturing.

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These are very crucial elements which lead to the long term stability of the liposomes. These complex yet significant factors 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 primary and key elements comprise the foundation of an effective liposome carrier for use in increasing the bioavailability of oral dosages of dietary and nutritional supplements.

The choice of liposome preparation method depends, i. 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. 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 and Mozafari method [26] are employed to produce materials for human use. Using lipids other than phosphatidylcholine can greatly facilitate liposome preparation. 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 ".

Liposome - Wikipedia

They were first proposed by G. Cevc and G. Blume [27] and, independently and soon thereafter, the groups of L. Huang and V. Torchilin [28] 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.

However, research currently seeks to investigate at what amount of PEG coating the PEG actually hinders binding of the liposome to the delivery site. 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. 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. The typical characteristic of bilayer-forming lipids is their amphiphilic nature: a polar headgroup covalently attached to one or two hydrophobic hydrocarbon tails. Structures of the most commonly used bilayer-forming lipids are illustrated in Table 1.

When these lipids are exposed to an aqueous environment, interactions between themselves hydrophilic interactions between polar headgroups and Van der Waals' interactions between hydrocarbon chains and with water hydrophilic interactions, hydrophobic effect lead to spontaneous formation of closed bilayers. They can also differ in terms of lipid composition and structural organization, corresponding to uni-, oligo- or multi-lamellar vesicles.

Liposomes are built in such a way that the solute can be encapsulated in the aqueous compartment polar solutes or embedded in the lipid bilayers lipophilic or amphiphilic solutes. The properties of liposomes and their subsequent applicability depend on the physical and physico-chemical characteristics of the liposomal membrane.

Medical Applications of Liposomes

Usually, a zwitterionic or non-ionic lipid is used as the basic lipid for the preparation of liposomes Table 1. The net surface charge of liposomes can be modified by the incorporation of positively charged lipids, such as stearylamine, or negatively charged lipids, such as dicetylphosphate, phosphatidyl glycerol Table 1 or phosphatidyl serine.

Bilayer elasticity is related to elastic properties such as tensile strength, compressibility and bending.

Liposome Basics-Part two

This property has been used to understand the response of bilayers to mechanical stress and to manufacture liposomes. The fluidity of the liposomal bilayer, when it is made from a single lipid, depends on the lipid phase transition temperature Tc and its relative position compared to ambient temperature.

When ambient temperature is increased and reaches Tc, the membrane passes from a "solid" gel phase, where the lipid hydrocarbon chains are in an ordered state, to a "fluid" liquid-crystal phase, a disordered state, where molecules have more freedom of movement 2. Hence, depending on lipid Tc Table 1 , different membranes composed of distinct lipids can exhibit different fluidity levels at the same temperature.

The bilayer permeability is a measure of the flux or rate at which a solute works its way from an aqueous compartment, through a bilayer, and out into the aqueous compartment on the other side. It depends on the membrane fluidity and on the nature of the solute. Membrane permeability is highest at the phase transition temperature, and is lower in the gel phase than in the fluid phase.

The fusion properties of liposomal membranes have recently gained special attention with the discovery of lipid compositions that allow for the delivery of macromolecules into the cytoplasm of cells 9, Membrane fusion is promoted by bilayer dehydration 11 , by acidification when the membrane contains pH-sensitive lipids, such as DOPE 12 , and by the presence of cationic lipids or of anionic lipids with divalent cations.

Since the early s, many hundreds of drugs, including antitumor and antimicrobial agents, chelating agents, peptide hormones, enzymes, other proteins, vaccines and genetic materials, have been incorporated into the aqueous or lipid phase of liposomes of various sizes, compositions and other characteristics by an ever increasing number of technologies The successful evolution of liposomes from experimental tools to industrially manufactured products for clinical and veterinary use depends on efficient drug entrapment using simple, reproducible and inert methods.

In the case of an antigenic protein or peptide, such association may be obtained by covalent attachment of the antigen to the liposome surface 14 , or take the form of entrapment into the aqueous phase of vesicles, adsorption onto their surface, or partition into the bilayers 2. Among available methods for peptide or protein encapsulation, three are outstanding for higher encapsulating efficiency.

Preparation of reverse-phase evaporation vesicles REV consists of a rapid injection of aqueous solution into an organic solvent which contains the lipids dissolved. The next step is to subject the gel to vigorous mechanical shaking to induce a phase change from a water-in-oil emulsion to a vesicle suspension.

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In these circumstances, some water droplets collapse, and these droplets attach to adjacent, intact vesicles to form the outer leaflet of the bilayer of a large unilamellar liposome diameter in the range of 0. Preparation of DRV consists of mixing an aqueous solution of the solute with a suspension of 'empty' water-containing liposomes and freeze-drying the resulting mixture.

The intimate contact of flattened liposomal membrane structures and solute molecules in a dry environment and the fusion of membranes caused by dehydration facilitates the incorporation of solute during the controlled rehydration steps. Separation of solute-containing DRV from unentrapped solute can be carried out easily if needed by centrifugation, for example. Vesicles formed by the dehydration-rehydration technique are multilamellar with heterogeneous sizes diameters varying from 0.

The third method requires the use of detergent Lipids are first solubilized with an aqueous solution of the detergent that also contains the protein s to be encapsulated. The detergent should have a high critical micelle concentration CMC so that it is easily removed, for instance by dialysis. During detergent removal, relatively small liposomes mean diameter in the range of 0. This latter method was found to be particularly suitable for the reconstitution of membrane proteins in liposomes.

The most important use of liposomes results from their ability to retain solutes for long periods of time.