liposome, microscopic, fluid-filled pouch whose walls are made of layers of phospholipids identical to the phospholipids that make up cell membranes. Liposomes are used to deliver certain vaccines, enzymes, or drugs (e.g., insulin and some cancer drugs) to the body. When used in the delivery of certain cancer drugs, liposomes help to shield healthy cells from the drugs' toxicity and prevent their concentration in vulnerable tissues (e.g., the kidneys, and liver), lessening or eliminating the common side effects of nausea, fatigue, and hair loss. Liposomes are especially effective in treating diseases that affect the phagocytes of the immune system because they tend to accumulate in the phagocytes, which recognize them as foreign invaders. They have also been used experimentally to carry normal genes into a cell in order to replace defective, disease-causing genes (see gene therapy). Liposomes are sometimes used in cosmetics because of their moisturizing qualities.

Liposomes were first produced in England in 1961 by Alec D. Bangham, who was studying phospholipids and blood clotting. It was found that phospholipids combined with water immediately formed a sphere because one end of each molecule is water soluble, while the opposite end is water insoluble. Water-soluble medications added to the water were trapped inside the aggregation of the hydrophobic ends; fat-soluble medications were incorporated into the phospholipid layer.

In some cases liposomes attach to cellular membranes and appear to fuse with them, releasing their contents into the cell. Sometimes they are taken up by the cell, and their phospholipids are incorporated into the cell membrane while the drug trapped inside is released. In the case of phagocytic cells, the liposomes are taken up, the phospholipid walls are acted upon by organelles called lysosomes, and the medication is released. Liposomal delivery systems are still largely experimental; the precise mechanisms of their action in the body are under study, as are ways in which to target them to specific diseased tissues.

A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases.

Membranes are usually made of phospholipids, which are molecules that have a head and a tail. The head is attracted to water, and the tail, which is made of oil (hydrocarbon), is repelled by water.

In nature, phospholipids are found in stable membranes composed of two layers (a bilayer). In the presence of water, the heads are attracted to water and line up to form a surface facing the water. The tails are repelled by water, and line up to form a surface away from the water. In a cell, one layer of heads faces outside of the cell, attracted to the water in the environment. Another layer of heads faces inside the cell, attraced by the water inside the cell. The hydrocarbon tails of one layer face the hydrocarbon tails of the other layer, and the combined structure forms a bilayer.

When membrane phospholipids are disrupted, they can reassemble themselves into tiny spheres, smaller than a normal cell, either as bilayers or monolayers. These are liposomes.

The lipids in the plasma membrane are chiefly phospholipids like phosphatidyl ethanolamine and cholesterol. Phospholipids are amphiphilic with the hydrocarbon tail of the molecule being hydrophobic; its polar head hydrophilic. As the plasma membrane faces watery solutions on both sides, its phospholipids accommodate this by forming a phospholipid bilayer with the hydrophobic tails facing each other.

Liposomes can be composed of naturally-derived phospholipids with mixed lipid chains (like egg phosphatidylethanolamine), or of pure surfactant components like DOPE (dioleoylphosphatidylethanolamine). Liposomes, usually but not by definition, contain a core of aqueous solution; lipid spheres that contain no aqueous material are called micelles, however, reverse micelles can be made to encompass an aqueous environment.

Etymology

The name liposome is derived from two Greek words: 'Lipid' meaning fat and 'Soma' meaning body. A liposome can be formed at a variety of sizes as uni-lamellar or multi-lamellar construction, and its name relates to its structural building blocks, phospholipids, and not to its size. In contrast, the term Nanosome does relate to size and was coined in the early 1990s to denote special liposomes in the low nanometer range; liposome and Nanosome are not synonyms. A liposome does not necessarily have lipophobic contents, such as water, although it usually does.

Discovery

Liposomes were first described by British haematologist Dr Alec D Bangham FRS in 1961 (published 1964), at the Babraham institute, 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 real evidence for the cell membrane being a bilayer lipid structure.

Application

Liposomes are used for drug delivery due to their unique properties. A liposome encapsulates a region on aqueous solution inside a hydrophobic membrane; dissolved hydrophilic solutes cannot readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to sites of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents. By making 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.

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.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. 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. 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.

Targeting cancer

Another interesting property of liposomes are their natural ability to target cancer. The endothelial wall of all healthy human blood vessels are encapsulated by endothelial cells that are bound together by tight junctions. These tight junctions stop any large particle in the blood from leaking out of the vessel. Tumour vessels do not contain the same level of seal between cells and are diagnostically leaky. This ability is known as the Enhanced Permeability and Retention effect. Liposomes of certain sizes, typically less than 400nm, can rapidly enter tumour sites from the blood, but are kept in the bloodstream by the endothelial wall in healthy tissue vasculature. Anti-cancer drugs such as Doxorubicin (Doxil), Camptothecin and Daunorubicin (Daunoxome) are currently being marketed in liposome delivery systems.

Manufacturing

Liposomes can be created by sonicating phospholipids in water. Low shear rates create multilamellar liposomes, which have many layers like an onion. Continued high-shear sonication tends to form smaller unilamellar liposomes. In this technique, the liposome contents are the same as the contents of the aqueous phase. Sonication is generally considered a "gross" method of preparation, and newer methods such as extrusion are employed to produce materials for human use.

Prospect

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", 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 in order 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. Targeted liposomes can target nearly any cell type in the body and deliver drugs that would naturally be systemically delivered. Naturally toxic drugs can be much less toxic if delivered only to diseased tissues. Polymersomes, morphologically related to liposomes can also be used this way.

References

External links

• International Liposome Society
• Controlled Release Society