Liposome

A liposome (Greek lipos, fat ' and soma, body ', plural: liposomes) is a bubbles ( vesicles), which includes an aqueous phase and the membrane envelope consists of a double layer of molecules that both a non-polar ( lipophilic, fat- loving) as well as a polar ( hydrophilic, water loving) have part and thus referred to as amphiphilic. Mostly it is in the membrane-forming molecules to substances from the class of lipids, such as phospholipids and fatty acids. Liposomes serve as a model for studying the biophysical properties of biomembranes and see beyond the cosmetic, and especially in the medical field ( drug targeting ) application. Liposomes are to be distinguished from the micelles, which only have a single lipid layer.

Discovery

Discovered and described liposomes for the first time in 1964 by a research group at the Babraham Institute around the British hematologists Alec Douglas Bangham. The term " liposome" is due to Gerald Weissmann, who was also instrumental in the discovery and exploration of liposomes. The in 1964 by Alec Douglas Bangham and RW Horne published in the Journal of Molecular Biology publication " Negative staining of phospholipids and Their structural modification by surface- active agents as -observed in the electron microscope " is considered to be the publication in which liposomes (then called " multilamellar smectic mesophases ") is first mentioned.

Structure and properties

The membrane-forming molecules of a liposome have a hydrophilic / lipophobic, as well as a hydrophobic / lipophilic part. In the formation of the bilayer of the liposome, these amphiphilic molecules are arranged according to these properties. The hydrophobic portions of the molecules are directed towards each other, so that they have little contact with the aqueous phase, whereas the hydrophilic parts of the molecules are directed towards the aqueous phase inside and outside of the liposome. The formation of an energetically favorable spherical shape with the smallest possible surface area is based on this behavior ( hydrophobic effect). The molecules of the membrane hold together by non-covalent interaction. This results in a fluid membrane having aliphatic lipophilic interior of which is susceptible to the inclusion of a variety of lipophilic substances.

Size and form of liposomes are fundamentally dependent on the chemical composition of the lipid membrane, the physical and chemical properties of the aqueous phase (for example, ionic strength, pH, osmolality ) in which they are present or which it encloses, and the preparation methods ( see Preparation ). Liposomes may be a single layer ( a bilayer unilamellar ) or several layers (several concentric bilayers, multilamellar ) and must have an average diameter of 25 nm to 100 microns. These two parameters, size (mean diameter ) and lamellarity can be roughly divided into four categories liposomes.

Multilamellar vesicles (MLV ) are generally composed of several concentric lipid bilayers. Their average diameter is between 100 nm and 1000 nm Small unilamellar vesicles (SUV) are unilamellar and have an average diameter between 25 nm and 100 nm, whereas large unilamellar vesicles ( LUV ) and giant unilamellar vesicles (GUV ) having a mean diameter in the range from 1000 nm or between 1 micron and 100 microns. The larger liposomes are, therefore, to detect light in the visible with a light microscope.

The membrane of a liposome can be composed of various lipids. Depending on the desired pharmacodynamic profile of action, pharmacokinetic behavior, chemical and physical properties such as size, size distribution, lamellarity, fluidity, permeability, zeta potential, phase transition temperature of the membrane, etc. can be selected for the preparation of liposomes for medical and cosmetic applications from a wide range variety of lipids from the classes of phospholipids and sterols. The lipids of these two classes of compounds are structuring primarily components of the liposome. In addition, lipopolysaccharide ( eg lipid A as an adjuvant ) come, fatty acids and other lipophilic substances, such as Tocopherols ( antioxidant ) and squalene as membrane components are used.

The first stage of development to living cells in the primordial soup were probably liposome-like structures that have ( for example, phosphatidylcholine lecithin) spontaneously formed from amphiphilic lipids in an aqueous medium.

Applications

The liposomal formulation of drugs, it is possible to protect sensitive drugs by the application of a potential metabolism. Similarly, niosomes are used. Also can be increased by the inclusion of drugs in liposomes, the plasma half-life. Liposomes as drug delivery system provide for a targeted and selective transport of drugs to those places in the body where they are needed. Characterized side effect of liposomally formulated drug is reduced and, as lower dosages may be administered, increasing the efficiency and therapeutic index. A liposomal formulation is due to the properties of the liposome open most drugs. Hydrophilic drugs are enclosed and are located in the hydrophilic interior of the liposome. Lipophilic medicinal substances are embedded in the membrane and amphiphilic drugs at the interface between the membrane and the interior of the aqueous phase. Liposomal formulations of drugs, such as biopharmaceuticals, including, among other vaccines, as well as siRNA and miRNA for use in the therapeutic RNA interference, but also by nonbiological synthetic drugs bring pharmacological and economic advantages. Virosomes, ie liposomes, which carry viral envelope proteins in their lipid membrane, serve as a system for a targeted and selective transport and as an adjuvant. Virosomes that are incorporated into cells after endocytosis by the endosomal membrane, also have the property of both a humoral immune response and to elicit a cellular immune response.

In some pharmaceutical products, the liposomes need to be protected by a surface layer polymer (typically polyethylene glycol ) in order to avoid a fusion with a random, arbitrary cell membrane (typically in the liver), before the active substance has arrived at its destination. On the way to their destination the enclosed in a liposome agents can be protected by the lipid bilayer against the destructive action of enzymes and premature elimination from the body. With the help of foreign molecules ( such as antibodies ) that are attached to the outside of the liposomes can also try to set the destination of the drug by binding to a specific receptor accurate ( drug targeting ). Because of their similar chemical nature of the cell membrane liposomes can probably easily with the cell membrane or by endocytosis or pinocytosis one, with the endosome and lysosome membrane merge and then released their contents into the cell interior.

In biotechnology, liposomes are occasionally used, for example, plasmids, inject foreign material into a cell. This process is known as a liposomal transfection or lipofection, however, to date only very imperfectly understood and much less effective as a transduction by a viral vector.

As an alternative to liposomes and polymersomes are used.

Production

Multilamellar liposomes ( MLV) arise spontaneously by dissolving lipids in aqueous phase. Unilamellar liposomes ( SUV / LUV ) can be generated by different methods.

Liposomal finished product

By 2008, 11 drugs were approved in liposomal administration.

The importance of liposomal drug formulations for drug targeting in particular for diseases such as cancer or infections in cystic fibrosis is seen in a significant number of corresponding formulations orphan drugs.