Liposome
A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes.
Liposomes are most often composed of phospholipids, especially phosphatidylcholine, and cholesterol, but may also include other lipids, such as those found in egg and phosphatidylethanolamine, as long as they are compatible with lipid bilayer structure. A liposome design may employ surface ligands for attaching to desired cells or tissues.
Based on vesicle structure, there are seven main categories for liposomes: multilamellar large, oligolamellar, small unilamellar, medium-sized unilamellar, large unilamellar, giant unilamellar and multivesicular vesicles. The major types of liposomes are the multilamellar vesicle, the small unilamellar liposome vesicle, the large unilamellar vesicle, and the cochleate vesicle. A less desirable form is multivesicular liposomes in which one vesicle contains one or more smaller vesicles.
Liposomes should not be confused with lysosomes, or with micelles and reverse micelles. In contrast to liposomes, micelles typically contain a monolayer of fatty acids or surfactants.
Discovery
The word liposome derives from two Greek words: lipo and soma ; it is so named because its composition is primarily of phospholipid.Liposomes were first described by British hematologist Alec Douglas Bangham in 1961 at the Babraham Institute, in Cambridge—findings that were published 1964. The discovery came about 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 microscopic pictures provided the first evidence that the cell membrane is a bilayer lipid structure. The following year, Bangham, his colleague Malcolm Standish, and Gerald Weissmann, an American physician, established the integrity of this closed, bilayer structure and its ability to release its contents following detergent treatment. During a Cambridge pub discussion with Bangham, Weissmann first named the structures "liposomes" after something which laboratory had been studying, the lysosome: a simple organelle whose structure-linked latency could be disrupted by detergents and streptolysins. Liposomes are readily distinguishable from micelles and hexagonal lipid phases through negative staining transmission electron microscopy.
Bangham, with colleagues Jeff Watkins and Standish, wrote the 1965 paper that effectively launched what would become the liposome "industry." Around that same time, Weissmann joined Bangham at the Babraham. Later, Weissmann, then an emeritus professor at New York University School of Medicine, recalled the two of them sitting in a Cambridge pub, reflecting on the role of lipid sheets in separating the cell interior from its exterior milieu. This insight, they felt, would be to cell function what the discovery of the double helix had been to genetics. As Bangham had been calling his lipid structures "multilamellar smectic mesophases," or sometimes "Banghasomes," Weissmann proposed the more user-friendly term liposome.
Mechanism
Encapsulation in liposomes
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. This property can be utilized to load liposomes with hydrophobic and/or hydrophilic molecules, a process known as encapsulation. Typically, liposomes are prepared in a solution containing the compound to be trapped, which can either be an aqueous solution for encapsulating hydrophilic compounds like proteins, or solutions in organic solvents mixed with lipids for encapsulating hydrophobic molecules.Encapsulation techniques can be categorized into two types: passive, which relies on the stochastic trapping of molecules during liposome formation, and active, which relies on the presence of charged lipids or transmembrane ion gradients.
A crucial parameter to consider is the "encapsulation efficiency," which is defined as the amount of compound present in the liposome solution divided by the total initial amount of compound used during the preparation.
In more recent developments, the application of liposomes in single-molecule experiments has introduced the concept of "single entity encapsulation efficiency." This term refers to the probability of a specific liposome containing the required number of copies of the compound.
Delivery
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, that does not apply to nutrients and drug delivery. By preparing liposomes in a solution of DNA or drugs they can be delivered past the lipid bilayer. Liposomes can also be designed to deliver drugs in other ways. Liposomes that contain low pH can be constructed such that dissolved aqueous drugs will be charged in solution. As the pH naturally neutralizes within the liposome, 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. However, the efficacy of this pH regulated passage depends on the physiochemical nature of the drug in question, which is very low for many drugs.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. 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.
To improve the tolerability of amphotericin and reduce toxicity, researchers developed several lipid formulations. Liposomal formulations have been found to have less renal toxicity than deoxycholate. and fewer infusion-related reactions.
AmBisome is a liposomal formulation of amphotericin B for injection and consists of a mixture of phosphatidylcholine, cholesterol and distearoyl phosphatidylglycerol that in aqueous media spontaneously arrange into unilamellar vesicles that contain amphotericin B. It was developed by NeXstar Pharmaceuticals. It was approved by the FDA in 1997. It is marketed by Gilead in Europe and licensed to Astellas Pharma for marketing in the US, and Sumitomo Pharmaceuticals in Japan.
Regarding pH-sensitive liposomes, there are three mechanisms of drug delivery intracellularly, which occurs via endocytosis. This is possible because of the acidic environment within endosomes. The first mechanism is through the destabilization of the liposome within the endosome, triggering pore formation on the endosomal membrane and allowing diffusion of the liposome and its contents into the cytoplasm. Another is the release of the encapsulated content within the endosome, eventually diffusing out into the cytoplasm through the endosomal membrane. Lastly, the membrane of the liposome and the endosome fuse together, releasing the encapsulated contents onto the cytoplasm and avoiding degradation at the lysosomal level due to minimal contact time.
Certain anticancer drugs such as doxorubicin and daunorubicin may be administered encapsulated in liposomes. Liposomal cisplatin has received orphan drug designation for pancreatic cancer from EMEA. A study provides a promising preclinical demonstration of the effectiveness and ease of preparation of valrubicin-loaded immunoliposomes as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.
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.
Liposomes are also used as outer shells of some microbubble contrast agents used in contrast-enhanced ultrasound.
Dietary and nutritional supplements
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 and small intestines allowing the encapsulated nutrient to be efficiently delivered to the cells and tissues.The term nutraceutical combines the words nutrient and pharmaceutical, originally coined by Stephen DeFelice, who defined nutraceuticals as "food or part of a food that provides medical or health benefits, including the prevention and/or treatment of a disease". However, currently, there is no conclusive definition of nutraceuticals yet, to distinguish them from other food‐derived categories, such as food supplements, herbal products, pre‐ and probiotics, functional foods, and fortified foods. Generally, this term is used to describe any product derived from food sources which is expected to provide health benefits additionally to the nutritional value of daily food. A wide range of nutrients or other substances with nutritional or physiological effects might be present in these products, including vitamins, minerals, amino acids, essential fatty acids, fibres and various plants and herbal extracts. Liposomal nutraceuticals contain bioactive compounds with health-promoting effects. The encapsulation of bioactive compounds in liposomes is attractive as liposomes have been shown to be able to overcome serious hurdles bioactives would otherwise encounter in the gastrointestinal tract upon oral intake.
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: The actual manufacturing method and preparation of the liposomes themselves; The constitution, quality, and type of raw phospholipid used in the formulation and manufacturing of the liposomes; 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.