acridine orange. Method of
fluorescence microscopy (1250-fold magnification). (1000-fold magnification). The following types of liposomes are visible: small monolamellar vesicles, large monolamellar vesicles, multilamellar vesicles, oligolamellar vesicles.
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. 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 (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. However, the efficacy of this pH regulated passage depends on the physiochemical nature of the drug in question (e.g. pKa and having a basic or acid nature), 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 (liposomal amphotericin B; LAMB) 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 (acquired by
Gilead Sciences in 1999). It was approved by the FDA in 1997. It is marketed by Gilead in Europe and licensed to
Astellas Pharma (formerly Fujisawa Pharmaceuticals) for marketing in the US, and
Sumitomo Pharmaceuticals in Japan.[56][57][58] 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. A study provides a promising preclinical demonstration of the effectiveness and ease of preparation of
valrubicin-loaded immunoliposomes (Val-ILs) 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==