The Basic Composition of Liposomes-Cholesterol, Antioxidants and Surfactants
In addition to phospholipids, the basic composition of liposomes includes cholesterol, antioxidants and surfactants.
Cholesterol (Chol) is a commonly used lipid for preparing liposomes, which can increase the rigidity of the lipid membrane and the stability of the liposome. Cholesterol is an amphiphilic molecule with a hydroxyl polar head, and the hydrophobic part is composed of four rigid steric rings in a planar configuration connected by a flexible short hydrocarbon chain. The structure of soy sterol is similar to that of cholesterol, and it can also be used for the construction of liposomes, and its membrane stability function is also similar to that of cholesterol.
The liposome bilayer is generally composed of phospholipids and cholesterol molecules which are spaced apart and arranged in an orientation. When cholesterol is embedded in the lipid bilayer, the hydrophobic part is sandwiched between the “barriers” of the lipid bilayer, the hydroxyl head is in the polar region, and hydrogen bonds with the carbonyl group of the lipid acyl chain of the phospholipid, which reduces the molecular mobility of the bilayer, can adjust the fluidity and permeability of the bilayer. The increase of cholesterol content makes the liposome membrane phase become blurred and becomes stable, but when the cholesterol is lower than the phospholipid phase transition temperature, it will have a fluidizing effect. It will increase the membrane fluidity.
When using liposomes as drug carriers, the ratio of phospholipids, cholesterol, and drugs needs to be considered. Because the ratio between them determines many properties of liposomes. Water-soluble drugs are loaded in the aqueous phase of liposomes. In general, the cholesterol ratio does not affect the encapsulation rate or drug loading rate. The fat-soluble drug is contained in the bimolecular membrane of the liposome, which is basically consistent with the position of cholesterol. Therefore, the ratio of cholesterol will affect the drug loading. For the preparation of liposoluble drug liposomes, the ratio of cholesterol needs to be examined in detail to obtain liposome preparations with good stability and high drug loading rate.
Antioxidants
Because liposomes are easily oxidized, this is not conducive to drug delivery and can produce toxic products. Therefore, it is necessary to add a certain amount of antioxidant to the liposome prescription. The addition of antioxidants can inhibit or slow down the oxidation of phospholipids and the production of lysophosphatidylcholine. Commonly used antioxidants are vitamin E (a-tocopherol) and butylhydroxytoluene (BHT). In addition, in the preparation and production of liposomes, in order to ensure that the liposomes are not oxidized, it is often necessary to add nitrogen for protection.
Adding poloxamer, polysorbate 80, Brij and other surfactants to the preparation of liposomes, or PEG derivatives of phospholipids (such as DSPE-PEG) can play a protective role on liposomes. These surfactants are either intercalated into the phospholipid bilayer through fat chains, or adsorbed on the surface of liposomes through hydrogen bonding or electrostatic interaction. Both can form a hydrophilic protective layer on the surface of liposomes. This hydration layer It can not only prevent liposomes from aggregating each other, but also avoid opsonization in the body, prolong the blood circulation time, and obtain long-circulation liposomes.