Introduction

A liposome is an artificial membrane. The hydrophilic head of the phospholipid molecule in water is inserted into the water, and the hydrophobic tail of the liposome extends to the air, and the spherical liposome which forms a double-layered lipid molecule after agitation, ranging from 25 to 1000 nm in diameter. Liposomes can be used for transgenic, or prepared drugs, using the characteristics that liposomes can fuse with cell membranes, and the drugs are fed into the cell.

Biological definition: when amphiphilic molecules such as phospholipids and sphingolipids are dispersed in the aqueous phase, the molecules are hydrophobic. The tails tend to clump together, avoiding the aqueous phase, while the hydrophilic head is exposed to the aqueous phase, forming a closed vesicle with a bilayer structure called a liposome. Definition of Pharmacy Liposomes: Microcapsules formed by encapsulating a drug in a lipid-like bilayer.

Classification

Classification of liposomes

1. Liposomes are classified into single-chamber liposomes and multi-chamber liposomes according to the number of layers of the lipid-like bilayer contained.

Small single-chamber liposome (SUV): particle size of about 0.02-0.08 μm; large single-chamber liposome (LUV) is a single-layer large vesicle with a particle size of 0.1 to 1 μm.

The vesicles of the multi-layer bilayer are called multi-chamber liposomes (MIV) and have a particle size of between 1 and 5 μm.

2. According to the structure: single-chamber liposome, multi-chamber liposome, multivesicular liposome

3. According to charge fraction: neutral liposome, negatively charged liposome, positively charged liposome

4. According to performance points: general liposome, special effect liposome

Composition
Composition and structure of liposomes

Composition of liposomes: lipidoids (phospholipids) and additives.

1. Phospholipids: including natural phospholipids and synthetic phospholipids. The phospholipid is structurally characterized by a hydrophilic group consisting of a phosphate group and a quaternary ammonium salt group, and a lipophilic group composed of two longer hydrocarbon groups.

The natural phospholipid is mainly lecithin (phosphatidylcholine, PC), which is derived from egg yolk and soybean, and is neutral.
Synthetic phospholipids mainly include DPPC (dipalmitoylphosphatidylcholine), DPPE (dipalmitoylphosphatidylethanolamine), DSPC (distearoylphosphatidylcholine), etc., all of which are hydrogenated phospholipids, which are stable in nature and resistant. Strong oxidizing properties, stable products and other characteristics.

2. Cholesterol: Cholesterol and phospholipid are the basic substances that together constitute the cell membrane and liposome. Cholesterol has the function of regulating the fluidity of the membrane, so it can be called a liposome "fluidity buffer".

Quality control

1. Morphology, particle size and distribution
Measured by scanning electron microscopy, laser light scattering or laser scanning. The particle size varies depending on the route of administration.
For example, the particle size of the liposome administered by injection should be less than 200 nm, and the distribution is uniform, normal, and the span should be small.

2. Encapsulation rate and drug loading
Encapsulation efficiency: encapsulation ratio = (encapsulated drug in liposome / total amount of drug in liposome) × 100%
The free drug and the liposome in the solution are generally separated by a separation method such as a glucan gel, an ultracentrifugation method, or a dialysis method, and respectively measured, and the encapsulation efficiency is calculated. The drug encapsulation rate of liposomes is usually required to be more than 80%.

Drug loading: drug loading = [amount of drug in liposome / (total amount of drug + carrier in liposome)] × 100%
The amount of drug loading directly affects the clinical application dose of the drug, so the larger the drug loading, the easier it is to meet the clinical needs. The drug loading is related to the nature of the drug, and usually the lipophilic drug or the hydrophilic drug is relatively easy to be made into a liposome.

3. Liposome stability

1) Physical stability: mainly expressed by leakage rate.
Leakage rate = (the amount of drug in the medium before placement - the amount of drug in the medium after placement) / the amount of drug in the preparation x100%
Cholesterol can strengthen the lipid bilayer membrane, reduce membrane flow, and reduce leakage.
2) Chemical stability:
(1) Phospholipid oxidation index: oxidation index = A233nm / A215nm; generally specified phospholipid oxidation index should be less than 0.2.
(2) Determination of the amount of phospholipids: Based on the fact that only one phosphorus atom is contained in each phospholipid molecule, the phospholipid amount can be derived by chemically converting the phospholipid in the sample to inorganic phosphorus and measuring the molar amount (or weight) of the phosphorus.

4. Measures to prevent oxidation:
The general measures for preventing oxidation include filling with nitrogen, adding an antioxidant-tocopherol, a metal complexing agent, etc.; it is also possible to directly use a hydrogenated saturated phospholipid.

5. Sterilization of liposomes:
The general methods of sterilization include filtration sterilization, aseptic processing, -ray irradiation (60 cobalt 15 to 20 kGy), and autoclaving at 121 °C.

Characteristics

1. Targeting and lymphatic orientation: passive targeting of the liver and spleen reticuloendothelial system. It is used for the prevention and treatment of diseases of mononuclear-macrophage system such as hepatic parasitic diseases and leishmaniasis. For example, the liver leishmania prodrug citrate liposome has a liver concentration that is 200-700 times higher than that of the common preparation.
2. Sustained release: slow release, delay renal excretion and metabolism, thereby prolonging the action time.
3. Reduce drug toxicity: such as amphotericin B liposome can reduce cardiotoxicity.
4. Improve stability: such as insulin liposomes, vaccines, etc. can improve the stability of the main drug.

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