The Preparation of liposomes

Injection method, thin film dispersion method, ultrasonic dispersion method, reverse evaporation method.

Clinical application of liposomes as drug carriers

1. Anti-tumor drug carrier: Adriamycin liposome and cisplatin liposome have been marketed abroad.
2. Antiparasitic drug carrier: Fenthiamidazole liposome and albendazole liposome, etc. Using the passive targeting of liposomes, the bioavailability of the drug is improved, the dosage is reduced, and the toxic and side effects are reduced.
3. Antibacterial drug carrier: gentamicin liposome and amphotericin B, which can reduce drug resistance and reduce cardiotoxicity.
4. Hormone drug carrier.

Route of administration

The routes of administration of liposomes mainly include (1) intravenous injection; (2) intramuscular and subcutaneous injection; (3) oral administration; (4) ocular administration; (5) pulmonary administration; (6) Transdermal administration; (7) Nasal administration.

In vivo processes

The main forms of interaction between liposomes and cells include inter-membrane transport (lipid exchange in cell membranes), contact release, adsorption, fusion, and endocytosis.

Liposomes have a cell-like structure. When entering the body, they are mainly swallowed by the reticuloendothelial system to activate the body's own immune function, and change the distribution of encapsulated drugs in the body, so that the drugs are mainly accumulated in tissues and organs such as liver, spleen, lung and bone marrow. , Thereby improving the therapeutic index of the drug, reducing the therapeutic dose of the drug and reducing the toxicity of the drug.

Novel targeted liposomes

1. Proliposomes: Liposomes are made by adsorbing lipids on very fine water-soluble carriers such as sodium chloride, sorbitol and other polymeric sugars (increasing the lipid dispersion area). Liposomes are made into liposomes when exposed to water. Swelling, the carrier dissolves to form a multilayer liposome, the size of the carrier

It directly affects the size and uniformity of liposomes. Proliposomes can prevent the aggregation of liposomes and are more suitable for encapsulating fat-soluble drugs.

1. Long-circulating liposomes: modified with PEG to increase the flexibility and hydrophilicity of liposomes, phagocytose through the mononuclear-macrophage system, reduce the interaction between liposome lipid membranes and plasma proteins, and prolong circulation Time, called long circulating liposomes

(long-circulating liposome). Long circulating liposomes are beneficial to the targeting of tissues or organs other than the liver and spleen. At the same time, the antibody or ligand is bound to the end of PEG, which can maintain long circulation,

It can maintain the recognition of the target body.

1. Immunoliposomes: antibodies are attached to the surface of liposomes to identify target cells and improve the targeting of liposomes. For example, the mitomycin (MMC) liposome is combined with a monoclonal antibody 3G against the surface antigen of gastric cancer cells to make an immunolipid.

The M85 killing effect of the immunoliposome on gastric cancer target cells in vivo is 4 times higher than that of free MMC.

1. Thermosensitive liposomes: use the principle that the lipid bilayer membrane of liposomes transitions from colloidal to liquid crystal state at the phase transition temperature, the permeability of the lipid membrane increases, and the drug release rate increases. Prepare heat-sensitive liposomes. For example, dipalmitate phospholipid

(DPPC) and distearic acid phospholipid (DSPC) were mixed in a certain proportion to prepare 3H methotrexate heat-sensitive liposomes, and then injected into the tail vein of mice bearing Lewis lung cancer, and then microwaved to heat the tumor site to At 42°C, the radioactive intensity of the lesion site was significantly higher than that of the non-heat-sensitive liposome control group.

1. pH-sensitive liposomes: Since the pH of the tumor interstitium is lower than that of the surrounding normal tissue cells, lipid materials that are sensitive to pH, such as dipalmitic acid phospholipid or heptadecanoic acid phospholipid, are used as the membrane material to prepare the drug Liposomes. When liposomes enter the tumor

At the same time, due to the decrease of pH, the fatty acid carboxyl group is lipidated into a non-phase layer structure of hexagonal crystal phase, so that the membrane is fused and the drug release is accelerated.

In short, liposomes as drug carriers are the earliest and most mature type of new targeted preparations in clinical application. The liposome products approved by the US FDA include amphotericin B and adriamycin liposomes. Lipids approved for clinical trials

The plastid has amikacin. The future research of liposomes will mainly focus on the following three aspects:

1. The relationship between membrane structure and drug loading properties;
2. The targeting properties of liposomes in vivo;
3. The introduction of genes and other substances into cells in in vitro culture is expected to become a gene drug carrier.

Liposomes are particles composed of lipid bilayers, which mediate genes across cell membranes. Liposome-mediated gene transfer has the following obvious advantages than using viral transduction: ①The process of complexing liposomes and genes is easier; ②It is easy to produce in large quantities; ③Liposomes are non-viral vectors, and fusion with cell membranes After the target gene is introduced into the cell, the lipid is degraded, non-toxic and non-immunogenic; ④DNA or RNA can be protected from being inactivated or degraded by nuclease; ⑤The gene carried by the liposome may be transported to a specific site; ⑥ In vitro and in vivo experiments have shown that DNA fragments close to the size of chromosomes can also be transported to the host genome and grow; ⑦ The transfection process is convenient and easy to implement, with good reproducibility.

Liposomes are enclosed particles with a double-layer membrane. The self-aggregating lipid molecules encapsulate the internal water phase medium. They can be divided into large and small multilamellar, oligolamellar and unilamellar liposomes. They are mostly used in medicine. Small unilamellar liposomes. Based on the experience of liposomes as drug carrier systems, liposomes ideal for gene transfer have high encapsulation efficiency for plasmid DNA and protect the DNA from degradation by plasma ribozymes. Their particle size distribution range is narrow, and the particles The average diameter is 100 nm or less. In order to make liposomes close to the extravascular area, lipids with broad binding potential are used. This special lipid can promote fusion with cell membranes and/or improve the stability of liposomes in the circulatory system. The first type is traditional liposomes. People can control their in vitro behavior but cannot control their in vivo behavior. They are quickly inactivated or fixed; the second type is inactive liposomes (that is, they do not interact with the outside world). ), the interaction is inhibited due to the steric stability of the polymer encapsulated on the surface; the third liposome surface binds antigens, lectins or other groups, and can also interact specifically due to the specific ligands bound on the surface ; The fourth type is reactive liposomes, such as ionic, target-sensitive and fusogenic liposomes. This liposome is sometimes referred to as a phase-transition porous liposome. There are ion-sensitive subunits in the liposome, Ca2+ Other metal ion-sensitive liposomes also include cationic liposomes and anionic liposomes. Anionic liposomes do not belong to the reactive category, except for special tests such as the interaction with oppositely charged (multiple) ions in a test tube.

Conventional liposomes enter cells to transport DNA experiments. The principle is that liposomes enhance the aggregation of cell bodies, that is, accelerate the penetration of large molecules and highly charged molecules through the membrane. The process is quite complicated, especially when encapsulating larger fragments. In practice, this technique is only used in vitro and a fusion agent is used. The more charged, the less useful it is.

About us

BOC Sciences provides a wide range of liposome products, including: anionic liposomes, clodronate, cationic liposomes, liposome fluorescence dye, etc., as well as a variety of high-quality liposome preparation materials.