Clinical Applications of Liposomes
Using liposomes as drug delivery carriers was first proposed by AlecBangham in 1961. In the early 1970s, liposomes have been an indispensable part of nanomedicine research and clinical applications. Liposomes are composed of phospholipids. Phospholipids are composed of a hydrophilic head and a lipophilic tail. Due to van der Waals forces, they form a lipid bilayer sphere. The outer part of the liposome is the hydrophilic part, the inside is the water core, and the middle is sandwiched. It is the lipophilic part. Hydrophilic drugs can exist in the water core, while fat-soluble drugs can appear in a lipid sandwich composed of phospholipid tails. The use of liposomes as drug carriers has two important advantages: good biocompatibility and biodegradability, which are also the most important characteristics of liposomes. In addition, liposomes can also increase the solubility of carrier drugs. To reduce the toxicity of drugs, modified liposomes can also be targeted.
The initially developed liposomes have a short half-life and poor stability in blood circulation, and their application is limited. After years of development, liposomes modified with polyethylene glycol 2000 (PEG) have attracted attention. As the surface of liposomes modified by PEG has increased hydrophilicity and reduced its affinity with phagocytes, it can It avoids the recognition of the reticuloendothelial system and reduces the capture of liposomes, so it is also called invisible liposomes. Stealth liposomes have many advantages. They can reduce the occurrence of immunogenicity and antigenicity. This has a wide range of applications in the development of macromolecular drugs that are prone to immune response; it also affects the physical and chemical properties of drugs and reduces liver clearance rate and prolong the half-life of the drug, thereby reducing the patient's application dose and frequency of use; at the same time, reducing the adverse drug reaction while ensuring the efficacy of the drug.
A well-known example of the application of this technology is Doxil®, which was developed by Sequus, the first liposomal drug approved by the US FDA and the first nano-drug. Compared with Doxil, Doxil's drug distribution volume is much lower; Doxil's clearance rate is 0.1L/h, while Doxil is 45L/h, Doxil's half-life is greatly prolonged; Doxil has lipids The isolation of the body shell makes adriamycin difficult to be absorbed by myocardial cells, thereby reducing cardiotoxicity.
- Non-PEG liposome
Although PEG liposomes have excellent properties, with the deepening of research, the liposomes have also exposed many problems. The main problems are as follows: 1. Because PEG has long fatty chains, it hinders The uptake of liposomes by target cells, and the connection of PEG to liposomes is very stable, making it difficult to degrade; 2. PEG will prevent the fusion of pH-sensitive liposomes (PSL) carrying genes and protein drugs with lysosomes , Making it difficult to exert the drug effect; 3. Repeated injection of PEG liposomes will induce accelerated blood clearance, thereby reducing the therapeutic effect. In order to solve the above problems, people have developed non-PEG liposome technology.
Non-PEG liposome technology is just a general term, and the content of this technology is very extensive. This liposome does not contain PEG components, but it can have similar or better effects than PEG liposomes. At present, the more mature non-PEG liposome is Myocet®, developed by Elan Pharmaceuticals. The liposome is composed of lecithindylcholine (EPC), cholesterol and an aqueous core, and carries doxorubicin for treatment Breast cancer and other diseases.
- DepoFoam liposome
DepoFoam liposome technology was developed by Pacira Pharmaceuticals. As a sustained-release drug delivery system, it is the core technology of many listed drugs. DepoFoam is a multivesicular liposome, which is composed of multiple tiny spherical particles. The inside of the particles is composed of an aqueous cavity, which encapsulates the drug inside and releases it within a desired time. Each chamber is separated from the adjacent chamber by a lipid membrane, which gives DepoFoam a football-like shape. This technology has been developed for more than ten years, and there is a mature process to meet the preparation requirements of a variety of drugs. It can not only be used to deliver small molecules, but also can be used for polypeptides, proteins, antisense oligonucleotides, DNA, etc. A drug that is difficult to deliver with ordinary liposomes.
Exparel is a drug produced by DepoFoam liposome technology. It is a bupivacaine liposome injection used to control surgical pain and reduce or eliminate postoperative local pain. Compared with bupivacaine hydrochloride injection, Exparel reduces pain by 13.6% and reduces the use of opioids by 78%.
- Hemolytic Thermosensitive Liposome (LTSL)
Tumor tissues have enhancement and retention effects, and liposomes can be selectively accumulated in the tumor area. At normal body temperature, the liposome membrane is in a dense colloidal state, so the drug embedded in it is difficult to diffuse. When the target tissue is heated to 40°C or higher, the liposome membrane transitions from the colloidal state to the liquid crystal state, the fluidity of the membrane increases, and the permeability to water and drugs doubles. The loaded drug rapidly diffuses into the target organ, forming a higher drug concentration at the target site.
ThermoDox is a drug produced using this technology and is currently in clinical III research. Compared with doxorubicin, the concentration of the drug in tumors is 25 times that of doxorubicin and 5 times that of ordinary liposomes carrying doxorubicin, which significantly increases the concentration of the drug in tumors. Reduced adverse drug reactions. In terms of therapeutic effects, ThermoDox improved the overall survival (OS) of patients by 2.1 years.
Summary
As a drug delivery system developed in recent years, liposomes are not only widely used in the field of small molecules, but are also popular delivery methods for peptides, proteins, DNA and other drugs, which solves the difficulty in delivering large molecule drugs and nucleic acid drugs in the body. , The difficulty of reaching the target tissue smoothly. Since liposomes have the advantages of good degradability and tolerance, as well as advantages that traditional medicines do not possess, it is believed that more liposomes will enter clinical applications in the future.
About BOC Sciences
BOC Sciences provides comprehensive liposome related products and services, including formulation development, feasibility studies, active molecules encapsulation, custom liposomes, product characterization, and process development and scale-up.
BOC Sciences provides a wide range of liposome products, including cationic liposomes, anionic liposomes, fluorescently labeled liposomes, clodronate liposomes, ATP liposomes, etc., as well as a variety of high-quality liposome preparation materials.
Years of successful operations in the liposome industry have enabled the company to have a mature and fully functional liposome technology platform.
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