An important feature that distinguishes liposomes from other common preparations is their targeting nature. The targeting properties of liposomes are divided into passive targeting and active targeting. Passive targeting is the natural distribution of liposomes after entering the human body, that is, liposomes injected intravenously are mainly located in the liver, spleen, and bone marrow. , macrophages in the blood, etc.; active targeting is to change the passive targeting characteristics of liposomes so that they can be localized to specific cells, tissues, and organs. This is affected by the size of liposome particles and the type of capillaries. restrictions. The targeting of liposomes can be verified by radioactive element labeling or high-performance liquid chromatography analysis.
The target of the liposomes can be adjusted by changing the administration method, administration site and particle size of the liposomes. In addition, certain recognition molecules can also be connected to the liposomes to achieve specific targeting through their specific binding to target cells.
Targeting is the most prominent advantage of liposomes as drug carriers. After liposomes enter the body, they are mainly phagocytosed by the reticuloendothelial system, so that the carried drugs are transported to the liver, spleen, and lungs. It accumulates in tissues and organs rich in phagocytes such as bone marrow and bone marrow. Positive liposome (cationic liposome) is also called cationic liposome. Positively charged liposome (Positively charged liposome) is a kind of lipid vesicle with positive charge itself.
⒊1.1 Composition of positive liposomes Most positive liposomes are composed of a neutral phospholipid and one or more positive components.
Neutral phospholipid components: The neutral phospholipid components used in positive liposomes are similar to conventional liposomes, such as cholesterol (cho1), phosphatidylcholine (PC), phosphatidylphenol ethanolamine (PE) )wait.
Positive ingredients: Most of them are synthetic double-chain quaternary ammonium salt surfactants, which have the advantages of good stability in vitro and biodegradability in the body, but they all have a certain degree of cytotoxicity.
⒊1.2 The mechanism of gene transfection mediated by positive liposomes. During the transfection process, the main function of positive liposomes is to form a complex with DNA, mediate the interaction with cells, and Release DNA into cells to achieve gene transfection.
⒊1.3 Application of positive liposomes in gene therapy As an alternative gene delivery carrier, positive liposomes have the following advantages:
⑴ It can prevent nucleic acids from being Substances in the body are degraded and can be specifically delivered to target cells;
⑵ Non-toxic, non-immune, biologically inert and biodegradable;
⑶ Easy to prepare and use Convenient, large DAN fragments can be transported into cells;
⑷The gene transfection rate is high, and 100% of isolated cells can express foreign genes instantly.
The other component of cationic liposomes is uncharged medium-sized lipid molecules called helper lipids. DOPE is an important helper lipid.
Stealth liposomes (long-circulating liposomes)
Stealth liposomes or long-circulating liposomes contain a hydrophilic polymer - polyethylene glycol. (PEG) Distearic acid phosphatamide (DSPE) derivative (PEG-DSPE). ⒊3.1 First-generation immunoliposomes (IML) refer to liposomes with monoclonal antibodies attached. Through the specific binding of monoclonal antibodies to target cells, the liposome-encapsulated drugs are directed to the target tissue, giving the liposomes active targeting.
⒊3.2 Second-generation immunoliposomes This technology includes long-circulating liposomes containing PEG, allowing antibodies or ligands to bind to the surface of the liposomes.
⒊3.3 In order to increase the targeting of long-acting liposomes, third-generation immunoliposomes connect antibodies or other ligands to polymers (such as PEG) on the surface of long-acting liposomes. ) chain, thereby avoiding the interference of the PEG chain on target recognition, and a new type of liposome was obtained. Flexible liposomes can be formed by adding a small amount of appropriate surfactant to the liposome component. Flexible liposomes can promote the transdermal penetration of water-soluble macromolecule drugs.
The particle size of ordinary liposomes is smaller than that of flexible liposomes, but due to the absence of sodium cholate, they are more rigid and difficult to promote transdermal transport of drugs.
Liposomes are an important technical method for miniaturizing drug-loaded particles. Although they are not solid powders themselves, they can be made into various solid powder dosage forms through preparation.