Targeting of Liposomes

An important characteristic of liposomes is their targeting ability. The targeting of liposomes can be divided into passive targeting and active targeting. The former refers to the drug delivery to certain tissues based on the tendency of natural aggregation after injection into the body or targeted delivery to these tissues; the latter is either to make the liposomes target specific tissues by assembling specific homing devices on the surface of liposomes, or to make the liposomes unstable under certain physical conditions by changing the phospholipid composition of the lipid bilayer, so as to release the drugs or genes in specific target organs.

Passive targeting

• Targeted drug delivery of the reticuloendothelial system

After intravenous injection of liposome, it is quickly taken up by the reticuloendothelial system (RES) and concentrated in the liver, spleen, lung, lymph nodes, and bone marrow, which is of great significance for guiding the treatment of some diseases related to RES.

• Targeted drug delivery to tumors

The application of liposomes carrying macrophage activating factors can be quickly taken up by macrophages, greatly enhancing its ability to activate macrophages and subsequently clear tumors. In addition, the intravenous injection of liposomes can enter substantial tumors, inflammatory tissues, and vascular damage of hypertension, because the permeability of normal blood vessels in the capillary walls of these areas is high. Therefore, anti-tumor drugs carried by liposomes are more likely to accumulate in the tumor site than free drugs and play a higher anti-tumor effect. In addition, because polyethylene glycol (PEG) can significantly prolong the half-life of proteins after binding with proteins, the incorporation of PEG into the liposome membrane can make the liposome escape RES uptake since the stereochemical barrier effect of the long chain of PEG, which can prolong the circulation time of liposome and play a higher anti-tumor effect.

Active targeting

Active targeting means that the liposome is double-loaded with antibodies, sugar residues, hormones, receptors, and other homing devices to act on specific target organs and release the inclusion to play a role.

• Antibody-mediated targeted delivery

Immunoliposome (or affinity liposomes) can be conjured by monoclonal antibodies and liposomes and targeted to specific cells and tissues by the antigen-antibody-specific binding reaction.

• Receptor-mediated targeted delivery

Receptor-mediated targeting liposomes can target ligand-labeled liposomes in organs, tissues, or cells containing ligand-specific receptors by the specific interaction between receptor and ligand. Meanwhile, binding between receptor and ligand can promote the entry of liposomes into cells through the endocytosis pathway.

• Targeted delivery of pH-sensitive liposomes

The typical phospholipids for the preparation of Ph-sensitive liposomes are dioleylphosphatidyl ethanolamine (DOPE) and phosphatidyl ethanolamine (PE). When the ambient pH value reaches a certain value, PH-sensitive liposome membranes fuse with adjacent membranes (acid-induced fusion), causing the liposome membranes to rupture and release the contents into the cytoplasm.

• Targeted delivery of temperature-sensitive liposomes

A temperature-sensitive lipid is a kind of lipid microsphere that can carry drugs and release drugs effectively under high-temperature conditions. Targeting drug delivery with temperature-sensitive liposomes combined with temperature warming of the lesion site is a new targeting strategy for liposomes. The principle is that the liposome constructed by some lipids has a specific phase transition temperature, and the liposome remains stable in an environment lower than its phase transition temperature. When the liposome reaches the liquid crystal phase transition temperature, the acyl chain disorder and activity of the phospholipid increase, the fluidity of the membrane increases, and the encapsulated drug release rate increases.

• Magnetic liposome

Ultrafine magnetic powder Fe₃O₄ or dextran magnetic beads can be inserted into the liposome, and the magnetic field generated by the external magnetic field (such as a permanent magnet placed outside the body) can be used to locate the target site in vivo.