What Is The Basic Principle Of Nano-Targeting
After administration of a common pharmaceutical preparation, it is usually freely distributed in the body and then taken up by cells and organs. Due to the existence of various biological barriers in the body, such as the blood-brain barrier and the blood-retinal barrier, only a small part of the drug reaches the target site. The targeted preparation can selectively concentrate the drug on the lesion by means of the nanocarrier, and the lesion can be a target tissue, a target organ, or a target cell or a target in the cell.
According to the arrival location of the drug, the targeting can be divided into three levels: the first level refers to reaching a specific target tissue or target organ, such as liver targeting, lung targeting, and brain targeting; the second level refers to reaching a specific cell, such as hepatitis and liver cancer, which occurs in parenchymal cells in liver tissue rather than non-parenchymal cells (endothelial cells, Kuffer cells, etc.); the third level refers to a certain organelle that reaches a specific tissue or a specific cell, that is, intracellular targeting, such as gene therapy, in which the antisense oligonucleotide is delivered to the cytosol or the plasmid is delivered to the nucleus. According to the targeting principle of the targeted preparation, it can be further divided into a passive targeting mechanism, an active targeting mechanism and a physical chemical targeting mechanism.
Passive targeting
Passive targeting refers to the targeting of a drug or drug delivery system due to physiological endocytosis. Endocytosis is the internalization of the plasma membrane and can be divided into phagocytosis and swallowing. The former mainly captures particulate matter, while the latter mainly captures liquid. Cell phagocytosis is mediated by serum opsonin and related receptors on macrophages. After intravenous injection of passively targeted microparticles, the distribution in the body depends first on the size of the particles. Usually, when the particle size is 2.5~10pm, most of them are concentrated in macrophages. When they are less than 7μm, they are generally taken up by macrophages in the liver and spleen. The nanoparticles of 200~400nm are concentrated in the liver and cleared by the liver quickly. When less than 10nm, they accumulate in the bone marrow, particles larger than 7 μm are usually intercepted by mechanical filtration through the smallest capillary bed of the lung, and then taken up into the lung tissue or lung air bubbles by the monocytes. Swallowing is more common than phagocytosis and is found in almost all cells. The effect of swallowing is divided into liquid swallowing and absorption swallowing. Liquid phase swallowing is a non-specific, continuous process that is very useful for entering macromolecular substances into epithelial cells, certain endothelial cells, and various blood cells. Adsorption swallowing is a process of internalization by adsorption to the surface of the cell membrane.
Active targeting
Active targeting is the structural modification of a drug carrier to specifically recognize the target cell, thereby delivering the drug to the target zone in a targeted manner. According to different identification methods, active targeting mainly has two mechanisms of receptor-mediated and antibody-mediated targeting. The former mainly connects a suitable ligand on the nanocarrier, and the nanocarrier supports specific binding to the receptor expressed by the target site through ligand and receptor interaction. The latter is primarily the modification of the nanocarrier by an antibody that specifically binds to a specific or overexpressed antigen on the target cell.
In addition to the above-mentioned targeting methods, there are also targeting methods induced by external physical and chemical factors. For example, the drug-loaded magnetic nanocarrier can be enriched in the target tissue in the magnetic field region under the guidance of an external magnetic field and releases the drug. When the local target site is hyperthermia, the heat sensitive preparation can be urged to release the drug in the target area. The cell’s intrinsic transmembrane pH gradient under normal or pathological conditions will result the change of physical properties of a pH-sensitive carrier, and release drug. Ultrasound-sensitive drug carriers are capable of releasing drugs in specific tissues or organs under ultrasound excitation. These methods can control the release of the drug, which are beneficial to improve the drug effect and reduce the side effects of the drug.