Passive targeting preparation (passive targeting preparation) is a natural targeting preparation. The drug-carrying particles are taken up by the macrophages of the monocyte-macrophage system (especially the kupffer cells of the liver), and are transported to organs such as the liver and spleen through normal physiological processes, but it is difficult to reach other target sites. The distribution of passively targeted particles in the body after intravenous injection depends first on the particle size of the particles. Usually, when the particle size is 2.5-10 μm, most of the particles accumulate in macrophages. Nanoparticles smaller than 7 μm are generally taken up by macrophages in the liver and spleen, while nanoparticles of 200-400 nm are concentrated in the liver and rapidly cleared, and nanoparticles smaller than 10 nm slowly accumulate in the bone marrow. Particles larger than 7 μm are usually retained by the smallest capillary beds of the lungs by mechanical filtration and are taken up by mononuclear leukocytes into lung tissue or alveoli. In addition to particle size, particle surface properties play an important role in distribution.
The uptake of particles by the monocyte-macrophage system is mainly accomplished by the adsorption of particles to blood conditioning agents (opsonin, including igg, complement c3b, or fiber-binding fibronectin) and to the relevant receptor on the macrophage: particles adsorbed to conditioning agents adhere to the surface of the macrophage, and then are taken up by the macrophage through intrinsic biochemical effects (endocytosis, fusion, etc.). Uptake by macrophages through intrinsic biochemical effects (endocytosis, fusion, etc.). The size of the particles and their surface properties determine which conditioner components are adsorbed and to what extent, and thus the pathway and mechanism of phagocytosis.
Drug-carrying particles of passively targeted formulations include: liposomes, emulsions, microcapsules and microspheres, nanocapsules and nanospheres.
①Liposomes
These are miniature vesicles formed by encapsulating a drug within a lipid-like bilayer, as lipid-like spheres or liquid crystal microcapsules.
②Targeted emulsions
The targeting of an emulsion lies in its affinity for lymph.
O/W or O/W/O intravenous complex emulsions made of oily or lipophilic drugs allow the original drug to concentrate in macrophage-rich tissues and organs such as the liver, spleen, and kidney.
③ Microcapsules and microspheres
refers to the tiny spherical entities or vesicles formed when the drug is dissolved or dispersed in excipients.
④ Nanocapsules and nanospheres
Nanocapsules are of the drug reservoir membrane shell type and nanospheres are of the matrix skeleton type. Particle size 10~1000nm in water to form a solution similar to a capsule. It can penetrate the cell wall to hit the target point without blocking blood vessels, and can be targeted to liver, spleen and bone marrow. Microcapsules are a new type of dosage form utilizing natural or synthetic polymer materials or **** polymer (capsule membrane material) to wrap the drug. The capsule membrane has the effect of isolating the outside world from the drug, preventing the oxidation, hydrolysis and volatilization of the drug, masking undesirable odors, and reducing the contraindications of compound preparations. China has developed more than 10 kinds of Chinese medicine volatile oil microcapsules, such as mustard oil microcapsules can improve the stability, mask the bad odor of allicin microcapsules, etc., but also the preparation of special properties of microcapsules (magnetic microcapsules, pH-sensitive microcapsules) to play a role in the targeted release of drugs.
Microspheres are tiny spherical entities formed by dissolving or dispersing drug molecules in excipients, and they are mostly made of biodegradable materials, such as proteins (gelatin, albumin, etc.), saccharides (agarose, starch, dextrose, chitosan, etc.), and synthetic polylipids (such as poly(lactic acid) and poly(propylenoic ester ethyl ester)****polymer, etc.), and they can be made of bioadhesive properties such as diethylmethylethylglucose, serum albumin, and degradable starch. Microspheres made with bioadhesive properties.
Targeted microspheres can be divided into three categories: ordinary injectable microspheres, embolic microspheres, magnetic microspheres. Such as polymer biodegradable polycarbonate [poly (DTC-co-TMC) 90:10] as a carrier, to prepare a new type of magnetic microspheres containing tumor necrosis factor (INF) and has a strong magnetic polycarbonate. The microsphere capsule formulation of goldfinch isoflavin (Genistein, 4′,5,7-trihydroxyisoflavone) made with chitosan as the carrier was highly selective to the lungs and spleen, and the drug maintained a certain blood concentration for a longer period of time, with a certain degree of slow release. Nanoparticles are solid colloidal particles of nm particle size made from natural macromolecular substances (e.g., albumin, gelatin, ethyl cellulose, etc.) or synthetic macromolecular substances (e.g., poly(alkyl cyanoacrylate) (PACA), acrylic acid*** polymer, etc.), which are classified into drug reservoir membrane-shell type nanocapsules and matrix-skeleton type nanoparticles. The advantages of these carrier formulations are biodegradability, low immunity, diverse formulation formation, high encapsulation rate and good stability. For example, 125I-albumin-astragalosan nanoparticles (168±62) nm were prepared by emulsification method, and the study showed that they were mainly distributed in the liver, spleen and lungs after oral administration to mice. The solid liposome nano of camptothecin prepared by hot melt dispersion technique, animal experiments showed good targeting of the preparation in vivo. Recent studies have shown that the solid-liquid two-phase drug delivery system, in which triglycerides and oils are conjugated, has a greater drug loading capacity than the traditional stearic acid drug delivery system and is more suitable for clinical use.