Injection Nano Drug Delivery System II
As mentioned above, liposomes, microemulsions and nanoemulsions are used for pharmaceutical transportation through the injection of nanometer drug delivery system. And this article will further introduce other nano-carriers that can be administered by injection nano-administration, including: nanoparticles, polymer micelles, nanogels, polymer complexes, and nanosuspensions.
Nanoparticles, as a carrier for the injection of nano-drug delivery systems, have their advantages mainly in: 1. The more hydrophilic the surface of the surface-modified nanoparticles, the smaller the uptake by macrophages. 2. The in vitro release of drugs can be adjusted by controlling the increase in PEG molecular weight and content or the decrease in copolymer molecular weight. 3. The distribution of nanoparticles in various organs and tissues in the body is related to the size of the nanoparticles and the way of administration. 4. Among the negatively charged single nanoparticles, the greater the zeta potential, the easier it is to be swallowed by hepatitis C macrophages after intravenous injection, while the positively charged nanoparticles are easily trapped by pulmonary capillaries and targeted to the lung. By using these properties of nanoparticles, high-quality polymer nanoparticles and solid lipid nanoparticles can be prepared for injecting drug carrier systems.
Polymer Micelles
After the concentration of amphiphilic polymer molecules increases to a certain value, the hydrophobic regions of the amphiphilic polymer molecules are attracted to each other due to intermolecular forces such as hydrophobic interaction, electrostatic interaction, hydrogen bonding, and so on, forming spherical micelles. The polymer micellar carrier has a wide range, stable structure, good tissue permeability, long retention time in the body, high target effectively, and has a small particle size, which is not easy to be absorbed by the reticuloendothelial system and eliminated by the liver and kidneys. The drug-loading mechanism of polymer micelles is that hydrophobic drugs are encapsulated in a hydrophobic core, which is equivalent to dissolving in non-polar solvents, and hydrophilic drugs are loaded in a hydrophilic shell. This is because the barrier shell contains a large amount of solvent water and the core-shell junction Can be loaded with amphiphilic drugs. Generally, drugs in the hydrophobic core can be released slowly, so polymer micelles are often used as carriers for hydrophobic drugs. The modification of the hydrophobic core of polymer micelles is conducive to carrying drugs with different properties; and the design and optimization of its hydrophilic shell can make the drug-loaded micelle system escape the phagocytosis of mononuclear macrophages, giving it “invisibility” . Studies have found that polymer micelles prepared with cell penetrating peptide (TAT) and pH-sensitive lipids can construct a kind of TAT that hides the cell penetrating peptide during circulation in the body, and penetrates tumor blood vessels into the tumor acidic microenvironment. After that, TAT is automatically ejected to mediate the carrier implementation of the nano-drug delivery system containing doxorubicin.
Nanogel
Nanogels are nanoscale hydrogels, a polymer network composed of amphiphilic or water-soluble polymers through physical or chemical action. It is easy to disperse in water, has a hydrophilic and soft appearance, contains a lot of water, can wrap a large number of bioactive molecules (small and large molecules), and has good compatibility in the body. In addition to physical packaging, drugs can also be wrapped in nanogels through salt formation, hydrogen bonding, and hydrophobic interactions. The surface of the nanogel is hydrophilic, it is not easy to be opsonized in the blood, and can avoid the phagocytosis of macrophages, so it is better distributed in the tumor. Nanogel has high encapsulation efficiency, good stability, and environmental sensitivity (such as ionic strength, pH, temperature), and is a good nano-carrier for injection administration.
Cationic polymers are a type of non-viral vector used for gene delivery in vivo, mainly for the delivery of nucleic acid drugs. The complex of nucleic acid and cationic polymer, that is, the multimeric complex, can be taken up by the cell through the endocytosis pathway, and its transfection efficiency depends on the rate of release of nucleic acid into the cytoplasm after the uptake by the cell. The use of polymers with buffering capacity or fusion peptides that can form pores on the membrane can increase the transfection efficiency mediated by the polymer complex.
Nanosuspension
Nanosuspensions can be delivered in a variety of ways, such as oral, injection, inhalation, transdermal, etc., among which injection administration has significant advantages. On the one hand, compared with nano-carrier preparations, nano-suspensions do not require carrier materials, are not restricted by the encapsulation rate and drug loading, and can meet the needs of high-dose and high-concentration preparations; on the other hand, compared with traditional injections, nano-suspensions does not have the toxicity of excipients. Traditional injections of poorly soluble drugs require a large amount of surfactants or co-solvents to improve the solubility of poorly soluble drugs, such as surfactants polysorbate 80, polyoxyethylene castor oil. These injections are prone to hemolysis and allergic side effects, organic The injection of solvent propylene glycol is easy to cause intense pain, and patients have poor compliance. Due to the toxicity of the excipients, the dosage is often limited, and the effective effect cannot be exerted. Nanosuspensions are generally aqueous dispersions, do not contain organic solvents, and only contain a small amount of stabilizers in the prescription, and this stabilizer is selected based on its safety in injections, so nanosuspensions has very low toxicity.
Nano drug delivery systems mostly use injection, especially intravenous injections. Because their particle size is nanometers, they are conditioned in the blood after intravenous injection, then recognized and swallowed by macrophages, and transported to Liver, spleen, lung and other tissues can achieve passive targeting. Since most normal tissues have non-leaking microvasculature, the drug-loaded nano-drug system can also accumulate in large amounts in the capillaries of the tumor tissue with permeability, so that the drug is concentrated in the tumor cells, that is to enhance the penetration and retention effect . When the nano drug delivery system is small enough and hydrophilic molecules are attached to the surface, it can escape macrophage phagocytosis and rely on active targeting molecules to target the target cells to achieve active targeting. It should be said that the nano drug delivery system has a wide range of applications through injection and can achieve tumor targeting, hepatocyte targeting, and macrophage targeting, and has a broad prospect in tumor, hepatitis, and gene therapy.