Colon-Targeted Nanoparticles
The colon is located between the cecum and rectum and is divided into four parts: the ascending colon, the transverse colon, the descending colon, and the sigmoid colon. Its main function is to absorb water and electrolytes and solidify the contents into feces. The colon cannot actively absorb substances such as sugar, amino acids, and small molecule peptides. Its absorption function is mainly achieved by the content of the colon staying for a long time. Some drugs can be absorbed by passive diffusion. The physiological environment of the colon has the following characteristics: ① The pH is generally 6.5 to 7.5, which varies depending on the diet structure and physiological conditions; ② Colonic motility is slow, so the drug stays in the colon for a long time. And the colon wall is less resistant to macromolecular penetration than the small intestine. ③ It is rich in more than 400 kinds of beneficial bacteria groups, and there are about 1 X 1011 bacteria per ml of intestinal fluid, forming a huge colony gradient with the small intestine. ④ Proteolytic enzymes and peptidases are not secreted by intestinal wall cells, but are mainly produced by bacteria in the intestine. Their concentrations and activities are much lower than those in other parts of the digestive tract. These physiological characteristics of the colon site provide multiple opportunities for nanotechnology to be applied to colon targeted drug delivery.
The colon-targeted nanometer drug delivery system can prevent the drug from being released in the stomach, duodenum, jejunum, and ileum, and it is not released until the drug is delivered to the ileocele, thereby exerting local or systemic treatment of the colon. Nanoparticles have a small particle size and strong adsorption ability, can penetrate the colonic epithelial tissues or capillaries in tumors, specifically gather in the colon, make the drug directly released at the lesion, increase the local drug concentration. The slow release of the drug in the colon is also conducive to exerting a long-lasting effect, and is beneficial to the treatment of rhythmic diseases such as asthma, angina pectoris and arthritis. Therefore, colon-targeted nanometer drug delivery is a promising new drug research field, and has important clinical application value.
Colon targeted nano drug delivery system
The nanoparticles currently used for colon-targeted administration mainly include: nano prodrugs, lectins-mediated colon-targeted nanoparticles, solid lipid nanoparticles, liposomes, nanoemulsions, and polymer micelles.
Nanoprodrug
Nano-prodrugs can be prepared by combining drugs with high-molecular materials that can be biodegraded by specific enzymes secreted by microorganisms of the colonic flora through various chemical bonds. After taking the medicine, because the stomach and small intestine lack the enzyme system that degrades the prodrug, it is guaranteed that the drug will only be released in the colon. Colon-targeted prodrugs include azo prodrugs, azo-adhesive prodrugs, and glycoside prodrugs. Because G-glucuronidase is mainly present in the lower part of the gastrointestinal tract, these prodrugs hydrolyze less in the stomach and the proximal part of the small intestine, while increasing hydrolysis in the distal part of the small intestine, the highest amount of hydrolysis in the cecum.
Lectin-mediated colon targeting
Lectins are a class of bivalent or multivalent proteins that specifically bind to glycosyl groups on the cell surface, and have specific ability to recognize lectin receptors in certain tumor cells. Lectins are not immunogenic and can be multivalently bonded to certain drugs, toxic proteins, and radioisotopes, while maintaining their activity unchanged. For example, peanut agglutinin (PNA) is a protein extracted and purified from peanuts and has the following characteristics: ① no agglutination effect on normal lymphocytes and blood cells; ② no obvious toxic and side effects; ③ acidic environment and a variety of enzyme systems PNA binding sites are well on the cell membrane of the cancerous colorectal / rectal epithelial cells and in the cytoplasm of the top of the cells, and PNA receptor significant differences between cancer tissues and normal tissues. Therefore, peanut lectin can be used as a nanoparticle targeting pathway.
Carbofluoride (HCFU) solid lipid nanoparticles (SLN) were prepared using lecithin and glyceryl tristearate as carrier materials by a thin-film ultrasound method. Studies have found that HCFU-SLN can effectively reverse the multidrug resistance of colorectal cancer cells and has significant targeting.
In colon targeting research, it was found that the preparation of doxorubicin nanomagnetic liposomes, under the action of an external magnetic field, can effectively aggregate the drugs into colon tissues, reduce the concentration of drugs in the heart and kidneys, significantly increase the concentration of drugs at the target site, and reduce toxic side effects.
Nanoemulsion
The paclitaxel was mixed with an ethanolic solution of glyceryl monostearate to form an organic phase; soy phospholipid, Planic F-68, and polysorbate 80 were dissolved in water to form an aqueous phase, and the two were mixed to form a paclitaxel nanoemulsion by ultrasonic emulsification. Nude mouse human colon cancer cell transplantation experiments confirmed that the nanoemulsion can overcome the resistance of tumor cells to paclitaxel, have anti-vascularization effect, have strong killing power for transplanted tumors, improve drug bioavailability, and show significant colon targets Action
Polymer Micelles
Curcumin is a safe and effective anticancer agent, but its hydrophobicity limits its clinical effect. Encapsulation of curcumin in PEG-PCL by one-step nano-precipitation method to form curcumin polymer micelles can significantly improve curcumin solubility and significantly inhibit C-26 colon cancer cells, and has significant colon tumor cell targeting effect.
In summary, nanotechnology enables nanocarriers to specifically bind to colon cells, thereby achieving safe and effective colon-targeted administration. Although preliminary studies have been made on the preparation, structure, and properties of nanomaterials, a lot of work remains to be done in areas such as application development. For example, colon-targeting nanocarriers have a small drug load, which may lead to colonic colonization after drug nanocrystallization Poor targeting, the mechanism of colonic targeting of nanomedicines is unclear, and the low bioavailability of drugs, etc. These difficulties need to be further resolved.