Biogastrone acid-polyethyleneglycol /chitosan liver target composite drug administration system and preparation thereof

Abstract

The invention relates to a novel liver target drug carrier-glycyrrhetinic acid-polyethylene glycol/chitosan or chitosan derivative liver target compound drug delivery system. During the preparation of the nano-drug delivery system, the liver target small-molecule glycyrrhetinic acid is firstly used for modifying amino polyethylene glycol by the different sites, then a water soluble big-molecule liver target compound is prepared and is mixed with a solution containing chitosan or chitosan derivative by a certain proportion, an ion cross-linking agent is added under the stirring condition, and a target group is introduced at the same time of the spontaneous formation of nanoparticles by physical winding and electrostatic interaction. The method of introducing the target group of the invention is novel, the formation of spheres is simple, the conditions are moderate, and the content of the target group is high (the weight percentage of glycyrrhetinic acid is 5 to 30 percent). The drug delivery system has strong killing capacity to the cancer cells, the in vitro experiments show that the drug delivery system has very strong binding capacity with the liver cells, and the high content of the target group can improve the liver target capacity of the drug delivery system, realize the target positioning of the liver and open a new way for the treatment of liver cancer.

Description

technical field [0001] The invention relates to the fields of biology and medicine, in particular to a glycyrrhetinic acid-polyethylene glycol modified chitosan or chitosan derivative liver-targeting compound drug delivery system and a preparation method. Background technique [0002] my country is an area with a high incidence of liver cancer, the incidence of primary liver cancer accounts for 45% of the world, the mortality rate ranks second in malignant tumors, and the 5-year survival rate is only 5%. Cancer can be treated with the help of organ transplantation, radiation therapy, chemotherapy and other methods. For liver cancer, the transplantation method is limited by the liver donor and has the problem of immune rejection; radiotherapy will directly damage the bile duct, so it is generally not used for the treatment of liver cancer. Therefore, "chemotherapy" using antineoplastic drugs plays an important role in the treatment of liver cancer. The current "chemotherapy...

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Problems solved by technology

[0005] Chinese patent CN101006983A discloses a preparation method of glycyrrhizic acid-modified chitosan/carboxylated chitosan composite drug-loaded nanoparticles. The fluorescence intensity of the modified nanoparticles in hepatic parenchymal cells is stronger than that of the control group. The patent is to use glycyrrhizinate as a targeting group and prepare drug-loaded nanoparticles through electrostatic interaction without involving glycyrrhetinic acid. It is reported that glycyrrhetinic acid has more binding sites than glycyrrhizic acid on the liver cell membrane); Chinese patent CN1743008A prepared chitosan nanoparticles modified by glycyrrhetinic acid and showed obvious liver targeting, but glycyrrhetinic acid directly modified chitosan nanoparticles The preparation conditions of sugar are relatively complicated, and the degree of sub

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