Study On The Application Of Thiolated Chitosan Coated Zr-NDC As A Carrier For Oral Delivery Of 5-fluorouracil

Cancer is a kind of disease that is difficult to cure for human beings.Chemotherapy is most important treatment method,and oral administration of chemotherapy drugs is a trend.Due to a series of advantages,MOFs have become promising multi-functional material.Among them,Zr-MOFs are particularly suitable for biological applications due to their optimal stability to hydrolysis and low toxicity,but MOF is not acid-tolerant,limiting its use as an oral delivery carrier.MOFs coated TCS can not only improve the stability of MOFs in the stomach,but also improve the permeability of intestinal mucosa.Therefore,this project is to synthesize TCS coated drug carrying MOF,and investigate its toxicity to several cells and its absorption in the intestinal tract of rats.MOF——Zr-NDC was synthesized from zirconium tetrachloride and 2,6-naphthalenedioic acid with regular octahedron.5-FU was taken as the model drug and loaded into MOF.The ratio of 5-FU to MOF,stirring time and ultrasonic temperature were taken as the objects,and the drug loading of MOF was taken as the evaluation index.Through the central point design,the optimal preparation process was obtained as follows:X₁=2.2、X₂=9.1、X₃=57,the drug loading capacity of MOF@5-FU prepared was 0.69 g·g^-1.The oral drug delivery system（TCS-MOF@5-FU）was constructed by using TCS and was characterized by a series of means.In vitro release results showed that without TCS coating,the structure of MOF collapsed in the stomach and a large amount of drug was released.After being coated with TCS,MOF successfully passed through the stomach and released the drug in the intestine.Cell experiments results demonstrated that the drug inhibited cancer cells more than normal cells.TCS-MOF@5-FU had a high inhibitory effect on cancer cells.The Ka and P_app of the drug in duodenum were larger,followed by jejunum and ileum,and colon was the smallest.In addition,the absorption of TCS-MOF@5-FU was higher than that in 5-FU and MOF@5-FU groups.The oral drug delivery system of TCS-MOF@5-FU was successfully constructed.The drug delivery system can protect the drugs from the stomach to the intestine smoothly and achieve more absorption in the duodenum.This is a new oral drug delivery system,which provides experimental basis for the oral drug delivery of anti-cancer drugs.