Preparation And Targeting Research Of A Metal Organic Framework Modified With Glycyrrhetinic Acid

Metal-organic framework materials are a class of novel materials that have the advantages of porosity,high specific surface area,formed by assembling inorganic metal ions and organic ligands.Compared with traditional carrier materials,MOFs have many characteristics such as pore size adjustability,large specific surface area,unsaturated metal coordination sites and structural surface easy modification.They have become a new type of carrier material with broad application.Glycyrrhetinic acid is an active glycyrrhizin aglycone of licorice.Clinical studies have shown that licorice has various pharmacological activities such as anti-inflammatory,anti-viral and anti-ulcer.Many GA-specific receptors are embedded in the liver cell membrane to specifically bind to GA,so GA has liver targeting.At present,the use of GA as a targeting group for drug delivery systems has become a research hotspot.In this paper,terephthalic acid was used as organic ligand and metal ion Zr to synthesize Ui O-66 material,and ciprofloxacin hydrochloride was loaded.It was characterized by IR,DSC,XRD and SEM.CIP@Ui O-66 was tested by antibacterial test.The results showed that Ui O-66 material was successfully synthesized in this project,and CIP was loaded into Ui O-66.The inhibitory effect of CIP@Ui O-66 was significantly stronger than that of CIP alone.In this paper,trimellitic acid and aminoterephthalic acid were used as organic ligands and metal ions Zr respectively to construct MOFs materials Ui O-66-COOH and Ui O-66-NH2 by one-pot method,respectively,which were connected with GA to obtain Ui O-66-COOH-1,4-butanediamine-GA and Ui O-66-NH2-GA.5-FU was loaded into the above two MOFs by impregnation to obtain 5-FU@Ui O-66-COOH-1,4-butanediamine-GA and 5-FU@Ui O-66-NH2-GA.Analysis and characterization were carried out by means of IR,DSC,XRD and SEM.The in vitro antitumor activity of 5-FU@Ui O-66-COOH-1,4-butanediamine-GA and 5-FU@Ui O-66-NH2-GA was tested by MTT assay.Liver targeting in mice of 5-FU@Ui O-66-COOH-1,4-butanediamine-GA and 5-FU@Ui O-66-NH2-GA by tissue distribution assay and in vivo imaging technique confirm.The results showed that Ui O-66-COOH,Ui O-66-NH2,Ui O-66-COOH-1,4-butanediamine-GA,Ui O-66-NH2-GA,5-FU@Ui O-66-COOH-1,4-butanediamine-GA and 5-FU@Ui O-66-NH2-GA were successfully prepared in this project.The prepared MOFs have a good crystal form,a regular octahedral structure,uniform particle size distribution,and diameter about 200 nm.The in vitro release results showed that 5-FU was released more efficiently in p H 5.5 PBS buffer than in p H 7.4 and p H 6.5,and released faster than 12 h before reaching more than 60%,and released substantially after 24 h.Completely,stable at around 80%.MTT results showed that 5-FU@Ui O-66-COOH-1,4-butanediamine-GA and 5-FU@Ui O-66-NH2-GA both showed high antitumor activity at the same dose.Both were stronger than 5-FU anti-tumor activity alone,and 5-FU@Ui O-66-COOH-1,4-butanediamine-GA was the most active.The results of tissue distribution test and in vivo imaging test showed that 5-FU@Ui O-66-COOH-1,4-butanediamine-GA and 5-FU@Ui O-66-NH2-GA have obvious liver targeting properties,and Ui O-66-COOH-1,4-butanediamine-GA linked to 1,4-butanediamine can better target liver tissue.The subject successfully prepared a drug carrier with liver targeting,and provided a good drug carrier for liver cancer drugs.