Preparation And Study Of Galactose Compounds For Diagnosis And Therapy

Hepatic diseases,especially hepatocellular carcinoma is the majority threat in developing countries.There is so much unsatisfactory that diagnostic drugs or therapeutic drugs for hepatic diseases showed insufficient curative effect and great side effect.Therefore,improving effect of drug and specific recognization of target cells are the current research hotspots.Based on galactose residue can be recognized by ASGPR receptor of hepatocytes,we respectively introduced galactose to diagnosis agents and treatment agents,and studied their preparation and property.It could provide basis and guidance for application.A galactose MRI contrast agents Gal-E-Gd-DTPA was synthesized in this paper.Commercial MRI contrast agents Gd-DTPA was used as parent structure,two synthesis routes including hydroxy protected route and galactose imine reaction route were explored.Finally,we successfully synthesized Gal-E-Gd-DTPA by the latter route,which showed short preparation period,convenient operation and low cost of materials.The structure of Gal-E-Gd-DTPA was characterized by NMR,FT-IR and MS.The calculated R₁ of Gal-E-Gd-DTPA is 7.3 mM^-1s^-1,which is 1.92 times higher than commercial Gd-DTPA.In vitro magnetic resonance imaging showed higher intensity than Gd-DTPA.Gal-E-Gd-DTPA showed potential in liver diseases diagnosis and was worth to be further studied.Liposome Gal-L was prepared by using galactose head cationic lipid Gal-lipid.Gal-L was⁸0 nm SUVs and showed low toxicity and superpior biocompatibility.MTT tests showed the IC₅₀ of Gal-L is above 50?g/mL.Hemolytic tests showed there is no obvious hemolysis below 200?g/mL,and no erythrocyte aggregation was saw below 30?g/mL.DOX loaded liposome Gal-DL was prepared,which was 110 nm stable spherical assembly.There was no obvious size and PDI changes after 1 mouth placed at room temperature.Gal-DL showed pH sensitive,which can release more drug at lower pH.Gal-L showed much more internalization in HepG2 cells than hydroxy head liposome HO-L,while there was no obvious different in MCF-7 cells that proved Gal-L have good hepatocellular target.Gal-DL showed better anti-cancer properties than free DOX and better anti-HepG2 properties than HO-L.Thus,Gal-L probably become a potential liver targeted therapeutic drug carrier.