Bioactivity Of Biocompatible Polymer Combining Small Molecule Drug

Most of the current antitumor drugs applied in clinic are low molecular weight compounds.They showed some advantages,such as effective,easy operations.But most of them showed considerable side effects.For example,in a short period of time after delivery,the blood concentration of drug treatment is often higher than the concentration required,and sometimes even higher than the minimum concentration of poisoning,causing human cases of poisoning,allergies,and so on.Some low-molecular-weight drugs metabolize in the human body faster,shorter half-life, easy excretion.After a period time,the plasma concentration will soon reduce to the minimum effective concentration below which affect treatment results.Polymer supporting can decrease drug side effects of low-molecular-weight drugs.In order to reduce its toxicity or improve their activity,some small molecular compounds were supported in natural polymer carriers in this thesis.Firstly,the research progress of polymer anticancer drugs and oxygen free radicals and antioxidants were reviewed.Secondly,the anticancer drug 5-fluorouracil was modified.In order to reduce the toxicity of 5-fluorouracil,we synthesized derivatives of 5-fluorouracil by chitosan and polyethylene glycol,and other bioactivity or biocompatibility of the polymer main chain or branched chain.The antitumor activities of these complexes were studied by SRB assay.The results showed that the cytotoxic activity of PEG(600)-GA-5FU (IC₅₀=24.53±0.35μg/mL to liver cancer cell Bel-7402)and PEG(600)-B-GA-5FU (IC₅₀=45.02±0.78μg/mL)are lower than that of 5FU(IC₅₀=13.79±0.13μg/mL).It indicated that the polymer modified with 5-fluorouracil showed high inhibition to tumor cell growth activity.These complexes could reduce the toxicity of 5-fluorouracil by comparison IC₅₀values.Thirdly,the small molecules salicylaldehyde-amino acid Schiff base metal complexes were immobilized on biopolymer,albumin.The antioxidant activities of these complexes were studied.Glycin and glutamic acid salicylaldehyde Schiff base metal complexes were prepared,and characterized by infrared and ultraviolet spectra. Then we prepared the BSA amino acid Schiff base metal complexes,and characterized by ultraviolet spectra and Native-PAGE.Their hydroxyl radical scavenging abilities were studied.The results showed that·OH scavenging rate of BSA zinc amino acid Schiff base complexes reached 47.2%.