The Preparation Of Macromolecular Drug Delivery System Based On Artemisinin Derivatives And Its Primary Bioactivity Research

Artemisinin and its derivatives is a kind of the most promising natural plant source active compounds,which is the first to be internationally recognized antimalarial drugs in our country.Although,artemisinin and its derivatives were reported to have anti-cancer activity,however because of its low bioavailability and high in vivo clearance rate,the drug in clinical application was limited.Nevertheless,based on the idea of drug delivery systems,the molecules of artemisinin derivatives were conjugated with the water soluble macromolecular polysaccharide make it obtained a certain solubility in water.At the same time,reduced its clearance rate in the organism,and improve the bioavailability.Xyloglucan is a kind of natural polysaccharide with some special biological activity,because of its well hydrophilicity and biocompatibility,it has certain application in drug delivery system.Pullulan polysaccharides is a kind of water-soluble excellent neutral polysaccharide,because it's are biodegradable,nontoxic,is often used in food additives.Hydrazone bond was widely used in pH-stimuli-responsive drug delivery system due to the property of it can rapid hydrolysis under mild acid medium.In this thesis,two kinds of aminated natural polysaccharides were synthesized under a certain experimental condition.The amount of amino group in the modified polysaccharides,was detected through the UV-spectrophotometry.The content of amino group in the aminated xyloglucan was 14.61%,and the aminated pullulan polysaccharide was 18.45%.At the same time,dihydroartemisinin(DHA)was simply modified with acetylpropionic acid and formylbenzoic acid,to introduce the carbonyl group and formyl group into the dihydroartemisinin structure and then two kinds of dihydroartemisinin derivatives were conjugated with aminated polysaccharide through the hydrazone bond.Finally,series of artemisinin-polysaccharide macromolecular drugs were prepared.We have selected the two kinds of water-soluble with higher degree of substitution macromolecular drugs XG-DAS 3.78 and Pul-DAS 11.52 to explore the inhibition effect against the HepG2 cells.Indicating that,after being conjugated with macromolecular polysaccharide,the inhibition effect against the HepG2 cell of dihydroartemisinin was improved.We believed that hydrophobic artemisinin derivatives were conjugated with hydrophilic polysaccharide and encapsuled by polysaccharide.Through the endocytosis enter the cell and release the drug under the intracellular biochemical microenvironment.Changed the way of small molecular enter the cell by free-distribution and thereby improvd the cell viability.The last but not the least,xyloglucan was a galactose rich polysaccharide turns out to be selective uptaken by ASGPR,which was specificity recognized the galactose residues and over expressed on the surface of HepG2.Vai receptor-mediated endocytosis,the sample of XG-DAS was entered the cell faster and displayed the better inhibition against the HepG2 cell.