The Synthesis Of Selenium Derivatives Of Non-steroidal Anti-inflammatory Drugs And Their Application In Chitosan Drug Delivery

Non-steroidal anti-inflammatory drugs are a class of anti-inflammatory drugs that do not contain steroid structures.They have anti-inflammatory,anti-rheumatic,analgesic and antipyretic effects.They are widely used in the clinical treatment of osteoarthritis,rheumatoid arthritis,fever and pain relief.NSAIDs are currently one of the most commonly used drugs in the world.In recent years,the relationship between NSAIDs and tumors has attracted considerable attention.Epidemiological studies,laboratory indicators,and clinical studies have strongly demonstrated that NSAIDs can interfere with tumor progression and have a good protective effect on the body.Many epidemiological studies have shown that NSAIDs have a certain chemopreventive effect on epithelial tumors in general population.The representative studies shows aspirin(ASA)and other NSAIDs are used to reduce the incidence of tumors,especially intestinal tumors.Selenium(Se)is also one of the essential trace elements,which can also inhibit the growth of cancer cells.And it is related to multiple metabolic pathways in human body,its close relationship with human health has been generally recognized by the scientific community.Based on rational drug molecular design principles,a series of NSAIDs–Se derivatives include selenocyanates and diselenides were synthesized and characterized,their anticancer activities against the human cancer cell lines SW480,He La,A549,and Hep G2 were determined.Interestingly,most of the new compounds showed active in reducing the viability of different cancer lines.But there are also some shortcomings,such as insoluble in water,toxicity and so on.Chitosan is an excellent drug carrier which can solve these problems and easy to modify.As a new drug delivery system,chitosan carriers have attracted more and more attention due to their wide application in many drug delivery routes,such as loading of protein drugs,gene drugs,anticancer chemicals and so on.A series of modified chitosan(O-carboxymethyl chitosan)nanoparticles containing selenocyanates were synthesized and characterized.It was found that the prepared nanoparticles completely met the conditions of accumulation in tumor cells.Their grain size ranged from 100 nm to 200 nm.Their drug loading determined by ultraviolet spectrophotometry were about 50% and the encapsulation rates were about 20%,which lays a foundation for further research.