Preparation And Characterization Of Chitosan Derivates As Anti-tumor Drug Delivery System

Sustained/Controlled release drug delivery system (SCDDS), one of the fast-developing technologies over the past two decades in international medical community, by changing the dosage form or drug delivery methods, can overcome the shortcomings of traditional anti-cancer drugs. Although research on China's anti-cancer drugs and development of controlled-release drug delivery system have improved a lot, there is still a big gap when compared with developed countries abroad, therefore, it is of great significance to acquire independent intellectual property rights of sustained/controlled release drug delivery system for anti-cancer drugs. Chitosan and its derivatives are very promising candidates as ustained/controlled release carrier-materials for a variety of drugs, due to low toxicity and biological activity, which can have a dual effect when combined with drug treatment. It is reported that chitosan and its derivatives can be used as antitumor targeting-drugs-carrier. That drugs coupled with chitosan and its derivatives or chitosan and its derivatives as raw materials are mainly methods for the preparation of anti-tumor drug particulate formulations.The main work includes: (1) Establishment of tumor-targeted drug carriers by modified chitosan, and use X-ray diffraction, scanning electron microscopy, transmission electron microscopy, infrared spectroscopy and so on to analyze modified nanoparticles, research and analysis the influence of preparation methods and experimental conditions on the physical and chemical properties of chitosan; (2) Hydroxycamptothecin as a model drug to study modified carriers, such as water solubility, particle size, preparation methods, drug release characteristics of drug delivery systems, etc.; (3) MTT experiment to study carriers and drug loaded particles on the destruction of liver cancer cells; (4) Construction of S180 sarcoma model in mice to study the inhibitory to sarcoma solid tumor of drug-loaded system; (5) Construction of H22 liver cancer model in mice, using in-vivo-imaging system to study the targeting behavior of the drug system in vivo. The main findings are as follows; (1) Successful synthesis of water-soluble N-succinyl-chitosan and a new type of water-insoluble N-succinyl-chitosan under microwave irradiation; (2) Use of dialysis and membrane emulsification method to prepare a variety of HCPT-loaded N-succinyl-chitosan nanospheres, which can achieve different levels of sustained-release effect; (3) Water-soluble N-succinyl -chitosan can be accumulated in the lungs; (4) Water-insoluble N-succinyl-chitosan has a better inhibitory effect on S180 sarcoma solid tumor and destruction effect on H22 hepatoma cells, showed targeting behavior to liver tumor tissue in vivo experiments.