Preparation And Evaluation Of Several New Drug-loaded Materials Used In Sulforaphane

Sulforaphane is one of the best anti-cancer natural active substances. It has very good control effect on the esophagus, lung, colon, breast and liver cancer. Sulforaphane has a lot of restrictions in application of food and medicine because of its pH instability and thermal instability. Some new drug delivery systems could address these problems for sulforaphane better clinical application in cancer research.Microspheres, microcapsules, and liposomes as drug carriers can increase drug solubility, enhance drug absorption through the film, targeted delivery and be smaller size which could pass the cell membrane and more other advantages which make they research hotspot. In order to solve the sulforaphane instability at high temperatures and instability under alkaline conditions which make it could not targeted release in the colon, in ths paper, we prepared the pH-responsive carboxymethyl chitosan hydrogel, alginate-carboxymethyl-chitosan microcapsules, polylactic acid microspheres, liposomes, and sulforaphane microcapsules prepared by spray drying embedded of maltodextrin. And we investigate and compare the optimization of process conditions, surface morphology, degree of swelling, drug loading and in vitro release rate behavior of the systems.This dissertation is divided into five parts. The first part was preparing pH-responsive hydrogels by crosslinking, and studied the effect of different amount of glutaraldehyde on the degree of hydrogel swelling; in the second part we prepared sodium alginate-carboxymethyl chitosan microcapsules by interfacial polymerization. The surface morphology was studied at different pH, the results showed that the microcapsules were round and had smooth surface under acidic conditions while the surface folds and had similar pore structure under alkaline conditions. We found the inorganic salts had the burst effect in microcapsules too, the results showed the microcapsules can enhance the stability of sulforaphane.In the third part, polylactic acid microspheres containing was prepared by sonication, the concentration of oil phase and water phase and phase volume ratio of oil and water, ultrasonic time was investigated. And through the optimization of preparation conditions, uniform microspheres were obtained, the average particle size was1274nm, the polydispersity coefficient was 0.342.For a diameter less than 200nm nanoparticle could pass plasma membrane through endocytosis and pinocytosis which made the dug directly delivering to the nucleus of tumor cells, so in the fourth part,a diameter less than 200nm lipsome was prepared by ultrasonic dispersion. The drug loading rate reached to 29.32%. PartⅤwe prepared sulforaphane microcapsule by spray drying with maltodextrin and carboxymethyl chitosan as wall material respectively, sulforaphane stability of the microcapsules was studied in 50h, the results showed that in the same ratio of core material and the wall material, maltodextrin microcapsules stability were better than carboxymethyl chitosan microcapsules.Through the comparative studies of this paper, the results showed that sodium alginate-carboxymethyl chitosan microcapsule had the best pH response and targeting effect during the drug systems; liposomes had obvious advantages in the preparation uniform small size microspheres. Different hydrophobicties of different materials led to the different drug loaded behavior and in vitro release rate. Sodium alginate-carboxymethyl chitosan microcapsules are expected to be the proper system for sulforaphane treatment of colon cancer.