Preparation And Characterization Of Amphiphilic Pachyman Micells For Sustained-release Drug Delivery System

Pachyman is a traditional Chinese medicine which is biocompatible,resourceful and cheap in China and Japan.Due to the water-insolubility,pachyman is lack of antitumor activity,which hinder its application.In order to make full use of this natural product,in this thesis,amphiphilic pachyman derivatives were synthesized by introduction of both carbonic chain(C4,C8,C12 and C16)and carboxymethyl groups into the main chain of pachyman.Those derivatives were able to self-assemble as micelles in water.It is expect that those micelles could increase water solubility of insoluble drugs,decrease the toxicity and side effect of the drugs.Also,it could be used as the carriers for sustained release drug delivery system.First of all.crude pachyman were purified.Purified pachyman firstly reacted with bromideas alkylating agent with different carbonic chain length and alkylated pachyman derivatives were obtained.Then alkylated pachyman derivatives sequentially reacted with monochloroacetic acid for carboxymethylation to get amphiphilic pachyman derivatives Infrared spectroscopy(IR)were conducted to confirm the structure of the pachyman derivatives and the degree of substitution of alkylation and carboxymethylation were determined.Secondly,doxorubicin,a potent anticancer drug,was chosen as model drugs in this study,was physically encapsulated into the pachyman micelles.TThe Particle size and size distribution,zeta potential,morphology(TEM),drug loading levels,encapsulation efficiency were all carried out to characterize the micelles.At last,in vitro drug release profile were measured and the results showed that amphiphilic pachyman micelles have a strong ability to release insoluble DOX in a sustained-release manner.The cytotoxicity of the micelles were performed against MG and L02 cells.The results showed that the cytotoxicity of four kinds of DOX-loaded micelles were concentration-dependent.Among them,the C16 drug-loading micelles showed the highest cytotoxicity towards U87MG cells.Moreover,the micelles were found to be well tolerate of L02 normal hepatic cells which indicated the biocompatibility of the synthesized pachyman micelles.