Preparation And Characterization Of Folate-conjugated Galactosylated Chitosan Drug Delivery Materials

Recently cirrhosis and cancer of liver serious threat people's hearth.In traditional drug delivery mode,drugs were difficult to be transported to targeting site specifically and accurately,which caused a low bioavailability, toxicity and side effect on other normal organ. Now,chitosan as a new non-viral vectors, was paid attention to by more and more countries and research department. But the charactor of targeting of drug carrier made of chitosan only was weak and insufficient in application. Galactose--- asialoglyco protein receptor ASGPR, and folic acid---folate receptor as new targeting systems are accepted by more and more people in recently. Based on the fact that ASGRP only expreassed on the surface of liver cell and the fact that folate receptor can be overexpresed on the surface of tumor cells but scarecely expressed on normal cells, the targeting can be achieved. So using Lactobionic acid and folic acid to modify chitosan can improve the target activity.1. Lactobionic acid and folic acid was be chosed to react with amino of chitosan to modify chitosan in two different kinds of methods. Through experiment what we got was as follows:1 From FA-GC FT-IR,we know that lactobionic acid and folic acid was successful grafted to chitosan. And it was match with the result of 1HNMR. In addition through 1HNMR of FA-GC, the degree of substidution of LA was got. And the degree of substitution of FA was estimated by UV-V; Through compare reaction product of two kinds of preparation method, it was known that both the degree of substidution of FA and LA by two step mothod was higher than by one step method.2. Because what we synthetize was a new kind of material which can not be found in nature, and it will be used in human body. So, the MTT experiment need to be done to confirmed whether the new material can use in human body. Though compare the results of new material and chitosan MTT experiment, it was known that the cytotoxicity of FA-GC is less than chitosan in the chosen experiment condition. And chitosan as a kind of natural polymer was of good biocompatibility and can be used in human body. So it can be concluded that our new material can be used in human body.3. FA-GC nanoparticle was prepared by the cross-linking of TPP and FA-GC. And we discussed the effects of many factors on the properties of nanoparticle. And we characterize it with the methods of granulometer and SEM. The size of the nanoparticle from SEM pHotograpH and from granulometer was matched well. And the nanoparticle we made can be use as drug carrier.4. Fluorouracil was used as the drug model,and carring fluorouracil nano-particle drug carrier which is of good stability was prepared; And the entrapment rate and loading rate was measured. The result was satisfactory.