The Design And Preparation Of Polymeric Nano Micelle For Targeting Tumor Treatment

Cancer is a serious threat to the health of human body, it has become the first Chinese resident’s death causes. Each year 1.8 million people died because of tumor. It causes a serious social problem. So far, taking drugs for cancer is still one of the three major treatment methods. However the solubility of antitumor drug is low; it is hard to be absorbed by human body, and it also do not have cells selectivity. It will target on the normal cells and cancer cells at the same time. This unselective toxicity limits the widely use of antitumor drugs. Therefore, there is a need to improve the antitumor drugs biological utilization rate and reduce their toxicity. In this paper, we synthesized CHS-HPCHS-FA which has targeted effect and pH responsive effect on drug delivery, and we further investigated the drug delivery mechanism.This paper mainly includes the following aspects:(1) preparing polymer CHS-HPCHS and CHS-HPCHS-FA, using FTIR and element analysis to characterize the products. Changing the ratio of CHS to control the structure of the polymer. We obtained CHS-HPCHS and CHS-HPCHS-FA with the replacement rate of 2% and 6%. The replacement rate of FA is 0.9%.(2) Using ultrasonic dialysis method to synthesis 6%CHS-HPCHS, 2%CHS-HPCHS and 6%CHS-HPCHS-0.9%FA micelles. The critical micelle concentration, the size and morphology of drug loaded micelles and drug release properties of micelle are investigated. We also investigated the pH responsive mechanism at pH controlled drug release environment. Results show that the critical micelle concentration will be lower if we increase the hydrophobic segments which will form smaller micelle radius with high efficiency of drug delivery. The in vitro dissolution results showed that the drug loaded micelles in pH5.5 have a faster drug release rate than that of pH7.4, reflecting the response of controlled release effect.(3) We use the MCF-7 cell to study the cytotoxicity of the blank micelles and drug loaded micelles active targeting effects. Two kinds of blank micelles have IC-50 within 24h higher than 1000mg/ml, indicating the biocompatibility of blank micelles are good. The folic acid modified micelles’ 48h IC-50 value is 1.12mg/ml, the cytotoxicity is 1.31 times of those without folic acid modification, combined with laser scanning confocal observation,24h folic acid modified micelles have been completely get into the nucleus, folic acid modify free micelles are partially in the cytoplasm. All this shows that the modified CHS-HPCHS-FA micelles exhibit the active targeting effect and can be more quickly swallowed by tumor cells. It is a better antitumor drug carrier.