Research Of Character And Preparation Of PH-sensitive Doxorubicin Nanoliposomes Modified With Carboxymethyl Chitosan

Cancer is one of the leading diseases of death in the world. In cancer therapy, drug-therapeutics such as chemotherapeutants and gene drugs are widely used but their side effects limit their application, so new drug delivery systems have become the main method to solve this problem.In this paper, the doxorubicin nano-liposomes modified with carboxymethyl chitosan were prepared by film dispersion, ultrasonic dispersion and pH-gradient methods. The particle size and morphology of doxorubicin nano-liposomes modified with carboxymethyl chitosan were measured and the results showed that the particle size was small and narrow distribute and morphology was regular. The entrapment efficiency of carboxymethyl chitosan modified doxorubicin nano-lipsomes was related to materials,loading method and surfactants The release behaviours in different pH media was measured and the result suggested that doxorubicin nano-liposomes modified with carboxymethyl chitosan showed obviously pH response. After stored at different temperatures, the results showed that 4℃was the best stored temperature.The cytotoxicity,inhibition rate and drug uptake of doxorubicin,doxorubicin liposomes and doxorubicin nano-liposomes modified with carboxymethyl chitosan to different cells(MB231,Hela,Hepg-2 et al) were studied by MTT, flow cytometry and fluorescence microscopy method. The results showed that blank nano-liposomes modified with carboxymethyl chitosan can not inhibit the cell growth in a low concentration; the inhibition rate of different pharmacists was increased as time increased. Compared with regular doxorubicin liposomes, doxorubicin nano-liposomes modified with carboxymethyl chitosan can uptake more doxorubicin and owned better pesticide effect.The concentration in blood and tissue distribution of doxorubicin in different time of SD mice after iv doxorubicin,doxorubicin liposomes and doxorubicin nano-liposomes modified with carboxymethyl chitosan were measured by the methods of HPLC and fluorescence spectrophotometer. The pharmacokinetics of three samples showed that carboxymethyl chitosan modified doxorubicin nano-lipsome can enhance the circulation time in blood and decrease the concentration of doxorubicin in heart and kidney. Mice bearing tumor model was establish successfully and the antitumor effect and tissue distribution of doxorubicin,doxorubicin liposomes and doxorubicin nano-liposomes modified with carboxymethyl chitosan were tested and the result showed doxorubicin nano-liposomes modified with carboxymethyl chitosan owned the better antitumor effect, the tumor weight inhibition rate was up to 84.72% and the concentration in tumor was higher.