The Distribution Of Doxorubicin Hydrochloride Liposome In Important Tissues And Inflammatory Joints Of CIA Rats

Objective:To compare the distribution of doxorubicin and doxorubicin liposome in CIA rats important organs and inflammatory jointsMethods:70 Wistar rats were twice injected bovine collagen typeⅡto make a RA animal model.The RA Wistar rats were randomly divided into two groups, each group of 30 rats(magnetic male half), two groups of rats tailed vein injection doxorubicin and doxorubicin liposome respectively, each group were randomly divided into 5 groups(each group 6 rats,magnetic male half), each group in 6h, 12 h, 24 h, 48 h and 72 h to put the rats to death, to return the liver, lymph nodes, testes, ovaries, and inflammatory joints of the rats, then tested doxorubicin and doxorubicin liposome drug concentration in above organizations after processing on high performance liquid chromatographResults:(1)The RA model rats were poor mental and activities, weight loss. After the second collagen injection the arthritis index was 11.19±2.37, and joint swelling degree was6.54±1.42, compared with the nomal rats the arthritis index and swelling degree were increased significantly(P < 0.05). X-ray and pathological biopsy showed inflammation of the joints which was similar inflammatory change of RA. The success rate of RA model rats was 97.1%.(2) High performance liquid chromatography(HPLC) results showed that in 6h two groups of drug distribution in liver had no significant difference(P > 0.05), the rest of the time point drug concentration distribution of doxorubicin liposome group were significantly higher than doxorubicin group(P < 0.001); Inflammation of the joints concentration of doxorubicin liposome drug distribution at each time point were higher than in doxorubicin group(P < 0.05), and 24 h, 48 h, 72 h were significant difference(P <0.001); In 6h, 48 h the ovarian drug distribution had no significant difference(P > 0.05), in12 h, 24 h and 72 h drug concentration distribution of doxorubicin liposome group were higher than doxorubicin group(P < 0.05); In 6h, 24 h, 48 h two groups of drug distribution in testicle was no significant difference(P > 0.05), and 12 h and 72 h liposomes in testicle tissue distribution were higher than in doxorubicin group(P < 0.05); In 6h, 12 h, 24 h, 48 h doxorubicin liposome drug distribution in lymphoid less than doxorubicin group(P < 0.05),in 72 h the drug distribution has no difference(P > 0.05). Analysis and comparison between different organizations group showed liposome group of drugs with time increasing trends,and doxorubicin group presents downtrend with the passage of time.Conclusion:1. Doxorubicin liposome in inflammatory joints where strong together, liposome drug dosage can make drug targeted gathered in inflammation site;2. Doxorubicin liposome due to its long half-life and easy to be devoured by meshy endodermis system, drugs in the liver, ovaries, testicle organs distribution more, but in the ovarians and testicle organs drugs distribution showed no obvious difference compared to a single drug use.3. Liposome formulations can significantly extend half-life and residence time of drugs in the liver, inflammation of the joints, lymphoid tissue and reproductive system, with long cycle effect in the body.