紫杉醇胶束与紫杉醇注射剂在荷瘤裸鼠体内的组织分布  

Tissue distribution of paclitaxel micelle and paclitaxel injection in tumor-bearing mice

作　　者：韩滨[1] 刘骁[2] 孙菁[2] 周国亮[1] 张丽丽[1] 由振强[1] 余健[1] 宣尧仙[1] 

机构地区：[1]浙江省医学科学院安全性评价研究中心,浙江杭州310013 [2]复旦大学药学院,上海201203

出　　处：《中国新药与临床杂志》2011年第8期603-608,共6页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的评价紫杉醇胶束与注射剂在荷瘤裸鼠体内组织分布特征,为胶束制剂的临床应用提供参考依据。方法将Balb/c雄性荷瘤小鼠前肢腋皮下接种人结肠癌HT29细胞,待瘤体长到100 mm3左右后,分别经尾静脉注射给予紫杉醇胶束(PTX-PM)和紫杉醇注射剂(PTXI)均20 mg.kg-1,每3 d一次,共给药7次。于最后一次给药后30、60、180、360 min时处死裸鼠取血和各主要组织器官(心、肝、肠、肾、胃、肺、脾等),用HPLC法测定组织中紫杉醇的药物浓度。结果 2种制剂经静脉注射后,在各个时间点对各组织的药物分布趋势相似,以浓度高低依次为肝、肠、肾、胃、脾、肺、心等;PTX-PM组的紫杉醇在主要器官组织的浓度明显低于PTXI组(P<0.01或P<0.05)。其中PTX-PM组的紫杉醇在血浆中的浓度显著低于PIXI组(P<0.01),而30 min时PTX-PM组的紫杉醇在肝脏的浓度却高于PTXI组(P<0.01)。在各个时间点PTX-PM组的紫杉醇在主要器官组织的浓度与血浆浓度的比值明显高于PTXI组(P<0.01)。结论紫杉醇胶束有助于减少紫杉醇对血液系统的毒性,避免紫杉醇注射剂中聚氧乙烯蓖麻油引起的过敏反应,具有良好的临床应用前景。AIM To study tissue distribution of paclitaxel micelle （PTX-PM） and paclitaxel injection （PTXI） in order to provide a reference for clinical application. METHODS Male Balb/c nude mice were subcutaneously inoculated with HT29 colorectal cancer cell. When the tumor volume I〉 100 mm3, FFX-PM 20 mg·kg-1 and PTXI 20 mg·kg-1 were administered through tail vein every 3 days by 7 times. Blood and tissue samples were obtained at 30, 60, 180 and 360 minutes after the last administration to determine the concentration of paclitaxel （FIX） by HPLC. RESULTS The tissue distribution of PTX-PM and PTXI was similar, namely, they were distributed to the tissues of liver, intestine, kidney, stomach, lung, and spleen, etc. At all time points, FIX concentrations in the major organ tissue in PTX-PM group were significantly lower than those in PTXI group （P 〈 0.01 or P 〈 0.05）. Plasma concentration of PTX in PTX-PM group was obviously lower than that in PTXI group （P 〈 0.01）, while 30 minutes after the administration, FIX concentration in liver in PTX-PM group was higher than that in PTXI group （P 〈 0.01 ）. At all time points, the ratios of paclitaxel concentrations in major organ tissue to plasma concentrations in FTX-PM group were significantly higher than those in FIXI group （P 〈 0.01 ）. CONCLUSION PTX-PM could reduce the toxicity of FIX in blood system and avoid allergic reaction induced by poiyoxyethylene castor oil of paclitaxel injection.

关 键 词：紫杉醇 胶束剂 注射剂 组织分布 

分 类 号：R927.2[医药卫生—药学] R979.1