羟喜树碱冻干粉针和纳米制剂在原位肝肿瘤小鼠的组织分布研究.pdfVIP

羟喜树碱冻干粉针和纳米制剂在原位肝肿瘤小鼠的组织分 布研究 文柳静（天津医科大学附属肿瘤医院，天津市肿瘤防治重点实验室，天津 300060 ） 摘 要： 目的测定静脉注射羟喜树碱（HCPT ）冻干粉针及纳米制剂后小鼠肝 组织、肝肿瘤及血液中的药物浓度，探讨改良纳米羟喜树碱对肝癌疗效的提升 作用。方法 以高效液相色谱法（HPLC ）检测小鼠血浆、正常肝组织和肝肿瘤 组织中羟喜树碱的浓度。原位肝肿瘤模型小鼠50 只，其中20 只随机分成两组， 每组 10 只，分别尾静脉注射HCPT 冻干粉针、纳米制剂，给药剂量 5mg·kg-1 给药后15min，内眦取血，测定肝组织、肝肿瘤及血浆中的药物浓度；另30 只 设生理氯化钠对照组、HCPT 粉针剂组和纳米HCPT 治疗组，每组10 只，给药 剂量5mg·kg-1 每周给药两次分别第一、四天给药，共给药2 周。两周后内眦取 血，测定肝组织、肝肿瘤及血浆中的药物浓度。结果 给药后15minHCPT 纳米 制剂血药浓度最高612.32±21.12µg·L-1 ，纳米HCPT 在肝脏及肿瘤组织中药物浓 度是HCPT 粉针剂组 12 和11 倍；给药两周后纳米HCPT 在肝脏、肿瘤组织中 药物浓度为89.45±16.35 µg·L-1 、93.74±18.91 µg·L-1 ，且纳米HCPT 在肝脏及肝 脏肿瘤组织中药物浓度与血药浓度（2.13±0.51 µg·L-1 ）比较差异有统计学意义 （P0.05 ）。结论 纳米HCPT 与粉针剂相比可稳定内酯环结构，增加组织亲和 力，提高靶向疗效，是可靠的改良新剂型。 关键词：羟喜树碱；纳米；肝癌；血药浓度 The Study of Organization distribution on Hydroxycamptothec and Hydroxycamptothec Nanoparticles Injection on Mice Hepatocarcinoma in vivo ABSTRACT: Objective To investigate the role to the liver cancer of the nano-modified hydroxycamptothecin(HCPT) ，the drug concentrations of the liver, liver tumors and blood of mices were determined ，which were injected from vein of injection-type HCPT and nano-HCPT. Methods According to the method of High-performance liquid chromatography （HPLC ）, the HCPT drug content in plasma ，liver tissue and liver tumor of mice was tested. Orthotopic liver tumor model in mice 50, 20 of which were randomly divided into two groups, 10 in each group were injected with HCPT lyophilized powder, nano-formulations, 5mg • kg-1 of dosage after administration of 15min, blood from inner canthal, the drug concentrations of the liver, liver tumors and blood were determined; divided into 3 groups of the other 33 of physiological sodium chloride based, HCPT injection and the nano-treated, 10 in each ，administered of dosage of 5mg • kg-1 in the first and fouth d