纳米炭吸附丝裂霉素C腹腔化疗的实验研究

Experimental study of intraperitoneal chemotherapy with mitomycin C bound to carbon nanopaticles

目的:探讨纳米炭(carbon nan-oparticles,CNP)吸附丝裂霉素C(mito-mycin C,MMC)腹腔化疗的药代动力学特征。方法:建立人胃癌裸鼠模型,静脉注射MMC、腹腔注射水剂MMC及腹腔注射MMC-CNP,于给药后不同时间点解剖裸鼠提取标本,高效液相色谱(HPLC)法测定淋巴结、肠系膜、腹腔液及血浆的MMC浓度,分析不同方法的药代动力学特征。结果:MMC-CNP可以在淋巴结、肠系膜和腹腔液形成高药物质量分数,并持续维持至少24h,血药浓度极低,P<0.01。水剂MMC腹腔化疗可以形成短暂的腹腔液高药物质量分数,但是不能在淋巴结、肠系膜中形成高浓度,P<0.01。静脉MMC化疗可以在肠系膜内形成短暂的高药物质量分数,但是淋巴结和腹腔液药物质量分数低,血药浓度高,P<0.01。结论:MMC-CNP腹腔化疗具有淋巴靶向性及功能缓释性,是一种预防及治疗进展期胃癌腹腔转移的有效方法。

OBJECTIVE： To analyze the pharmacokinetics of intraperitoneal chemotherapy with MMC bound to carbon nanoparticles. METHODS： A nude mouse model with transplanted human gastric cancer was established. The mice were given MMC by iv or intraperitoneal （ip） injections, or given ip MMC bound to carbon nanopaticles （MMC-CNP）. Pharmacokinetic assays were carried out at different time points, to measure the MMC concentrations by HPLC and the results were compared. RESULTS： The MMC concentration in lymph nodes, mesentery and peritoneal exudate of MMC-CNP group was significantly higher than that of MMC solution ip group and MMC iv group, P〈 0.01. On the other hand, the MMC level in plasma was significantly lower than that in the two control groups, P〈0.01. High MMC level was maintained at least 24 hours in the MMC-CNP group. Intraperitoneal chemotherapy with MMC solution resulted in a low MMC concentration in the mesentery and lymph nodes, and only a transient high level of MMC in peritoneal exudate, P〈0.01. After iv administration, a significantly higher level of MMC concentration occurred in the plasma, but only a shortly increased concentration of MMC in the mesentery, and lower concentration in peritoneal exudate and lymph nodes as compared with those in the other two groups, P〈0. 01. CONCLUSION： Carbon nanoparticles is a perfect drug delivery system for lymphatic targeting in preventing metastasis and recurrence of advanced gastric cancer.