氟尿嘧啶脂质体在小鼠体内的组织分布及靶向性评价研究

目的:研究氟尿嘧啶脂质体(FU-Lip)在小鼠体内的组织分布,并评价其靶向性。方法:将90只小鼠随机均分为10组,前5组静脉注射FU-Lip,后5组静脉注射FU注射液,剂量均为25mg·kg-(1以FU计),采用高效液相色谱法测定各组小鼠血浆、心脏、肝、脾、肺、肾中24h内的FU浓度,分析药物组织分布情况,以24h内的相对摄取率(re=AUC脂质体/AUC注射液)和靶向效率(te=AUC组织/AUC血浆)判断FU-Lip对主要器官的靶向性。结果:各组织中FU浓度均先升高后降低;与FU注射液比较,静脉注射FU-Lip后24h内的平均FU浓度在肝、脾中均升高,在其他组织中的浓度均降低;FU-Lip在肝中的re为17.13,其他组织的re均≤7.017;肝、脾中FU-Lip的te1与FU注射液te2的比值分别为5.616、2.301,其他组织均≤1。结论:FU-Lip能提高药物在肝、脾中的分布,具有肝、脾靶向性,尤其是肝靶向性。

Distribution of Fluorouracil Liposomes in Mice in Vivo and Evaluation of Its Targeting Performance

OBJECTIVE： To study the distribution of fluorouracil liposomes （FU-Lip） in mice in vivo and to evaluate its targeting performance. METHODS： 90 mice were randomly divided into 10 groups. The former 5 groups were treated with intravenous injection of FU-Lip, the latter 5 groups were treated with FU injection （25 mg.kg^-1 of FU）. The concentrations of FU in mice plasma, heart, liver, spleen, lung and kidney were determined by HPLC respectively. The distribution of fluorouracil in tissue was analyzed. The target ability of fluorouracil to main organs was evaluated by the relative tissue exposure （re=AUCliposome/AUCinjection）and targeting efficiency（te=AUCtissue/AUCplasma）. RESULTS： The concentrations of FU in tissues increased firstly then decreased. Compared with FU injection, the average concentration of FU in liver and spleen increased 24 h after intravenous injection of FU-Lip, while that of other tissues decreased. The r0 of FU-Lip in liver reached 17.13 while that of other tissues was lower than 7.017. The value of te1/te2 in liver and spleen were 5.616 and 2.301. That of other tissues was lower than 1. CONCLUSION： FU-Lip can increase the distribution of FU in liver and spleen with liver and spleen targeting property, especially liver targeting property.