摘要
目的:对自制紫杉醇自组装前体脂质体(PSAP)在大鼠体内的组织分布进行研究,并与市售紫杉醇注射液(Taxol)的组织分布特征进行了比较。方法:SD大鼠以5 mg/kg的剂量尾静脉注射PSAP及Taxol,建立LC-MS/MS方法,于给药后不同时间测定组织中的紫杉醇药物浓度,对两种制剂的大鼠体内组织分布特征和靶向性进行评价。结果:PSAP与Tax-ol组相比,肝、脾、卵巢、子宫中的药物分布明显高于Taxol组(P<0.05),在以上各组织中的相对摄取率(re)大于1;肺、肾中的分布与Taxol组无明显差异(P>0.05),而在心脏中的分布明显低于Taxol组(P<0.05)。结论:紫杉醇自组装前体脂质体与市售注射液相比,大鼠体内配置发生明显变化,特别是提高紫杉醇在肝、脾、卵巢、子宫的药物分布同时降低心脏的分布,对于临床更好地治疗肝脾部、卵巢、子宫癌症和降低心脏毒性具有现实意义。
Aim： To study in vivo biodistribution of paclitaxel self-assembled proliposomes （PSAP） in rats by LC-MS/MS and to evaluate its targeting performance in conparison to Taxol. Methods： LC-MS/MS method based on positive electrospray ionization （ESI^＋-MS/MS） has been developed for quantifying paclitaxel in rat tissue homogenates. PSAP and Taxol were administered through tail vein at the dose of 5 mg/kg body weight and seven tissues have been excised and processed properly at preplanned time intervals to quantitate PTX by LC-MS/MS for evaluation of biodistribution and targeting performance. Results： In comparison with the Taxol group, paclitaxel levels in the liver, spleen, ovary, uterus were significantly higher in the PSAP group than that of in the Taxol group（ P 〈 0.05）. Relative tissue exposure（re） was greater than 1 in those above-mentioned tissues in the PSAP group. Paclitaxel distribution in the lung and kidney showed no significant difference （ P 〉 0. 05） between these two groups though paclitaxel level in the heart was significantly lower in the PSAP group than that in the Taxol group （ P 〈 0. 05）. Conclusion： Significant change of drug disposition in vivo could be found when iv PSAP to rats in comparison to Taxol. Especially,PSAP could improve drug distribution in the liver, spleen, ovary, and uterus and lower that in the heart, which could be expected to yield better antitumor clinical therapy of tumor in the liver and spleen, hysterocarcinoma and ovarian cancers.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2006年第4期318-322,共5页
Journal of China Pharmaceutical University
