摘要
目的本文研究不同相对分子质量的聚乙二醇(PEG)溶解7-乙基-10-羟基喜树碱(7-ethyl-10-hydroxycamptothecin,SN-38)对其体外稳定性以及小鼠淋巴摄取量的影响。方法体外实验在SN-38的pH值7.4的PBS饱和溶液中分别加入乙醇、PEG200、PEG400、PEG800,37℃水浴12 h,用HPLC测定SN-38含量;在体内实验中分别将SN-38用乙醇及含体积分数50%PEG200-800的乙醇溶液配制成质量浓度为1 g·L-1的SN-38溶液剂,将上述SN-38的溶液剂在小鼠右后脚掌皮下注射,剂量为1 mg·kg-1。给药后分别于不同时间点用HPLC测定小鼠淋巴结及脚掌中的SN-38的含量。结果体外的稳定性实验测得SN-38含量为PEG200组>PEG400组>PEG800组>乙醇组;乙醇组与PEG200-800组小鼠淋巴结中药物的含量结果与体外稳定性结果一致。结论 PEG能够稳定SN-38的内酯环从而增强SN-38的淋巴摄取量,并且随着PEG相对分子质量的增加,这种稳定作用减弱。
Objective To study the effect of different molecular weight poly(ethylene glycol)(PEG) on in vitro stability of 7-ethyl-10-hydroxycamptothecin(SN-38) and lymphatic uptake in mice after subcutaneous administration. Methods To investigate the stability in vitro, after addition of ethanol, PEG200, PEG400, PEG800 to saturated solution of SN-38 in pH 7.4 PBS individually, the solutions were maintained at 37 ℃ in waterbath for 12 h, then the concentration of SN-38 was determined with HPLC;for the in vivo study, SN-38 was dissolved in ethanol and ethanol solution containing 50% PEG200-800 with the concentration of 1 g·L-1, respectively. The above SN-38 solutions were administrated into the right soles of mice subcutaneously at the dose of 1 mg·kg-1. Then, the concentrations of SN-38 at different time points were detected with HPLC. Results The stability study show that the concentrations of SN-38 in different PEG solutions were in the order of PEG200>PEG400>PEG800>ethanol, and the concentrations of SN-38 in the popliteal lymph nodes of mice for different solutions were in accordance with the result in vitro. Conclusion PEG can stabilize the lactone ring of SN-38 and enhance the lymphatic uptake of SN-38.
出处
《中国药剂学杂志（网络版）》
2014年第2期62-72,共11页
Chinese Journal of Pharmaceutics：Online Edition
关键词
药剂学
7-乙基-10-羟基喜树碱
聚乙二醇
皮下给药
内酯环稳定性
淋巴摄取
pharmaceutics
7-ethyl-10-hydroxycamptothecin
poly(ethylene glycol)
subcutaneously administration
stability of the lactone ring
lymphatic uptake
