氢化与非氢化卵磷脂对阿霉素脂质体体内外稳定性的影响

目的研究卵磷脂(EPC)和氢化卵磷脂(HEPC)对阿霉素脂质体的体外泄漏及体内循环时间的影响.方法用透析法考察EPC及HEPC普通脂质体在37℃小牛血清及37℃,20℃和4℃PBS中的药物泄漏情况;用高效液相色谱法研究了EPC和HEPC长循环脂质体在大鼠体内的药物动力学.结果在37℃小牛血清中HEPC脂质体较EPC脂质体泄漏慢,而在PBS中则结果相反;大鼠体内药物动力学研究结果表明,HEPC长循环脂质体在血中的平均驻留时间(MRT)较EPC长循环脂质体长得多(23.3h vs 12.0h).结论HEPC长循环脂质体是靶向血管外部位的更好的药物载体.

EFFECTS OF DIFFERENT PHOSPHOLIPIDS ON THE STABILITIES OF DOXORUBICIN LIPOSOMES IN VITRO AND IN VIVO

AIM: To study the effects of egg phosphatidylcholine (EPC) and hydrogenated egg phosphatidylcholine (HEPC) on the leakage of doxorubicin liposome in vitro and the resident time in blood. METHODS: By the means of dialysis, the leakage of EPC (EPC-NL) and HEPC normal liposomes (HEPC-NL) in fetal cattle serum (FCS) was determined at 37 degrees C and in phosphate buffer solution (PBS) at 37 degrees C, 20 degrees C and 4 degrees C. Furthermore, the pharmacokinetics of EPC and HEPC sterically stabilized liposomes (EPC-SSL and HEPC-SSL) were studied by HPLC. RESULTS: The leakage of doxorubicin from HEPC-NL is slower than that of EPC-NL in FCS at 37 degrees C. But in PBS at all of three different temperatures, the results are completely reversed, i.e., the leakage of EPC-NL is slower than that of HEPC-NL. Further studies on pharmacokinetics showed that the mean residence time of HEPC-SSL in blood is 23.3 h, while that of EPC-SSL is 12.0 h, and the area under the curve (AUC) of concentration of HEPC-SSL is larger than that of EPC-SSL. CONCLUSION: HEPC-SSL is a better carrier in delivering the drugs to the extravascular sites than EPC-SSL.