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

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

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 3 7℃小牛血清及 3 7℃ ,2 0℃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 3 7℃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 ( 2 3 3hvs 12 0h)。

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℃ and in phosphate buffer solution (PBS) at 37℃, 20℃ and 4℃. 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℃. 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.