脂质体载药减少阿霉素心脏毒性的实验研究

目的：研究阿霉素（Ｆ－ＡＤＭ）和脂质体阿霉素（Ｌ－ＡＤＭ）对ＮＩＨ小鼠的心脏毒性。方法：采用卵磷脂、磷脂酸和胆固醇制备多层脂质体。实验动物分为阿霉素组和脂质体阿霉素组。其中１ｍｇ·ｋｇ－１对应剂量组观察药物分布；７．５、１５和２０ｍｇ·ｋｇ－１对应剂量组观察药物毒性。结果：用药后４和２４ｈ心肌内药物浓度分别为：阿霉素组８．６１、４．１１μｇ·ｇ－１，脂质体阿霉素组２．５３、０．９８μｇ·ｇ－１。阿霉素１５ｍｇ·ｋｇ－１组５例动物中Ⅲ级以上心肌损害４例，而脂质体阿霉素组无Ⅲ级以上损害。且心、肝、肾病理损害明显减轻。结论：含负电荷磷脂的脂质体载药后可明显减轻阿霉素对心肌的毒性损害。

Liposomes as carrier of adriamycin in vivo: reduced cardiac toxicity in mice

AIM: To study the cardiac toxicity of free adriamycin (F AMD) and liposomes entrapped adriamycin (L ADM). METHODS: The multilamillar liposomes containing phosphatidycholine, phosphatidic acid and cholesterol was used. The NIH mice were divided into F ADM or L ADM groups. There were four different dose levels (1, 7 5, 15 and 20 mg·kg -1 in every group. The tissue drug concentrations were investigated at a dose of 1 mg·kg -1 . The toxicities of F ADM and L ADM were compared to other dose groups. RESULTS: The drug concertration of cardiac tissue in 4 and 24 h with the F ADM were 8 61 and 4 11 μg·g -1 , respectively, whereas they were only 2 53 and 0 98 μg·g -1 with the L ADM. In the F ADM group, there were four cases out of 5 mice showing histologic evidence of cardiotoxicity at Grade Ⅲ over, whereas no damage at Grade Ⅲ occurred in any cases with the L ADM group. Compared with the F ADM, the L ADM significantly reduced the histopathological lesions in the tissues of the heart, liver and kidney. CONCLUSION: The adriamycin entrapped in negative charged liposomes could effectively reduce the drug toxicity for cardiac tissue.