脂质体载药降低阿霉素毒性的实验研究

 目的：研究阿霉素(F-ADM)和脂质体阿霉素(L-ADM)对正常NIH小鼠和肝癌腹水型(HcAC)小鼠的毒性。方法：采用卵磷脂、磷脂酸和胆固醇，应用冰冻融解法制成多层脂质体。NIH小鼠分为阿霉素和脂质体阿霉素两组。每组分为7.5,15,20和30 mg/kg 4个对应剂量组，尾静脉给药，观察60 d。NIH小鼠腹内接种HcAC 96 h后分为阿霉素和脂质体阿霉素两组，每组分为9,15和20 mg/kg 3个对应剂量组，腹腔内给药。结果：脂质体组动物体重和器官失重明显减轻；血生化变化相对减小；外周血白细胞下降幅度减小，恢复加快；心、肾、胃肠道病理损害减轻；药物的LD₅₀从14.7 mg/kg提高到21.9 mg/kg。在接种肿瘤96 h的延迟治疗组，动物对药物的耐受性下降，毒性死亡率升高。而脂质体组仍有较好疗效，生存期有所延长。结论：脂质体载药后可降低阿霉素的毒性并保留药物的抗肿瘤活性。

An experimental study on lowered toxicities of adriamycin with liposome encapsulation in mice

OBJECTIVE:To study the toxicities of free adriamycin(F ADM) and liposome entrapped adriamycin(L ADM).METHOD:The large multilamellar liposomes,containing phosphotidylcholine,phosphotidic acid and cholesterol,were prepared by a freeze thawing method.The NIH mice were divided into F ADM or L ADM groups.There were four doses groups with 7.5,15,20 and 30 mg/kg respectively in F ADM or L ADM groups.The drugs were injected through the tail vein and were observed for 60 days.Having been inoculated with hepatocellular ascites carcinoma(HcAC) cells for 96 hours,the mice were also divided into F ADM or L ADM groups.The drugs were injected(ip).There were three different doses groups with 9,15 and 20 mg/kg respectively.RESULTS:With L ADM,the losses of animal body and organ weight,the reduction of the white blood cells,the pathological damages as cardiotoxicity,nephrotoxicity and gastroenterotoxicity were less than those with F ADM.LD 50 of drug was increased about 0.49 time after liposome entrapped the drug.After the mice were inoculated with tumor for 96 hours,the drug toleration of the mice was significantly lowered.Liposome agent could effectively protect against lathal toxicities of the drug in these mice.CONCLUSION:The liposome agent could reduce toxicities and remain its antitumor effect of adriamycin.