脂质体载药降低阿霉素抗SRS淋巴瘤毒性的实验研究

DECREASED TOXICITY OF EFFECT OF ADRIAMYCIN ON LYMPHOMA-BEARING MICE BY LIPOSOMES AS DRUG CARRIERS

本文将阿霉素包封在多层脂质体中,观察治疗SRS淋巴瘤小鼠的毒性反应。与游离阿霉素比较,脂质体阿霉素能明显降低小鼠的早期死亡率,骨髓抑制作用减轻。通过血液生化检测与心、肝组织的病理观察,结果表明脂质体载药后能明显降低阿霉素治疗SRS淋巴瘤小鼠的毒副作用。

Adriamycin was encapsulated in multivesicular liposomes which composed of egg lipids. The toxic reaction of the encapsulated adriamycin was compared with that of free adriamycin (F-ADM) at equal doses in mice bearing SRS lymphoma. The resuled showed that encapsulation of adriamycin into liposomes (L-ADM) resulted in marked increase of the value of LD50 and decrease of myelosuppression. At the same dose of 15 mg / kg, F-ADM and L-ADM had 4-6 fold and less than threefold increase of the value of serum GPT and GOT of SRS lymphoma bearing mice respectively as compared with that of the control. Light microscopic examination of cardiac and hepatic sections taken from SRS lymphoma-bearing mice receiving 15 mg/kg F-ADM observed noticeable histologic changes on day 3, and by day 7 the cardiac and hepatic damage became severe. Cellular edema, monocyte infiltration, and cell necrosis were evident. Hyperplasia of Kupffer's cells also found in hepatic sections. In contrast, in sections taken from mice receiving same dose of L-ADM only slight edema and no cell necrosis was demonstrated by day 7. Ultrastructurally, in cardiac sections, the loss of cytoplasmic elements, swelling and distortion of mitochondria, extensive vacuolization and lysis of myofilament especially near vascular beds were noted on mice treated by F-ADM. Focal cellular swelling and fragmental loss of myofilament were observed on mice treated by L-ADM. It was suggested that the toxicity of adriamycin encapsulated in liposomes on SRS lymphoma-bearing mice decreased markedly.