道诺霉素脂质体玻璃体内代谢及视网膜毒性

Liposome-encapsulated Daunomycin and Its Clearance from the Vitreous and Tcxicity to the Retina

采用逆相蒸发法制备了道诺霉素脂质体,测得脂质体包裹率为31.6%,终浓度为100μg/ml,直径为60～125nm。用荧光分光光度法在24只兔进行了道诺霉索及其脂质体玻璃体内药物清除率测定。18只兔用于ERG、光镜和透射电镜检查以评价药物的视网膜毒性。结果道诺霉素在玻璃体内的半衰期为145.5min;道诺霉素脂质体在眼内的头两天清除较快,但在14d仍可测出平均浓度为0.64μg/ml。电镜观察表明道诺霉素剂量超过5μg,或其脂质体超过20μg出现光感受器毒性。提示道诺霉素脂质体能明显延长有效浓度时间并减低眼内毒性反应。

We prepared daunomycin encapsulated in liposomes (DL) by modified reverse-phase evaporation with an encapsulation rate of 31.6%, final concentration of 100 μg/ml and the diameter of 60-125nm. Twenty-four rabbits were used for measurements of the clearance of daunomycin (Dm) and DL from the vitreous by a spectrophotofluorometer. ERG and light and electron microscopies were made to evaluate the toxicity of Dm and DL to the retina in 18 rabbits. The halftime of Dm cleared from the vitreous was 145.6 min. Clearance of daunomycin encapsulated in liposomes was rapid during the first 2 days and the concentration was 0.64 μg/ml 14 days after injection. Electron microscopy showed that Dm at a dosage of over 5μg or DL over 20 μg was toxic to the photoreceptors of the retina. The results suggest that DL can prolong an effective drug level in the vitreous and reduce toxicity to the retina.