Takada G, Onodera H, Tada K
Tohoku J Exp Med. 1982 Feb;136(2):219-29. doi: 10.1620/tjem.136.219.
A significant increase in beta-galactosidase activity was observed in the brain of rats 1 hr after an intravenous injection of liposomes containing beta-galactosidase purified from Aspergillus oryzae. The increased activity was proved to have features of the fungal enzyme by differentiating it from rat's native beta-galactosidase in both heat stability and immunochemical studies. Blood content of rat brain tissue under the experimental conditions employed was estimated as 0.83% (v/w) from an infusion experiment of 131I-labeled human serum albumin. The net uptake of fungal beta-galactosidase by rat brain was calculated as equal to 10 micrograms protein of the fungal enzyme or 0.31% of the injected dose/g tissue, which gave rise to 4.4-fold net increase in enzyme activity above control levels. The experiments clearly demonstrated that liposome-entrapped fungal enzyme was allowed to penetrate the blood-brain barrier and to gain access to rat brain, suggesting liposomes as an effective carrier for exogenous enzyme delivering to the central nervous system of patient with inherited lysosomal storage diseases.
静脉注射含有从米曲霉中纯化得到的β-半乳糖苷酶的脂质体1小时后,在大鼠大脑中观察到β-半乳糖苷酶活性显著增加。通过在热稳定性和免疫化学研究中将其与大鼠天然β-半乳糖苷酶区分开来,证实增加的活性具有真菌酶的特征。根据131I标记的人血清白蛋白的输注实验,在所采用的实验条件下,大鼠脑组织的血液含量估计为0.83%(体积/重量)。大鼠大脑对真菌β-半乳糖苷酶的净摄取量经计算相当于10微克该真菌酶蛋白,或每克组织注射剂量的0.31%,这使得酶活性比对照水平净增加了4.4倍。这些实验清楚地表明,脂质体包裹的真菌酶能够穿透血脑屏障并进入大鼠大脑,这表明脂质体作为一种有效的载体,可用于将外源性酶递送至患有遗传性溶酶体贮积病的患者的中枢神经系统。