Delivery of fungal beta-galactosidase to rat brain by means of liposomes.
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.
D000818:Animals; D000908:Antibodies, Fungal / Q000032:analysis; D001230:Aspergillus / Q000201:enzymology*; D001236:Aspergillus oryzae / Q000201:enzymology* / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005260:Female; D005696:Galactosidases / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000908:Antibodies, Fungal; D008081:Liposomes; D005696:Galactosidases