Biodegradable microspheres. I. Duration of action of dextranase entrapped in polyacrylstarch microparticles in vivo.
Dextranase was entrapped in polyacryl starch microspheres of different compositions by emulsion polymerization. After i.v. injection in mice and rats, the particles were removed from the blood circulation by macrophages of the reticuloendothelial system. In these cells, the particles are accumulated in the lysosomes. The degradation of different 14C-labeled microparticles and their entrapped dextranase was followed in an isolated lysosomal fraction in vitro and in liver and spleen after i.v. injection in mice. The duration of entrapped dextranase in vivo was followed directly, i.e., by an enzyme assay, and indirectly by following the decrease of a stored material, [3H]dextran in the liver. The degradation of the entrapped enzyme was dependent on the composition of the particle matrix. More cross-linked spheres could better protect the entrapped enzyme in vitro and in vivo. The half-life of free dextranase in the lysosomal fraction was estimated to be about 4 hr, whereas the duration of entrapped dextranase in the liver was at least 48 hr, as measured with [3H]dextran. Finally, the effect of entrapped and free dextranase on an artificially induced storage disease was studied. The stored [3H]dextran was eliminated completely when dextranase was used in microparticles, whereas free dextranase had no effect in vivo.
D000818:Animals; D002250:Carbon Radioisotopes; D003910:Dextranase / Q000008:administration & dosage / Q000494:pharmacology*; D004355:Drug Stability; D004800:Enzymes, Immobilized / Q000494:pharmacology*; D006207:Half-Life; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008863:Microspheres; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013213:Starch / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism; D013997:Time Factors
D002250:Carbon Radioisotopes; D004800:Enzymes, Immobilized; D013213:Starch; C043831:starch polyacrylate; D003910:Dextranase