Use of immobilized L-asparaginase in acrylic microparticles in an extracorporeal hollow-fiber dialyzer.

L-asparaginase was immobilized under aseptic conditions in spherical microparticles of polyacrylamide. To avoid direct contact between blood and enzyme, we have applied the immobilized L-asparaginase in microparticles on the outer surface of the capillary fibers of a hemofilter. The hemofilters were very efficient in the transformation of L-asparagine to L-aspartic acid, both in vitro and in vivo. L-Asparagine in buffer (50 microM in 5 liters) was converted to L-aspartic acid within 60 min after circulation through a hemofilter containing 2000 I.U. of L-asparaginase. Circulating L-asparagine in healthy sheep (about 40-50 microM was reduced to low levels after 2 to 3 hr of perfusion with a unit containing 2000 I.U. of L-asparaginase. The reduction persisted for 3 to 4 hr after terminated treatment. Repeated, extracorporeal treatments in sheep showed that the L-asparagine decrease induced an increased resynthesis of L-asparagine, probably due to the action of the L-asparagine synthetase.