Edman P, Sjöholm I
J Pharm Sci. 1982 May;71(5):576-80. doi: 10.1002/jps.2600710523.
L-Asparaginase was immobilized in microparticles of polyacrylamide. Such particles were then injected by intramuscular/subcutaneous, intraperitoneal, or intravenous routes into mice to investigate the immunological consequences of the immobilization. Entrapment of L-asparaginase in microparticles did not prevent the formation of antibodies in intensively treated animals. Intraperitoneal and intravenous injections of particles produced significantly higher antibody levels than soluble L-asparaginase. Antigen administered intramuscularly/subcutaneously in microparticles elicited, however, a weak immune response. Dependent on the route of administration, the particles may thus function as an adjuvant. A modified Arthus reaction in the foot pads of immunized mice indicated that antigenicity decreased when L-asparaginase was immobilized in microparticles. Injection of free L-asparaginase, intramuscularly/subcutaneously (2 x 20 IU) in the preimmunized mice produced no effects on the serum level of L-asparagine, whereas intramuscular/subcutaneous injection of L-asparaginase in microparticles produced a depression of the serum concentration. It is concluded that the intramuscular/subcutaneous injection of L-asparaginase in microparticles is the choice route of administration with respect to duration and the immunological reaction.
L-天冬酰胺酶固定于聚丙烯酰胺微粒中。然后通过肌内/皮下、腹腔内或静脉内途径将此类微粒注射到小鼠体内,以研究固定化的免疫学后果。L-天冬酰胺酶包埋于微粒中并未阻止经过强化治疗的动物体内抗体的形成。腹腔内和静脉内注射微粒产生的抗体水平显著高于可溶性L-天冬酰胺酶。然而,肌内/皮下注射微粒中的抗原引发的免疫反应较弱。因此,根据给药途径的不同,微粒可能起到佐剂的作用。免疫小鼠足垫的改良阿瑟斯反应表明,当L-天冬酰胺酶固定于微粒中时,其抗原性降低。在预先免疫的小鼠中肌内/皮下注射游离L-天冬酰胺酶(2×20 IU)对血清中天冬酰胺水平没有影响,而肌内/皮下注射微粒中的L-天冬酰胺酶会导致血清浓度降低。得出的结论是,就持续时间和免疫反应而言,肌内/皮下注射微粒中的L-天冬酰胺酶是首选的给药途径。