The in vivo Effects of Semipermeable Microcapsules containing L-Asparaginase on 6C3HED Lymphosarcoma

Abstract

SEMIPERMEABLE microcapsules are spherical ultrathin polymer membranes of cellular dimensions each enveloping a micro-droplet of protein solution or suspension^1,2. Microencapsulated enzymes, while prevented from leaking out to give rise to hypersensitivity or immunological reactions, can act on external substrates dialysing across the semipermeable membranes^3,4. Microencapsulated enzymes include those present in erythrocyte haemolysates, urease, catalase, trypsin, uricase and L-asparaginase^1,4. L-Asparaginase suppresses the growth of certain asparagine dependent tumours⁵ by depleting the extracellular supply of asparagine. Recent reviews^6–9 suggest that parenterally injected Escherichia coli asparaginase is removed rapidly as foreign protein and that there appears to be a relationship between the antitumour activity and the plasma half-life of L-asparaginase. In addition, E. coli asparaginase may give rise to hypersensitivity and immunological reactions. Because microencapsulated L-asparaginase acts efficiently in vitro and in vivo on asparagine which dialyses across the microcapsule membranes¹⁰, we have examined the effects of microencapsulated asparaginase on 6C3HED lymphosarcoma cells implanted in mice.