Development of novel drug delivery system of bioactive molecules from “cytomedicine” using hybridoma cells entrapped in alginate-poly(L)lysine-alginate microcapsules

Abstract

The controlled release of biologically active molecules by the living cells, which have various functions including regulation by sensor, biosynthesis and secretion of active proteins, is the ideal of drug delivery systems (DDS). The implantation of the living cells without graft rejection would enable delivery of the bioactive molecules produced by the cells for a long time in vivo. We have developed to novel DDS “cytomedicine” using living cells entrapped in alginate-poly(L)lysine-alginate (APA) microcapsules which has a selective semipermeable characteristic. Because the APA membrane allows small molecules such as glucose and nutrients to diffuse freely but prevents the passage of large molecules and cells, entrapped cells are isolated from the host's immune system. In this study, we examined the effects of molecular weight of poly(L)lysine on the properties of APA microcapsules and viability of entrapped cells in vitro. Moreover, cytomedical therapeutic effects of APA-microencapsulated SK2 hybridoma cells (APA-SK2 cells), which secrete the anti-human interleukin 6 (hIL-6) antibody, were examined using hIL-6 transgenic mice (hIL-6 Tgm). Single i. p. injection of APA-SK2 cells improved IgG1 plasmacytosis and mesangio-proliferative glomerulonephritis in hIL-6 Tgm. This indicated that the cytomedicine is very effective for long-term delivery of bioactive molecules in vivo.