ENGINEERED ALGINATE MICROCAPSULES FOR MOLECULAR THERAPY TROUGH BIOLOGIC SECRETING CELLS

Continuous delivery of monoclonal antibodies (mAbs) at low concentrations may be helpful in the management of several chronic, especially autoimmune diseases. A possible approach to employ mAbs therapy in vivo, in absence of in vitro manipulations, could be graft of microcapsules containing mAb-secreting hybridoma cells (HY). Sodium Alginate (AG) is a polymeric saccharide that permits simple fabrication of microcapsules that are biocompatible and prevent immune recognition of encapsulated cells, upon graft, by the host's immune system. However, at present, AG-based microcapsules are usually impermeable to large molecules. The aim of this study was to engineer the membrane of AG-based microcapsules, to make it permeable to larger molecular weight classes of mAbs. To this end, we have prepared a new AG-based membrane, using standard reagents already in use, but following different coating procedures and molar ratios. In particular, we fabricated a new capsular membrane permeable to IgM synthesized by the HY cell line G3C. Morphologic structural and ultrastructural analysis of the new membranes before and after intra peritoneal transplant, in conjunction with IgM outflow secretory kinetics underwent both, in vitro and in vivo assessment. While allowing immunoprotection of the enveloped HY, as demonstrated by the absence of any inflammatory response, the microcapsules permitted G3c mAb egress, on a regulated delivery kinetics. HY viability persisted, upon transplant, for long time periods. In summary, the new AG-based microcapsules allow delivery of big molecules out of the capsules, while protecting the enveloped HY from the host's immune system. These microcapsules could apply to implant cells producing fully active large molecules without the need of time- and cost expensive procedures to purify them.