Alginate Polylysine Microcapsules as Immune Barrier: Permeability of Cytokines and Immunoglobulins over the Capsule Membrane

Abstract

Transplantation of pancreatic islets in alginate polylysine microcapsules is a potential useful method for treating type I diabetes. In this study, the permeability for alginate-polylysine microcapsules to cytokines an immunoglobulines has been investigated by a newly developed method. Magnetic monodisperse polymer particles (Dynabeads) coated with antibodies against selected proteins were encapsulated in 0.7 mm alginate polylysine microcapsules. The capsule membrane permeability to IgG (150 kDa). Transferrin (81 kDa), Tumor necrosis factor (TNF, 51 kDa), Interleukin-1β (IL-1β, 17.5 kDa), and insulin (5.8 kDa) was estimated by measuring the binding of 125I-labeled proteins to the encapsulated antibody coated Dynabeads. Capsules with an inhomogeneous solid gel core were made of alginates with high guluronic or high mannuronic acid content and poly-l (PLL)- or poly-d-lysine (PDL) of concentrations varied from 0.05-0.2%. The various capsules examined were all impermeable to IgG. The capsules made with a PLL-, but not PDL-membranes were permeable for transferrin. IL-1β was found to penetrate all of the different capsule types. The high-G capsules, however, could be made impermeable to TNF and still allowed transferrin to pass. The permeability of these capsules to IL-1β, but not to TNF was confirmed in an assay where mouse islets of Langerhans were incubated with TNF and IL-1β, and comparing the IL-6 for encapsulated and non-encapsulated islets.