CONTROL AND MEASUREMENT OF PERMEABILITY FOR DESIGN OF MICROCAPSULE CELL DELIVERY SYSTEM

Transplantation of immunoisolated islets of Langerhans has been propos ed as a promising approach to treating insulin-dependent diabetes mell itus. Recently, a cell delivery system based on a multicomponent micro capsule has been designed for the immunoisolation of insulin-secreting pancreatic islets. The capsule, formed by polyelectrolyte complexatio n of sodium alginate and cellulose sulfate with poly(methylene-co-guan idine), markedly has improved mechanical strength compared with the wi dely used alginate/poly(L-lysine) capsules. It also provides a flexibi lity for readily adjusting membrane thickness and capsule size, and, m ore important, the membrane permeability can be altered over a wide ra nge of molecular sizes. To rigorously test the capsule diffusion prope rties, we have improved capsule permeability measurement by using two complementary methods: (1) size exclusion chromatography with dextran standards; and (2) newly developed methodology for assessing permeabil ity to a series of biologically relevant proteins. Viability and funct ion of rat pancreatic islets enclosed in the capsules with different p ermeability were tested in vitro. The insulin secretion of encapsulate d islets was well preserved even though slightly delayed in comparison with a control group of free islets. We believe that the unique featu res of this encapsulation system together with the precise characteriz ation of its physical parameters will enable us to find the optimal ra nge of capsule permeability for in vitro and in vivo survival and func tion of encapsulated pancreatic islets. (C) 1998 John Wiley & Sons, In c.