Water Soluble Polymers for Immunoisolation II: Evaluation of Multicomponent Microencapsulation Systems

Microcapsules have been prepared via a complex coacervation reaction from polyanion and polycation mixtures. Multicomponent blends of synthetic, semi-synthetic and naturally occurring macromolecules have been evaluated with a particular interest in the preparation of immunoisolation barriers for pancreatic islets. A screening has resulted in thirty three polymeric systems which have been compared according to their mechanical strength, capsule characteristics (such as shape, surface smoothness, stability, and swelling/shrinking) and permeability (MWCO). A limited number of tests were also carried out on the cell viability in the presence of polymer mixtures. These included measurements of the perifusion of encapsulated pancreatic islets and the host tissue response. The quality of the membrane produced was observed to be a strong function of the polymer properties, processing conditions, such as the type and concentration of the simple electrolyte, and the reaction time. Additionally, a multicomponent polyelectrolyte technology based on the formation of a capsular “wall-complex” was developed for the simultaneous optimization of the membrane mechanical properties and permeability. This involved the preparation of a wide pore matrix through the reaction of a core polyanion with a small ionotropic ion. A second, low or medium molecular weight, polycation was subsequently added, in a second reactive stage, and its time dependent diffusion into the capsule could be used to control the membrane wall thickness and permeability. Alternatively, the simultaneous application of low and high molecular weight cations (or a divalent and polyvalent cation) often led to capsules with similar controllable properties. For many combinations, a distinct capsular wall was observed. Overall seven chemistries were identified as providing suitable permeability and capsular mechanical properties. All contained an anionic polysaccharide blend interior to an oligocation solution. The alginate/cellulose sulfate//polymethylene-co-guanidine/calcium chloride/sodium chloride system was found to be the most viable alternative to the standard alginate-polylysine-alginate capsule (APA).