Control and enhancement of permselectivity of membrane-based microcapsules for favorable biomolecular transport and immunoisolation

Abstract

The success of membrane-based, cell-encapsulating microcapsules depends on the membrane permselectivity that provides efficient inward transport of nutrients, therapeutic protein egress, and complete exclusion of immunoglobulins. Microcapsules with a calcium crosslinked alginate core and a genipin-crosslinked chitosan alginate (GCA) were prepared with good control over size, membrane thickness and density. Importantly, in this study, we report a novel approach of using three relevant biomolecules and investigating the effects of the membrane characteristics (thickness and density) and microcapsule size on biomolecular mass transport across the GCA microcapsules using mathematical models based on a balance of the chemical potential. Scaling analysis was used to interrelate the membrane thickness, chitosan–alginate reaction rate constant, and diffusion coefficient. The resistance to diffusion of the three biomolecules increased with membrane density and thickness. Interestingly, swelling in the large microcapsules resulted in an increase in permeability, allowing larger biomolecules (immunoglobulin and carbonic anhydrase) to diffuse more readily. In the case of the smaller biomolecule, vitamin B₁₂, a shorter diffusion path length in smaller microcapsules allowed better ingress. When compared with other microcapsules, the GCA microcapsules possess improved permselectivity for them to allow diffusion of small nutrient molecules and proteins, whereas completely excluding antibodies. Also, these results elucidate the importance of membrane properties and microcapsule size to realize favorable transport of biomolecules. © 2011 American Institute of Chemical Engineers AIChE J, 2011