Effect of capsule diameter on the permeability to horseradish peroxidase of individual HEMA-MMA microcapsules

Abstract

Poly (2-hydroxyethyl methacrylate-methyl methacrylate), (HEMA-MMA) microcapsules to be used for the transplantation of live mammalian cells were prepared by an interfacial precipitation process. A submerged jet coextrusion technique was used to make various sizes of capsules as small as 450 μm in outside diameter. A novel method based on an enzyme-chromogenic substrate assay was used to measure the capsule permeability at the individual capsule level. Capsule size, shearing frequency (number of capsules sheared per unit time), capsule permeability and the capsule-to-capsule variation in permeability were dependent, directly or indirectly, upon the shearing force (i.e. hexadecane flow-rate) applied to the nozzle during preparation. The average permeability coefficients of those capsules to horseradish peroxidase, (HRP, MW 40kDa, a model protein), were in the range of 2×10 −10 to 9×10 −10 cm 2/sec; the permeability varied from 1×10 −10 to 3×10 −10 cm 2/s for 500 μm capsules (the best) and 0.1×10 −10 to 6×10 −10 cm 2/s for 660 μm capsules (the poorest). Scanning electron microscopy illustrated that finger-like macrovoids were formed under the external skin layer of the capsule membrane, but that an interconnected open-cell structure was formed under the internal skin. Modelling the precipitation process in two dimensions (i.e. between two glass slides) suggested that the faster precipitation of HEMA-MMA at the external surface dominated the formation of the membrane structure, compared with the slower precipitation at the internal surface.