Jr. Hwang et Mv. Sefton, EFFECT OF CAPSULE DIAMETER ON THE PERMEABILITY TO HORSERADISH-PEROXIDASE OF INDIVIDUAL HEMA-MMA MICROCAPSULES, Journal of controlled release, 49(2-3), 1997, pp. 217-227
Poly (2-hydroxyethyl methacrylate-methyl methacrylate), (HEMA-MMA) mic
rocapsules to be used for the transplantation of live mammalian cells
were prepared by an interfacial precipitation process. ii submerged je
t coextrusion technique was used to make various sizes of capsules as
small as 450 mu m in outside diameter. A novel method based on an enzy
me-chromogenic substrate assay was used to measure the capsule permeab
ility at the individual capsule level. Capsule size, shearing frequenc
y (number of capsules sheared per unit time), capsule permeability and
the capsule-to-capsule variation in permeability were dependent, dire
ctly or indirectly, upon the shearing force (i.e. hexadecane flow-rate
) applied to the nozzle during preparation. The average permeability c
oefficients of those capsules to horseradish peroxidase, (HRP, MW 40kD
a, a model protein), were in the range of 2x10(-10) to 9x10(-10) cm(2)
/sec; the permeability varied from 1x10(-10) to 3x10(-10) cm(2)/s for
500 mu m capsules (the best) and 0.1x10(-10) to 6x10(-10) cm(2)/s for
660 mu m capsules (the poorest). Scanning electron microscopy illustra
ted that finger-like macrovoids were formed under the external skin la
yer of the capsule membrane, but that an interconnected open-cell stru
cture was formed under the internal skin. Modelling the precipitation
process in two dimensions (i.e. between two glass slides) suggested th
at the faster precipitation of HEMA-MMA at the external surface domina
ted the formation of the membrane structure, compared with the slower
precipitation at the internal surface. (C) 1997 Elsevier Science B.V.