STUDIES ON SMALL (LESS-THAN-300 MU-M) MICROCAPSULES .2. PARAMETERS GOVERNING THE PRODUCTION OF ALGINATE BEADS BY HIGH-VOLTAGE ELECTROSTATICPULSES

The size of microcapsules is a critical parameter in the immunoisolati on of islets of Langerhans by microencapsulation. The use of smaller c apsules decreases the total implant volume and improves insulin kineti cs and oxygen supply. A high voltage electrostatic pulse system was us ed for the production of small (<300 mu m) alginate beads, the first s tep of the encapsulation technique. However, islets often protruded fr om capsules that were too small, further emphasizing the need for a me thod to control bead size. A study of 7 parameters [electrostatic puls e amplitude (A), duration (D) and wavelength (lambda), pump flow rate (P), needle gauge, alginate viscosity and distance between electrodes] showed that P (r = 0.981, p = 0.003) and lambda (r = 0.988, p = 0.000 2) were the principal determinants of bead size. To detect potential i nteractions between parameters, 270 combinations of different levels o f A, D, lambda, and P were studied. A multivariate regression analysis of these data confirmed that P and lambda are the prime determinants of bead size, and showed that a 2-parameter (P, lambda) model could be used to precisely predict bead size (R(2) = 0.84), while keeping the application simple. The precision of the predictive model is only slig htly improved by the use of additional parameters. The reliability of the data used to elaborate this model was demonstrated (p = 0.6226) by comparing them with a second data set obtained under the same conditi ons. A third set of experiments confirmed the applicability of the mod el. This work has major implications on the preclinical application of microencapsulation since it showed that it is possible to predetermin e the bead size.