Kinetics of protein diffusion from a poly(D,L-lactide) reservoir system.

The release kinetics of albumin diffusion from a poly(D,L-lactide) reservoir system was investigated with the long-term aim of developing a multidose pulsatile delivery system. Albumin pellets were coated with polylactide of varying viscosity-average molecular weight, Mv, and concentration, and incubated in aqueous solution. The albumin release profile was approximated by zero-order release kinetics, with release rates ranging from 3 to 1800 mg/day. The permeability of the poly(D,L-lactide) membranes to albumin diffusion ranged from 1 x 10(-9) to 100 x 10(-9) cm2/S, and was found to decrease with increasing membrane thickness (18 to 1400 microns) and density (300 to 3000 mg/cm3). The initiation of albumin release from the pellets could be delayed from a few hours to more than one month by increasing the Mv of the polylactide from 6.2 x 10(3) to 140 x 10(3) and raising the concentration of the polymer coating solution from 50 to 100 mg/mL. The diversity in delayed-release effect and the variations in membrane permeabilities were attributed to changes in membrane porosity and polymer morphology.