Morphological changes in degrading PLGA and P(DL)LA microspheres: implications for the design of controlled release systems

Abstract

The in vitro degradation of microspheres of polymers of lactic and glycolic acids were investigated by monitoring the mass loss from the device, the molecular weight of the polymer and the morphological changes of the particles with time. Two different sequences of morphological changes were found to be operative, depending upon the polymer from which they were made-one, (I) for the high molecular weight P(DL)LA, and the other, (II) for all PLGAs and the low molecular weight P(DL)LA. Microspheres of category I showed clear evidence of heterogeneous degradation, where the initially dense microsphere developed a hollow interior. Microspheres of category II plasticized on hydration due to reduction in the T_g of the polymer below the incubation temperature of 37°C. There was suppression of release of entrapped globular proteins from microspheres that underwent plasticization (category II), while slow and sustained release was seen from those that did not (category I). It is proposed that plasticization renders the matrix of category II microspheres non-porous, which prevents release by pore-diffusion. The mass loss profiles of PLGA were found to be different from those reported in the literature, in that the rates of mass loss after an initial lag time were not as rapid as has been reported. The experimental conditions used, namely the use, or otherwise, of agitation, is suggested as the reason for these differences and the need to draw a correlation between in vitro experimental conditions and in vivo behaviour is emphasized.