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

The in vitro degradation of microspheres of polymers of lactic and glycolic acids were investigated by monitoring the mass loss from the device, the m olecular weight of the polymer and the morphological changes of the particl es with time. Two different sequences of morphological changes were found t o 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 PLG As and the low molecular weight P( DL) LA. Microspheres of category I showe d clear evidence of heterogeneous degradation, where the initially dense mi crosphere developed a hollow interior. Microspheres of category II plastici zed on hydration due to reduction in the Tg of the polymer below the incuba tion temperature of 37 degreesC. There was suppression of release of entrap ped globular proteins from microspheres that underwent plasticization (cate gory II), while slow and sustained release was seen from those that did not (category I). It is proposed that plasticization renders the matrix of cat egory II microspheres non-porous, which prevents release by pore-diffusion. The mass loss profiles of PLGA were found to be different from those repor ted 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 us ed, 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 e xperimental conditions and in vivo behaviour is emphasized.