Visual evidence of acidic environment within degrading poly(lactic-co- glycolic acid) (PLGA) microspheres

Purpose. In the past decade, biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular, poly(lactic-co-glycolic acid) (PLGA) microspheres have been extensively studied for controlled-release drug delivery. However, degradation of the polymer generates acidic monomers, and acidification of the inner polymer environment is a central issue in the development of these devices for drug delivery. Methods. To quantitatively determine the intrapolymer acidity, we entrapped pH-sensitive fluorescent dyes (conjugated to 10,000 Da dextrans) within the microspheres and imaged them with confocal fluorescence microscopy. The technique allows visualization of the spatial and temporal distribution of pH within the degrading microspheres (1). Results. Our experiments show the formation of a very acidic environment within the particles with the minimum pH as low as 1.5. Conclusions. The images show a pH gradient, with the most acidic environment at the center of the spheres and higher pH near the edges, which is characteristic of diffusion-controlled release of the acidic degradation products.