Experimental and computational understanding of pulsatile release mechanism from biodegradable core-shell microparticles

Next-generation therapeutics require advanced drug delivery platforms with precise control over morphology and release kinetics. A recently developed microfabrication technique enables fabrication of a new class of injectable microparticles with a hollow core-shell structure that displays pulsatile release kinetics, providing such capabilities. Here, we study this technology and the resulting core-shell microstructures. We demonstrated that pulsatile release is governed by a sudden increase in porosity of the polymeric matrix, leading to the formation of a porous path connecting the core to the environment. Moreover, the release kinetics within the range studied remained primarily independent of the particle geometry but highly dependent on its composition. A qualitative technique was developed to study the pattern of pH evolution in the particles. A computational model successfully modeled deformations, indicating sudden expansion of the particle before onset of release. Results of this study contribute to the understanding and design of advanced drug delivery systems.