Experimental and computational understanding of pulsatile release mechanism from biodegradable core-shell microparticles
Morteza Sarmadi, Christina Ta, Abigail M. VanLonkhuyzen, Dominique C. De Fiesta, Maria Kanelli, Ilin Sadeghi, Adam M. Behrens, Bailey Ingalls, Nandita Menon, John L. Daristotle, Julie Yu, Róbert Langer, Ana Jaklenec
Abstract
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.