Recently a number of hydrogel-based micro-and nanoscale drug carriers have been reported including top down fabricated, highly monodisperse nanoparticles of specific sizes and shapes. One critical question on such approaches is whether in vivo swelling of the nanoparticles could considerably alter their geometry to a point where the potential benefit of controlling size or shape could not be realized. Little has been reported on experimental characterization of the swelling behavior of

more »

... hydrogel structures, and current theoretical understanding is largely based on bulk hydrogel systems. Using atomic force microscopy (AFM) and environmental scanning electron microscopy (ESEM) capsules, we have characterized the swelling behavior of nano-imprinted hydrogel particles of different sizes and aspect ratios. Our results indicate a size-dependent swelling which can be attributed to the effect of substrate constraint of as-fabricated particles, when the particles are still attached to the imprinting substrate. Numerical simulations based on a recently developed field theory and a nonlinear finite element method were conducted to illustrate the constraint effect on swelling and drying behavior of substrate-supported hydrogel particles of specific geometries, and compared closely with experimental measurements. Further, we present a theoretical model that predicts the size-dependent swelling behavior for unconstrained sub-micron hydrogel particles due to the effect of surface tension. Both experimental and theoretical results suggest that hydrogel swelling does not significantly alter the shape and size of highly crosslinked nanoscale hydrogel particles used in the present study. † Electronic supplementary information (ESI) available: Additional scanning electron microscopy and atomic force microscopy results. Full derivation of surface tension effects. See