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Microscopy and tunable resistive pulse sensing characterization of the swelling of pH-responsive, polymeric expansile nanoparticles

Colby, Aaron H; Colson, Yolonda L; Grinstaff, Mark W.
Nanoscale, 2013 - 5 (8): 3496-3504

Polymeric expansile nanoparticles (eNPs) that respond to a mildly acidic environment by swelling with water and expanding 2-10x in diameter represent a new responsive drug delivery system. Here, we use a variety of techniques to characterize the pH- and time-dependence of eNP swelling as this is a key property responsible for the observed in vitro and in vivoperformance of eNPs. Results demonstrate a significant change in eNP volume (>350x) at pH 5.0 as seen using: scanning electron microscopy (SEM), conventional transmission electron microscopy (TEM), freeze-fracture transmission electron microscopy (ff-TEM), fluorescence microscopy, and a new nanopore based characterization technology, the qNano, which measures both individual particle size as well as overall particle concentration in situ using tunable resistive pulse sensing. eNP swelling occurs in a continuous and yet heterogeneous manner over several days and is pH dependent.

Keywords: Acidic environment; Conventional transmission electron microscopies; Drug delivery system; Freeze-fracture transmission electron microscopies; Individual particles; Particle concentrations; Resistive pulse sensing; Time dependence

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