Monitoring the Erosion of Hydrolytically-Degradable Nanogels via Multiangle Light Scattering Coupled to Asymmetrical Flow Field-Flow Fractionation

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We describe the synthesis and characterization of degradable nanogels that display bulk erosion under physiologic conditions (pH = 7.4, 37 degrees C. Erodible poly(N-isopropylmethacrylamide) nanogels were synthesized by copolymerization with N,O-(dimethacryloyl) hydroxylamine, a cross-linker previously used in the preparation of nontoxic and biodegradable bulk hydrogels. To monitor particle degradation, we employed multiangle light scattering and differential refractometry detection following asymmetrical flow field-flow fractionation. This approach allowed the detection of changes in nanogel molar mass and topology as it function of both temperature and pH. Particle erosion was evident from both an increase in nanogel swelling and a decrease in scattering intensity as a function of time. Following these analyses, the samples were recovered for subsequent characterization by direct particle tracking, which yields hydrodynamic size measurements and enables number density determination. Additionally, we confirmed the conservation of nanogel stimuli-responsivity through turbidity measurements. Thus, we have demonstrated the synthesis of degradable nanogels that erode tinder conditions and on time scales that are relevant for many drug delivery applications. The combined separation and light scattering detection method is demonstrated to be it versatile means to monitor erosion and should also find applicability in the characterization of other degradable particle constructs.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Analytical Chemistry, volume 82, issue 2, 2010 following peer review. The definitive publisher-authenticated version is available online at DOI: 10.1021/ac901725m.


American Chemical Society