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This work represents a detailed investigation into the phase and morphological behavior of synergistic dual-stimuli-responsive poly(N-isopropylacrylamide) nanogels, a material that is of considerable interest as a matrix for in situ forming implants. Nanogels were synthesized with four different diameters (65, 160, 310, and 450 nm) as monodispersed particles. These different samples were then prepared and characterized as both dilute (0.1 wt %) and concentrated dispersions (2–22 wt %). In the dilute form, all of the nanogels had the same response to the triggers of the physiological temperature and ionic strength. In water, the nanogels would deswell when heated above 32 °C, while they would aggregate if heated above this temperature at the physiological ionic strength. In the concentrated form, the nanogels exhibited a wide range of morphological changes, with liquid, swollen gel, shrunken gel, and aggregate structures all possible. The occurrence of these structures was dependent on many factors such as the temperature, ionic strength of the solvent, size and ζ-potential of the nanogel, and dispersion concentration. We explored these factors in detail with techniques such as visual studies, rheology, effective volume fraction, and shape factor measurement. The different-sized nanogels displayed differing phase and morphological behavior, but generally higher concentrations of the nanogels (>7 wt %) yielded gels in water with the transitions depending on the temperature. The smallest nanogel (65 nm diameter) exhibited the most unique behavior; it did not form a swollen gel at any concentration tested. Shape factor measurement for the nanogel samples showed that two of the larger three samples (160 and 310 nm) had core–shell structures with denser core cross-linking, while the smallest nanogel sample displayed a homogeneous cross-linked structure. We hypothesize that the smallest nanogels are able to undergo more extensive interpenetration compared to the larger nanogels, which meant that the smallest nanogel was not able to form a swollen gel. In the presence of salt at 12 wt %, all of the nanogels formed aggregates when heated above 35 °C due to the screening of the electrostatic stabilization by the salt. This work revealed unique behavior of the smallest nanogel with a homogeneous cross-linked structure; its phase and morphological behavior were unlike a particle dispersion, rather these were more similar to those of a branched polymer solution. In total, these findings can be used to provide information about the design of poly(N-isopropylacrylamide) nanogel dispersions for different applications where highly specific spatiotemporal control of morphology is required, for example, in the formation of in situ forming implants or for pore blocking behavior.

Dynamic nuclear polarization (DNP) solid-state NMR was used to obtain natural abundance (13)C and (15)N CP MAS NMR spectra of microporous organic polymers with excellent signal-to-noise ratio, allowing for unprecedented details in the molecular structure to be determined for these complex polymer networks. Sensitivity enhancements larger than 10 were obtained with bis-nitroxide radical at 14.1 T and low temperature (∼105 K). This DNP MAS NMR approach allows efficient, high-throughput characterization of libraries of porous polymers prepared by combinatorial chemistry methods.

Polymers and surfactants are commonly used as excipients in oral formulations and are generally considered to be inert. However, relatively few studies have assessed their interaction with enzymes involved in the absorption, distribution, metabolism, and elimination of drugs. We have investigated the impact of twenty-three commonly used excipients (ten polymers and thirteen surfactants) on seven cytochrome P450 (CYP450) isoforms using baculosome-derived CYP450 enzymes across a range of concentrations. Time-course fluorescent readings were then taken to generate IC50 (inhibition) or EC50 (activation) values for excipient effects on CYP450 activity. All excipients had an observable effect activity of at least one CYP450 isoform with the majority of excipients altering substrate metabolism of at least 57% of CYP450s studied. In addition, most excipients were capable of inhibiting and increasing activity of several different CYP450 isoforms. Although the majority of these effects required concentrations outsi...