Switchable On-Demand Release of a Nanocarrier from a Segmented Reservoir Type Intravaginal Ring Filled with a pH-Responsive Supramolecular Polyurethane Hydrogel.

To achieve a pH-responsive switchable on-demand release of nanoparticles (NPs) from intravaginal rings (IVR), a new pH-sensitive polyurethane (PU) bearing dimethylolpropionic acid (PEG-DMPA-HDI-PG) was synthesized to encapsulate NPs as a physically cross-linked hydrogel within a segmented reservoir-IVR. A new PEGylated polyaspartic acid-based copolymer conjugated with the fluorescent dye Orange II (PASP-PEG-Ph-Orange) was synthesized to self-assemble in aqueous solution into NPs (251-283 nm) for the release study. Chemical structures of the PEG-DMPA-HDI-PG and PASP-PEG-Ph-Orange were confirmed by attenuated total reflectance Fourier transform infrared (ATR-FTIR) and 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy. PASP-PEG-Ph-Orange NPs showed the highest fluorescent emission at 570 nm for tracking, and PEG-DMPA-HDI-PG became a pH-responsive supramolecular hydrogel in distilled water at 20 wt %. PASP-PEG-Ph-Orange NPs were blended with the PEG-DMPA-HDI-PG hydrogel to form an inclusion complex and then filled into segmented reservoir-IVRs containing two 1/32 in. diameter holes. The segmented IVR filled with the NP encapsulated hydrogel showed continuous release of the NPs at pH 7.0 but a close-to-zero release at pH 4.2 for 12 h and, moreover, demonstrated a pH-responsive switchable on-demand NPs release. The PASP-PEG-Ph-Orange and PEG-DMPA-HDI-PG showed no and low cytotoxicity toward the human vaginal epithelial cell line VK2/E6E7, respectively. Overall, the segmented IVR filled with PEG-DMPA-HDI-PG hydrogel demonstrated its potential use for the switchable on-demand intravaginal release of nanocarriers.