Reduction-Sensitive Poly(ethylenimine) Nanogel Bearing Dithiodipropionic Acid

Reduction-sensitive nanogel was developed by including dithiodipropionic acid (DTPA) in tripolyphosphoric acid (TPPA) cross-linked poly(ethylenimine) (PEI) nanogel. According to the light scattering measurement, DTPA (a disulfide compound) seemed to cross-link PEI chains in a cooperative manner with TPPA (a multi-valent anion). Nanogels composed of TPPA, PEI, and DTPA exhibited negative zeta potential and the absolute value increased with the amount of TPPA and DTPA. TPPA and DTPA were found to be contained in the nanogel, evidenced by Fourier transform (FT)-IR spectroscopy and Raman spectroscopy, respectively. 1H-NMR spectroscopy also revealed DTPA was contained in the nanogel. The DTPA content in the nanogel was determined colorimetrically to be 7.14 and 9.4%, depending on the DTPA content in the raw mixture for the preparation of nanogel. On the transmission electron microscopy (TEM) micrographs of the negatively stained nanogel, the diameter was about 20–30 nm. The specific loading of carboxylic fluorescein (CF) in the nanogel was around 1.8%, determined by fluorometric analysis, and it was not affected by the DTPA content. The maximum release degree of CF loaded in nanogel containing no DTPA was less than 10% and it was almost the same regardless of dithiothreitol (DTT) concentration. Whereas, the release of the dye loaded in nanogel containing DTPA was markedly promoted by DTT, possibly because the disulfide bond can be broken by DTT and the diffusivity of the dye through the nanogel matrix can increase.