pH-sensitivity and pH-dependent interior structural change of self-assembled hydrogel nanoparticles of pullulan...

pH-sensitive hydrogel nanoparticles that respond to the local acidic pH found in various diseased states such as tumors, ischemia and inflammation were prepared from pullulan acetate/oligo-sulfadimethoxine (PA/OSDM) conjugates. PA/OSDM nanoparticles prepared by dialysis at pH 9.5 had a spherical shape with a size range of 50-140 nm and low critical aggregation concentration (CAC) (<12 x 10(-3) mg/ml), dependent on the degree of substitution of OSDM (DS). With a decrease in dialysis pH (pHdia), the CAC gradually decreased due to the increase in the hydrophobic nature of OSDM. The nanoparticles prepared at pHdia 8.0 from the polymer with DS 1.0 aggregated in a pH range of 6.6-7.2 while the aggregation of nanoparticles prepared below pHdia 7.4 occurred in a broader pH range with a downshifted transition pH. These results indicate that the CAC and sharpness of the pH sensitivity of self-assembled hydrogel nanoparticles can be controlled by the pH of the dialysis buffer. In addition, the photophysical and photochemical characteristics of the nanoparticles were examined by a fluorescence probe technique. The micropolarity was monitored by pyrene and the microviscosity was measured by 1,6-diphenyl-1,3,5,-hexatriene (DPH) in the core of nanoparticles. Both properties dramatically changed as the pH decreased from 7.2 to 6.8, indicating that the interior restructuring of the hydrogel nanoparticles changed rapidly in this pH range. This is probably due to recruitment of hydrophobic group of deionized OSDM into the core. The pH sensitivity of the nanoparticles affected their drug release behavior. Doxorubicin (DOX) release from the PA/OSDM nanoparticles showed pH-dependent profiles around physiological pH and was significantly promoted at pH<6.8.