pH-Responsive, Reactive Oxygen Species Scavenging and Highly Swellable Nanogel for Colon-Targeted Oral Drug Delivery

In the realm of colon-based drug delivery, developing a pH-responsive nanocarrier that exhibits significant intrinsic reactive oxygen species (ROS) scavenging activity holds great promise. To address this, a nanogel (NG) is synthesized using itaconic acid (IAc) and acrylamide (AAm) monomers in a molar ratio of 1:4 via free radical polymerization. The spherical NG of size 190 +/- 15 nm is confirmed by using field emission scanning electron microscopy (FESEM). Dynamic light scattering (DLS) characterization reveals a hydrodynamic diameter and zeta potential of 271 +/- 23 nm and -6.9 +/- 2.3 mV, respectively. FTIR, XPS, and NMR analyses confirm the presence of multiple functionalities on the NG. Significant improvement in swelling (10 times) at colonic pH (pH 7.4) in contrast to gastric pH (pH 1.2) ensures the pH-responsive behavior of a NG along with five times higher ROS scavenging activity compared to control. As a model drug, doxorubicin (DOX) is employed to investigate release properties and cellular uptake. The NG exhibited drug loading capacity and efficiency of 26 +/- 1.2% and 90 +/- 1.3%, respectively, with a three times higher DOX release at pH 7.4 than at pH 1.2. Rheology data reveal the superior structural integrity of the doxorubicin loaded nanogel (DNG) compared to the NG. The biocompatibility of the NG is confirmed through MTT, the hemolysis assay, and cell uptake assays on HCT-116 colon cancer cells. The cellular uptake studies have indicated NG-mediated drug release in the colon microenvironment with subsequent passive diffusion of DOX into cells. These findings underscore the capability of the synthesized NG as a vehicle for oral drug delivery to the colon.