Revolutionizing colon cancer therapy by site-specific 5-fluorouracil delivery with novel stimuli-responsive mucoadhesive hydrogel: Optimization via response surface methodology

5-fluorouracil (FU) is the key option of systemic therapy for advanced metastatic colon cancer but has a cytotoxic impact on normal cells after intravenous administration therefore the primary goal of this research was to fabricate a unique oral site-specific mucoadhesive delivery technique for FU to reach the colon and improving the targeting effectiveness of FU to colon. In the present research, we investigate the novel utilization of developed carboxymethyl cellulose/polyvinylpyrrolidone-grafted-poly(acrylic acid) based hydrogel as a potential carrier for FU administration. The utilization of such novel hydrogels as potential mucoadhesive and swelling behaviour candidates, carriers of FU for colon cancer, as well as the in-vitro evaluations of FU-release, Fourier transform infrared spectroscopy (FTIR), 13C Nuclear magnetic spectroscopy (13C NMR), X-ray diffraction (XRD), thermal analysis, average molecular weight between crosslinks (Mc), cross-link density, in addition to cytotoxicity analysis, hemocompatibility evaluation and acute oral toxicity analysis, were carried out. Notably, over the initial 36 h of dissolution, FU % cumulative release from CMC/PVP-g-poly (AA) hydrogel ranges from 2.62 % to 6.60 % at 1.2 pH, 7.23 %–11.35 % at 6.8 pH, and 85.48 %–99.63 % at 7.4 pH, respectively. Its thermal stability has been demonstrated by TGA and DSC. The FTIR, 13C NMR and XRD have verified the molecular-level entrapment of FU inside the designed hydrogel. Scanning Electron Microscopy (SEM) results showed that the produced hydrogel had an irregular along with porous surface. The degree of a hydrogel's swelling and crosslink density were found to be negatively correlated with each other, whereas Mc was directly linked with the swelling of accomplished hydrogel. The developed hydrogel with the highest carboxymethyl cellulose (CMC) content demonstrated 147 min of mucoadhesion with colonic mucosal lining. Cytotoxicity analysis, hemocompatibility evaluation and acute oral toxicity testing confirmed the biocompatibility of the fabricated hydrogel and indicated their potential for safe as well as site-specific sustained FU transport as well as being used as a valuable asset of therapeutic agents for colon cancer treatment. [Display omitted]