The Impact of the pH on the Concentration of the Released Ogremorphin-Mimic Dye from Double-Network Hydrogels for Glioblastoma Localized Treatment

Glioblastoma (GBM), a highly aggressive brain cancer, poses significant treatment challenges due to its complex microenvironment and low therapeutic efficacy of current approaches. Localized drug delivery systems hold promise for improving therapeutic outcomes. This study investigated the release of an Ogremorphin (OGM)-mimic dye from a double-network hydrogel (DNH) designed for GBM therapy, hypothesizing that the hydrogel would have a steady release of the mimic drug at a lower pH. A polyacrylamide alginate DNH was synthesized, and its swelling behavior, drug-loading efficiency, and release dynamics were evaluated. The hydrogel’s swelling degree was calculated after 72 hours of immersion in distilled water. Drug loading efficiency was determined by UV-Vis spectroscopy, measuring the residual concentration of a fluorescein solution. Dye release was assessed under various pH conditions from 4-8, simulating the tumor microenvironment (TME), with cumulative release profiles analyzed over 228 hours. The hydrogel exhibited a swelling degree of 135.8% and a drug loading efficiency of 87.4%. Drug release was pH-dependent, with minimal release at acidic pH (4 and 5) due to a compact polymer network and an increased release at alkaline pH 8, driven by network swelling. Statistical results from the one-way ANOVA test showed that F(4, 85) = 17.72, p < .001. A post-hoc Tukey test showed a significant difference between the different pH levels. Optimized formulations at pH 4- 6 could minimize burst release, sustain therapeutic levels, and improve patient outcomes. These findings demonstrated the hydrogel’s pH-responsive properties made it a strong candidate for GBM therapy.