Singh, H.JagadeeshBabu, J.Mohan Balakrishnan, R.2026-02-032025Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2025, 724, , pp. -9277757https://doi.org/10.1016/j.colsurfa.2025.137390https://idr.nitk.ac.in/handle/123456789/19991In this study, a novel pH-responsive hydrogel was developed by crosslinking amidated pectin(AmPec) with oxidised gum Arabic(GAA) by hydrogen and hemiacetal bonding without the need for toxic crosslinkers for oral delivery of doxorubicin to treat colon cancer. FTIR and NMR confirmed the amidation of pectin and oxidation of Gum Arabic. FTIR confirmed the formation of hydrogen and hemiacetal bonds in the hydrogel. X-ray diffraction(XRD) spectra showed the amorphous characteristic of AmPec-GAA hydrogels compared to their polymer precursors, confirming the formation of a crosslinked hydrogel. AmPec-GAA15 hydrogel swelled around 655 %±39.90 at pH 7.4 compared to 181 %±7.94 swelling at pH 1.2 after 72 h. The release of doxorubicin also followed the same trend, with only 4.48 % ±0.89 doxorubicin release at pH 1.2, while the drug release increased to 68.10 %±3.73 at pH 7.4 after 48 h. SEM micrographs revealed the macroporous and interconnected hydrogel structure with fewer pores in the hydrogel swelled in pH 1.2 compared with pH 7.4, where more visible pores were observed, indicating the pH-sensitive behaviour of the hydrogel. Hydrogel possessed excellent thermal and mechanical stability as revealed by TGA and rheology study, which can also be explored for tissue engineering applications. MTT assay on L929 cells showed cell viability above 95.1 %±,0.0074, demonstrating hydrogels' non-toxic and biocompatible behaviour. Meanwhile, Dox-loaded hydrogel induced higher cytotoxicity against HT-29 cells than free Dox in a dose-dependent manner. Therefore, the developed hydrogel can be used as an effective oral carrier to deliver doxorubicin to colon cancer while hindering its release in the stomach and thus preventing associated toxicity. © 2025 Elsevier B.V.Cell signalingCrosslinkingCytotoxicityFiber bondingMetabolic engineeringpH sensorsTargeted drug deliveryTissue homeostasisColon cancerCrosslinkerDoxorubicinFTIRGum arabicHemiacetalsOral drug deliveryPectinpH-responsive hydrogelspH-sensitive hydrogelControlled drug deliveryaldehydebiopolymerdoxorubicingum arabichydrogelhydrogenhydroxyl grouppectinpolymeramidationammonolysisArticleattenuated total reflectance Fourier transform infrared spectroscopybiodegradabilitycell viabilitycolon cancercontrolled studycross linkingcytotoxicitydrug releaseesterificationflow cytometryflow kineticsFourier transform infrared spectroscopygelationHT-29 cell linehumanhuman cellin vitro studyMTT assayNCTC clone 929 cell linenuclear magnetic resonanceoxidationpHscanning electron microscopysustained drug releasethermogravimetrytissue engineeringX ray diffraction