Original Development of Stimulus-Responsive Nanogel Drug Delivery Systems for Targeted Cancer Treatment Using Nigerian Plant-Derived Crosslinkers

Cancer mortality in Nigeria is disproportionately high relative to incidence because of late diagnosis and limited access to targeted therapy, and the development of targeted drug delivery systems using locally sustainable materials represents a critical translational research priority. Stimulus-responsive nanogels that release drugs selectively in response to the tumour microenvironment, characterised by reduced pH, elevated glutathione, and overexpressed enzymes, offer a compelling targeted delivery strategy. This study developed original stimulus-responsive nanogel systems using biocompatible polymers crosslinked with bifunctional crosslinking agents derived from Nigerian plant sources, specifically tannic acid from tannin-rich plant materials abundantly available in South West Nigeria and quercetin from onion skin and other agricultural by-products. Nanogels were prepared by free-radical emulsion polymerisation, inverse miniemulsion polymerisation, and physical crosslinking techniques. pH-responsive, glutathione-responsive, and dual-stimulus systems were fabricated and comprehensively characterised for size, morphology, surface charge, swelling behaviour, drug loading capacity, encapsulation efficiency, in vitro release kinetics, and cytocompatibility. Doxorubicin was used as a model anticancer drug. Dual pH- and glutathione-responsive nanogels showed 3.2-fold higher drug release at pH 5.0 and 10 mM glutathione compared to physiological conditions, demonstrating tumour microenvironment selectivity. In vitro cytotoxicity against MCF-7 breast cancer cells was enhanced 4.7-fold compared to free drug at equivalent doses. Selectivity over normal fibroblast cells was confirmed by differential cytotoxicity measurements. This work constitutes an original contribution to nanomedicine chemistry drawing on Nigerian plant resources and provides a foundation for preclinical evaluation of locally sourced, low-cost targeted cancer nanomedicine.

Keywords: nanogel drug delivery, stimulus-responsive, doxorubicin, targeted cancer therapy, Nigerian plant crosslinkers