A repurposing Dapagliflozin via polymeric nanogels for colorectal cancer therapy

Dapagliflozin (DAPA), a selective SGLT2 inhibitor approved for type 2 diabetes, shows emerging potential for repurposing in oncology due to its anti-inflammatory and antiproliferative properties. However, its poor solubility and rapid systemic clearance limit its therapeutic utility in cancer treatment. Here, we report the development of an oral novel gravity-induced nano hydrogel mass system encapsulating DAPA using sodium alginate (SA) and polyvinyl alcohol (PVA) nanoparticles (DAPA-PVA-SA-NPs). The formulation exhibited enhanced solubility (1.8-fold increase), high encapsulation efficiency (88.37%), and sustained release in simulated gastrointestinal conditions. In vitro studies demonstrated improved cytotoxicity against HCT-116 colorectal cancer cells and significant downregulation of oncogenic and inflammatory markers (KRAS, IL-6, TGF-β, TNF-α). In vivo pharmacokinetic evaluation in rats showed delayed Tmax, extended half-life, and a 7% increase in AUC, indicating prolonged systemic exposure with modest AUC improvement. This delivery platform improves oral exposure in rats, shows in vitro activity in HCT-116 cells and supporting further exploratory evaluation for repurposing DAPA in colorectal cancer, pending confirmation in additional models.