Enhancing the Therapeutic Profile of Dapagliflozin: Chitosan Nanoparticle Encapsulation for Intestinal Applications.

Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor primarily used to treat type 2 diabetes by lowering blood glucose levels. In addition to its antidiabetic action, it has demonstrated cardioprotective and renoprotective effects, along with antioxidant, anti-inflammatory, and anticancer activities. Encapsulation of dapagliflozin in nanocarriers represents an innovative strategy to improve existing therapies and develop targeted treatments. Such formulations can enhance solubility and stability, improve epithelial permeability and bioavailability, and reduce potential side effects. This study investigates the cellular and molecular effects of dapagliflozin encapsulated in chitosan nanoparticles, focusing on colon (Caco-2) cells. The findings showed that free dapagliflozin significantly reduced cell viability, whereas the encapsulated form preserved high cell viability. In addition, the encapsulated drug effectively reduced reactive oxygen species levels, maintaining its antioxidant activity. Free dapagliflozin did not increase the expression of Nrf2, NFκB, or HO-1 signaling pathways. In contrast, encapsulation in chitosan nanoparticles resulted in increased expression of all three pathways, indicating potential regulatory involvement in these signaling mechanisms.