Rutin loaded nanosponges for treatment of peptic ulcer: in silico, pharmacodynamic and pharmacokinetic studies.

Peptic ulcer disease (PUD) is a multifactorial condition influenced by oxidative stress, Helicobacter pylori infection and excessive gastric acid secretion. Rutin (RTN), a plant-derived flavonoid with antioxidant, anti-inflammatory and proton pump inhibition properties, offers therapeutic promise but suffers from poor aqueous solubility and low bioavailability. To overcome these limitations, RTN-loaded β-cyclodextrin-based nanosponges (RTN-NS₄) were developed and extensively characterized. Phase solubility studies revealed AL type of curve. DSC and PXRD indicated enhanced amorphization while FTIR confirmed successful drug encapsulation. SEM imaging revealed flaky, nanoscale morphology. RTN-NS₄ exhibited a 25.4-fold increase in saturation solubility compared to RTN. Antioxidant potential, assessed by DPPH assay, showed significantly higher antioxidant activity for RTN-NS₄ of 87.91% at 500 μg/ml, indicating enhanced ROS-scavenging ability. Molecular docking studies further confirmed RTN's strong binding affinity towards H+/K+-ATPase (glide energy of -62.822 kcal/mol) showing enhanced binding affinity and complex stability. In comparison, vonoprazon showed glide energy of -58.450 kcal/mol. These studies also confirmed that RTN has greater binding with NS (glide energy:-37.924 kcal/mol) than β-CD (glide energy:-33.034 kcal/mol). RTN-NS₄ achieved 42 ± 7.23% ulcer inhibition in ethanol-induced gastric ulcers in Wistar rats, surpassing RTN (22.17 ± 6.53%) but 18% lower than omeprazole (60.16 ± 8.23%). Histological studies confirmed moderate mucosal protection and reduced inflammation in RTN-NS₄-treated rats. These results underscore RTN-NS₄ as promising nanophyto-therapeutic system offering synergistic antioxidant, anti-inflammatory and PPI activity effects for effective ulcer management without the concomitant side effects of PPIs.