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 A_L 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.