Peptic ulcer disease (PUD) is a multifactorial disorder driven by oxidative stress, Helicobacter pylori infection and excessive gastric acid secretion. The plant flavonoid rutin (RTN) exhibits antioxidant and anti-inflammatory properties and has been reported to interfere with proton pump activity, but its clinical utility is limited by poor aqueous solubility and low bioavailability. To address these limitations, the study developed RTN-loaded β-cyclodextrin-based nanosponges (RTN-NS4) as a nanocarrier intended to improve drug solubility, stability and pharmacological effect for ulcer management.
RTN-NS4 were prepared using β-cyclodextrin-based nanosponge technology and characterized by multiple physicochemical methods. Phase solubility analysis produced an AL-type curve, consistent with enhanced solubilization behavior in the presence of the carrier. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) showed changes indicating increased amorphization of RTN when incorporated into the nanosponge matrix. Fourier-transform infrared spectroscopy (FTIR) provided evidence of successful encapsulation of RTN within the nanosponge system. Scanning electron microscopy (SEM) revealed a flaky morphology at nanoscale dimensions.
Encapsulation in the nanosponge markedly improved the aqueous solubility of RTN: RTN-NS4 demonstrated a 25.4-fold increase in saturation solubility compared with free RTN. Antioxidant capacity was assessed by the DPPH radical scavenging assay; RTN-NS4 exhibited enhanced antioxidant activity, reaching 87.91% scavenging at 500 μg/ml. These results indicate that the nanosponge formulation improved both physicochemical solubility and in vitro antioxidant potential relative to the unformulated flavonoid.
Molecular docking simulations evaluated RTN interactions with therapeutic targets and with carrier components. RTN displayed a strong predicted binding affinity to the gastric proton pump H+/K+-ATPase, with a glide energy of -62.822 kcal/mol, indicating favorable complex formation and stability in silico. For comparison, vonoprazan showed a glide energy of -58.450 kcal/mol in the same docking framework. Docking also compared RTN affinity for the nanosponge construct versus β-cyclodextrin alone: RTN had a glide energy of -37.924 kcal/mol with the nanosponge (NS) model and -33.034 kcal/mol with β‑CD, suggesting stronger interaction with the nanosponge architecture than with β‑cyclodextrin alone.
Pharmacodynamic testing employed an ethanol-induced gastric ulcer model in Wistar rats. RTN-NS4 achieved 42 ± 7.23% ulcer inhibition in this preclinical model. Free RTN produced 22.17 ± 6.53% ulcer inhibition under the same conditions, while omeprazole produced 60.16 ± 8.23% ulcer inhibition. Thus, RTN-NS4 improved anti-ulcer efficacy compared with unformulated rutin but did not reach the efficacy observed with omeprazole in this acute ethanol model. The abstract does not report group sizes, dosing regimens, timing, or detailed statistical analyses; those methodological details are not available in the provided source.
Histological evaluation of gastric tissue from treated animals showed that RTN-NS4 provided moderate mucosal protection and reduced inflammatory changes relative to controls. These microscopic findings are consistent with the observed reduction in macroscopic ulceration and the increased antioxidant potential demonstrated in vitro. The abstract does not provide microphotographs, scoring methodology or quantification beyond the descriptive statements summarized here.
The study concludes that RTN-NS4 is a promising nanophyto-therapeutic platform for peptic ulcer management, combining enhanced solubility, improved antioxidant activity and predicted proton pump interaction. In silico docking suggested strong RTN binding to H+/K+-ATPase, and preclinical data showed superior ulcer inhibition and histological protection versus free RTN, though less than omeprazole in the ethanol model. The authors propose that RTN-NS4 may offer synergistic antioxidant, anti-inflammatory and proton-pump inhibitory effects without the side-effect profile associated with chronic PPI use. The abstract does not include comprehensive experimental details (full methods, sample sizes, statistical tests, long-term safety or pharmacokinetic parameters beyond those summarized), so readers should consult the full article for complete methodology and data.