Nano-in-microparticles approach: Targeted gastric ulcer therapy using trans-resveratrol nanoparticles encapsulated in hyaluronic acid and alginate microparticles.

Gastric ulcers affect 4 million people worldwide and occur when the stomach's defenses are compromised, allowing harmful agents, such as nonsteroidal anti-inflammatory drugs and Helicobacter pylori, to damage the tissue. The naturally occurring polyphenol, trans-resveratrol (RESV), demonstrates promising potential for treating gastric diseases. However, its therapeutic application is limited by its photosensitivity and solubility. To overcome these challenges, RESV was encapsulated in a new nano-in-microparticle system comprised of chitosan nanoparticles incorporated into hyaluronic acid and alginate microparticles (RESV-MNP). RESV-MNP exhibited spherical morphology (~2 μm) and encapsulation efficiency of 79 %, releasing about 41 % of RESV within 24 h, showing a prolonged release profile compared to the free drug. Additionally, RESV-MNP interacted with porcine mucin in an acid environment. RESV-MNP showed no toxicity against AGS/MKN-74 cell lines in vitro and in acute toxicity tests using Galleria mellonella and hemolysis. RESV-MNP presented a minimum inhibitory and bactericidal concentration (MIC/MBC) of 3.9 μg/mL, eradicating H. pylori after 24 h. At 2×MIC, RESV-MNP completely eradicated H. pylori biofilm. In an in vitro infection assay, RESV-MNP reduced H. pylori load. The formulation effectively reduced the mortality rate of H. pylori-infected larvae in the G. mellonella model. Furthermore, RESV-MNP demonstrated gastroprotective effects, reducing the extent and severity of indomethacin-gastric lesions in rats.