Famotidine-loaded chitosan hybridized fibroin nanoparticles exhibit outstanding efficacy in ameliorating peptic ulcer.

Famotidine (FMD) is an H₂-receptor antagonist with limited oral bioavailability and a short plasma half-life (2.5-4 h). Silk fibroin-chitosan nanoparticles (FBN-CS-NPs) represent a novel nanocarrier approach for treating peptic ulcers, combining biocompatibility, mucoadhesiveness, and pH-sensitive release. These nanoparticles were developed by electrostatic interactions between fibroin and chitosan to improve FMD encapsulation and mucosal retention and potentiate its therapeutic efficacy. The optimized formulation demonstrated a particle size of 94.4 ± 3.6 nm, a zeta potential of +65.3 ± 4.6 mV, and 91.5 ± 5.4 % entrapment efficiency. The nanoparticles exhibited a sustained in vitro release over 24 h. FTIR, DSC, confirmed successful nanoparticle synthesis and drug incorporation, and TEM mean size 81.9 nm. In vivo studies on the gastric ulcer rat model revealed that FMD-FBN-CS-NPs significantly enhanced antioxidant defense (GSH increased by 436.6 %, MDA decreased by 74.19 %), and eNOS expression (466.38 %). It also significantly reduced H+/K+ ATPase (66.67 %) and cAMP (77.79 %) compared to the +ve-control group. Notably, even the plain FBN-CS-NPs exhibited considerable gastroprotective effects, supporting the healing potential of the fibroin-chitosan matrix. Histopathological analysis supported the gastroprotective impact of FMD-FBN-CS-NPs. These findings underscore the novelty and therapeutic promise of FBN-CS-NPs as a dual-function platform for drug delivery and mucosal healing in ulcer management.