Development of famotidine-loaded lecithin-chitosan nanoparticles for prolonged and efficient anti-gastric ulcer activity

Abstract

Lecithin-chitosan nanoparticles (LCNPs) represent an appealing nanocarrier for the oral delivery of hydrophobic drugs. Negatively charged lecithin and positively charged chitosan were permitted to interact to create LCNPs. Their distinctive features enable drugs to be encapsulated into the lipophilic lecithin core while improving their retention in gastric mucosa by the chitosan coat. Famotidine (FMD), a hydrophobic H2-receptor antagonist drug with a short half-life (2.5–4 h), was loaded into LCNPs to enhance its therapeutic efficacy in gastric ulcers through achieving good mucoadhesion and subsequent absorption. The optimal formula with a lecithin to chitosan ratio of 10:1 was selected and exhibited a particle size of 178.5 ± 9.5 nm, a zeta potential of 43.7 ± 2 mV, and an entrapment efficiency of 75.81 ± 2.5 %. It displayed a prolonged in vitro release profile (75.72 % over 24 h) and considerable mucoadhesive properties. FMD-LCNPs were also characterized by differential scanning calorimetry, Fourier transform-infrared (FTIR) spectroscopy, transmission electron microscopy, and stability studies. The in vivo study was performed on ethanol-induced gastric ulcer in a rat model, and the anti-gastric ulcer effects of FMD-free, FMD-marketed product, and FMD-LCNPs were determined by assessing the ulcer severity, antioxidant biomarkers, eNOS levels in addition to histopathological examination. FMD-LCNPs administration resulted in a percentage of protection from gastric severity of 96.25 % and an exceptional ameliorative effect on oxidative stress biomarkers (GSH; 162.36 % increase and MDA; 71.91 % decrease) as compared to other FMD forms. Additionally, FMD-LCNPs showed the strongest eNOS level improvement (130.34 %), which indicated the best healing impact and was confirmed by restoring the gastric mucosa to normal architecture.