Vonoprazan-loaded zinc oxide nanoparticles for the effective treatment of gastric ulcers: development, optimisation, in vitro and in vivo preclinical evaluation
摘要
Zinc oxide nanoparticles (ZnONPs) are a promising drug carrier for the treatment of various diseases due to their biocompatibility, nontoxicity, and controlled-release properties. The present study aimed to develop vonoprazan (VP)- loaded ZnONPs (VP-ZnONPs) for the treatment of gastric ulcers. The VP-ZnONPs were prepared by direct precipitation and optimized using the design expert software. The zinc acetate dihydrate, sodium hydroxide, and stirring speed were selected as independent variables, whereas particle size, entrapment efficiency, and polydispersity index (PDI) were selected as responses. The optimized VP-ZnONPs (VP-ZnONPsopt) showed a particle size of 156.3 ± 3.4 nm, 0.371 ± 0.004 of PDI, 81.74 ± 0.50% of EE%, and 21.1 mV (negative) zeta potential. FTIR spectra of VP-ZnONPsopt showed no interaction between the drug and the formulation ingredient. Differential scanning calorimetry study showed the drug was encapsulated into the NPs matrix. The VP-ZnONPsopt exhibited a sustained VP release profile over an extended period (95.5% at 24 h). VP-ZnONPsopt exhibited significantly higher ex-vivo intestinal permeation than pure VP-dispersion. The VP-ZnONPsopt exhibited significantly higher (p < 0.05) anti-ulcer activity (62.15%) than pure VP-dispersion (37.08%). Based on the findings, strategies to enhance VP delivery include drug-induced gastroprotection, improved gastric localization, and sustained release.
Graphical abstract