Sequential loading of inclusion complex/nanoparticles improves the gastric retention of Vladimiriae Radix essential oil to promote the protection of acute gastric mucosal injury

The essential oil from Vladimiriae Radix (VEO) is a medicinal natural product with anti-ulcer activity. A novel gastroretentive drug delivery system was developed by preparing the hydroxypropyl-13-cyclodextrin (HP-13-CD) inclusion complex incorporated into chitosan nanoparticles (V-CD/NPs), to improve the bioavailability of VEO and its protective effect on gastric mucosa. The optimum preparation process of V-CD/NPs was obtained by Plackett-Burman and Box-Behnken response surface methodology. The resulting V-CD/NPs gained a suitable positive potential and small particle size, and showed stability in simulated gastric fluid, whose morphology and in vitro drug release profiles had a pH-sensitivity. Besides, V-CD/NPs was proved to strongly bind with mucin, and in vivo imaging revealed that it could be retained in the stomach for more than 8 h. The results of drug concentration in gastric tissues showed that the sequential loading of inclusion complex/nanoparticles promoted the local absorption of VEO in gastric tissues, which was favorable to reach the effective therapeutic concentration in the lesioned mucosa area. In comparison to VEO and V-CD, the callback effect of V-CD/NPs on 1L-113, 1L-6, TNF-a, NF-kappa B, MDA and SOD was comparable to cimetidine, and V-CD/NPs outperformed in gastric mucosal protection. Therefore, the gastroretentive drug delivery system developed in our study effectively enhanced the anti-ulcer activity of VEO, which could be a promising strategy for the prevention and treatment of the acute gastric mucosal injury.

Automated summary

A novel gastroretentive drug delivery system was successfully developed in this study, which enhanced the bioavailability and protective effect of VEO by combining inclusion complex and nanoparticles, potentially promising for the prevention and treatment of acute gastric mucosal injury.