Abstract
Helicobacter pylori (H. pylori) infection affects about half the world population, and if left untreated, can cause painful sores in the stomach lining and intestinal bleeding, leading to peptic ulcer disease (PUD) and stomach cancer. Treatment of H. pylori infection is always a challenge to the treating doctor because of the treatment inefficiency resulting from the poor bioavailability of the drug at the inner layers of the gastric mucosa, where the bacteria reside. This also results in the development of antibiotic resistance. In this work, we developed a mucoadhesive gastroretentive drug delivery system (M-GRDDS) for the effective delivery of antibiotics and piperine to the gastric mucosa. The GRDDS system was formulated by using the ion-gelation method and was evaluated for its entrapment efficiency, particle size, swelling behavior, drug release, mucoadhesion property, and H. pylori eradication efficacy. The efficacy of the drug-loaded mucoadhesive GRDDS formulation was compared with that of the free drug. Results showed that the percentage entrapment efficiency was more than 80% for all the drugs. M-GRDDS beads showed controlled release at pH 1.2 and 7.4. The optimized mucoadhesive beads showed good in vitro mucoadhesion in X-ray photography, with a mean gastric residence time of more than 8 h in rabbits. Tissue distribution study in rats revealed local delivery of the drugs to the gastric mucosa from the M-GRDDS beads. The in vivo efficacy study performed on Sprague-Dawley rats showed that the colony-forming units in the group treated with the novel GRDDS formulation were fewer than those in the group treated with the free drugs. Biochemical tests, gene expression studies, and histopathology studies corroborated the enhanced efficacy of the M-GRDDS formulation in eradicating the infection and curing peptic ulcers. The results conclude that the developed M-GRDDS formulation holds significant potential for improving local bioavailability, contributing to the more effective eradication of H. pylori-based gastric ulcers.