Development of pH-responsive chitosan/heparin nanoparticles for stomach-specific anti- Helicobacter pylori therapy

• Published in: Biomaterials 2009-07, Vol.30 (19), p.3332-3342
• Main Authors: Lin, Yu-Hsin, Chang, Chiung-Hung, Wu, Yu-Shiun, Hsu, Yuan-Man, Chiou, Shu-Fen, Chen, Yi-Jen
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Biocompatible Materials - chemistry; Biocompatible Materials - therapeutic use; Cells, Cultured; Chitosan; Chitosan - chemistry; Chitosan - therapeutic use; Coculture Techniques; Dentistry; Fluorescent Dyes - metabolism; Gastric Mucosa - cytology; Gastric Mucosa - microbiology; Helicobacter Infections - drug therapy; Helicobacter pylori; Helicobacter pylori - physiology; Heparin; Heparin - chemistry; Heparin - therapeutic use; Humans; Hydrogen-Ion Concentration; Intercellular spaces; Male; Materials Testing; Mice; Mice, Inbred BALB C; Molecular Structure; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Peptic ulcers
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.02.036

Abstract The microorganism now known as Helicobacter pylori is considered to be an important factor in the etiology of peptic ulcers. It can secrete urease enzyme and buffer gastric acids to survive in the stomach. H. pylori can colonize the gastric mucosa and preferentially adheres near the cell–cell junctions of the gastric mucous cells. In this study, pH-responsive nanoparticles were produced instantaneously upon the addition of heparin solution to a chitosan solution with magnetic stirring at room temperature. The nanoparticles appeared to have a particle size of 130–300 nm, with a positive surface charge, and were stable at pH 1.2–2.5, allowing them to protect an incorporated drug from destructive gastric acids. We also demonstrated that the prepared nanoparticles can adhere to and infiltrate cell–cell junctions and interact locally with H. pylori infection sites in intercellular spaces.