Positively Charged Gelatin Microspheres as Gastric Mucoadhesive Drug Delivery System for Eradication of H. pylori

• Published in: Drug delivery 2000, Vol.7 (4), p.237-243
• Main Author: Jian Wang, Yoshihiko Tauchi, Yoshiharu Deguchi, Kazuhiro Morimoto, Yasuhiko Tabata, Yashito Ikada
• Format: Article
• Language: English
• Subjects: Adhesives; Amoxicillin - administration & dosage; Amoxicillin - pharmacology; Amoxicillin - therapeutic use; Amoxicillin Gelatin Microsphere Modified Gelatin Mucoadhesion; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Drug Delivery Systems; Fluorescent Dyes; Gastric Mucosa - metabolism; Gelatin - chemistry; Helicobacter Infections - drug therapy; Helicobacter pylori; Helicobacter pylori - drug effects; Male; Microspheres; Particle Size; Penicillins - administration & dosage; Penicillins - pharmacology; Penicillins - therapeutic use; Rats; Rats, Wistar
• ISSN: 0049-8254; 1071-7544; 1366-5928; 1521-0464
• DOI: 10.1080/107175400455173

Gastric mucoadhesive drug delivery systems are very promising for eradication of Helicobacter pylori (H. pylori), a spiral bacterium that resides in the gastric mucus layer and at the mucus- epithelial cell interface. New positively charged biodegradable microspheres were prepared using aminated gelatin by surfactantfree emulsification in olive oil, followed by a cross-linking reaction with glutaraldehyde. The amino group contents of the modified gelatin and the microspheres were determined using a 2,4,6-trinitrobenzenesulfonic acid method. With the increase of glutaraldehyde concentration, the amino group content of the microspheres decreased accordingly. The influence of glutaraldehyde concentration, cross-linking reaction time, drug-loading patterns, and type of release media on the in vitro release characteristics of amoxicillin from the microspheres was investigated. Amoxicillin release rate from the modified gelatin microspheres was significantly reduced compared with that from gelatin microspheres. Furthermore, the release was decreased with the increase of glutaraldehyde concentration and/or cross-linking time. On the other hand, a faster release was observed in a lower pH release medium and/or using a lower pH solution for amoxicillin loading. The gastric mucoadhesive properties of the microspheres were evaluated using RITC-labeled microspheres in an isolated rat stomach. The gastric mucoadhesion of the modified gelatin microspheres was markedly improved compared with that of gelatin microspheres. The modified gelatin microsphere proves to be a possible candidate delivery system for the effective eradication of H. pylori.