The potential utility of chitosan micro/nanoparticles in the treatment of gastric infection

Abstract

Gastric infections are mainly caused by Helicobacter pylori (H. pylori), a bacterium that colonizes the gastric mucosa of over 50% of the world’s population. Chronic H. pylori infection has been associated with gastric diseases such as chronic gastritis, peptic ulcer and gastric adenocarcinoma. Current eradication treatment relies on antibiotic-based therapies that are unsuccessful in approximately 20% of the patients. Chitosan, a natural and cationic polysaccharide has been investigated in the treatment of H. pylori infection. Due to its mucoadhesive properties, it has been used in the form of micro/nanoparticles, polyelectrolyte complexes or coatings as antibiotic encapsulation systems for gastric delivery, but alternative molecules may also be incorporated. It has been recently proposed that chitosan can also be used for H. pylori binding and scavenging from the host stomach due to its antimicrobial/binding properties. In this manuscript, a brief description of the use of chitosan in H. pylori treatment is reviewed.

Keywords::

• biomaterials
• chitosan
• crosslinking
• drug delivery
• gastric cancer
• Helicobacter pylori
• microspheres
• mucoadhesion
• nanoparticles
• polyelectrolytes

Financial & competing interests disclosure

This paper has been financed by FEDER funds through Programa Operacional Factores de Competitividade – COMPETE and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia, in the framework of the projects PEst-C/SAU/LA0002/2013, NORTE-07-0124-FEDER-000005, FCOMP-01-0124-FEDER-020073 (PTDC/CTM-BPC/121149/2010) and FCOMP-01-0124-FEDER-041276 (EXPL/CTM-BIO/0762/2013) and grant SFRH/BD/89001/2012. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Helicobacter pylori (H. pylori) infects about half of the world’s population and its persistent infection is associated with a strong risk for the development of gastric adenocarcinoma.

• The failure of the current available antibiotic-based therapy (∼1 in each 5 patients) demonstrated the need of alternative treatments.

• Chitosan is a natural biocompatible polymer with great potential in H. pylori treatment, mainly due to its gastric retentive and antimicrobial properties, but also because it can easily be chemically modified.

• Chitosan properties are mainly related with its primary amine groups that are directly related with its degree of deacetylation.

• In H. pylori infection treatment, chitosan is mostly used as gastric drug delivery system, whether as crosslinked particles, as polyelectrolyte complexes with anionic polymers or as coatings. Nevertheless, it has recently been proposed as an H. pylori binding system.

• In order to prevent premature release of the encapsulated drug, chitosan particles must be crosslinked to avoid its fast dissolution in gastric acidic conditions.

• Polyelectrolyte complex-based chitosan particles can be pH-responsive, that is, particles are stable in acidic pH (drug preservation) and unstable at physiological pH to release the drug near H. pylori infection site (near gastric epithelial cells).

• Chitosan microspheres crosslinked with genipin have great potential as H. pylori-binding systems for the clearance of this bacterium from infected host through normal gastrointestinal tract since they can bind H. pylori, are noncytotoxic and are stable during all the digestive process.

• In order to increase their residence time in the stomach, chitosan particles can be conjugated with lectins to target the gastric mucosa through lectin-carbohydrate recognition.

• In order to be directed toward H. pylori, chitosan particles can be conjugated with fucose or glycans (Le^b, sLe^x, …) to target H. pylori adhesins.