Polysaccharides as Bacterial Antiadhesive Agents and “Smart” Constituents for Improved Drug Delivery Systems Against Helicobacter pylori Infection

Abstract

The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context, the exploration of the biological activity of plant-derived products or polysaccharides commonly present in foods is increasingly becoming more and more attractive. This review aims to present the current state-of-the-art on the antiadhesive capacity of different polysaccharide families, on polysaccharide-based nanosystems and the proof-of-concept evidence of their potential use as alternative medicines against H. pylori.

Innovative Methods and Applications in Mucoadhesion Research

“…Besides their ability to inhibit the bacterial growth completely and to be more stable than normal liposomes, they also appeared to prevent the adhesion of H. pylori to a cell monolayer and gastric tissue section . The concept of plug‐and‐seal as an approach to prevent bacterial infection is the topic of intense research of discovery of new potential inhibitors (e.g., polysaccharide) and their usage as anti‐adhesive preparation …”

“…[243] The concept of plug-and-seal as an approach to prevent bacterial infection is the topic of intense research of discovery of new potential inhibitors (e.g., polysaccharide) and their usage as anti-adhesive preparation. [244] Due to the presence of adhesines on H. pylori surface able to recognize fucose-bearing antigens on the epithelial/mucosal surface, fucose has been introduced in nanoformulation as targeting moiety. Ramteke et al used a carbodiimide method to covalently conjugate fucose to chitosan.…”

Electrospinning and crosslinking of polyvinyl alcohol/chitosan composite nanofiber for transdermal drug delivery

“…[14][15][16][17] Furthermore, CS is reported to have pharmacological properties including wound healing accelerator, [18] hyphcholesterolemic action, [19] antacid and antiulcer activity. [14][15][16][17] Furthermore, CS is reported to have pharmacological properties including wound healing accelerator, [18] hyphcholesterolemic action, [19] antacid and antiulcer activity.…”

“…CS as a linear β-1, 4-linked polysaccharide produced from deacetylation of chitin have been widely used in biomedical application because of their outstanding properties, such as non-toxicity, biodegradability, antibacterial, wound healing property, hemostatic activity and high-permeability. [14][15][16][17] Furthermore, CS is reported to have pharmacological properties including wound healing accelerator, [18] hyphcholesterolemic action, [19] antacid and antiulcer activity. [20] CS has been used in biomaterial engineering for drug delivery system in forms of films, [21] microspheres, [22] hydrogels [23] and nanofibers.…”

Electrostatic self-assembly of polysaccharides into nanofibers

“…1a). Chitosan's are positively charged polysaccharides, consisting of glucosamine linked to N-acetyl glucosamine units, that can exhibit several biological properties such as biocompatibility, biodegradability, hemostatic activity, antibacterial, antimycotic and anticoagulant activity [11][12][13][14]. Chitosan oligomers (ChO) are a class of water-soluble chitosan(s) with relatively low molecular weight obtained by the depolymerization of Chitosan(s), comprising also a set of bioactive properties [15] (Fig.…”