Low-Molecular-Weight Dextran Sulfate Nanocapsules Inhibit the Adhesion of Helicobacter pylori to Gastric Cells

Abstract

The Gram-negative bacterium Helicobacter pylori is the most common bacterial pathogen in humans, infecting 24-79% of the population at any time. Standard eradication protocols involve multi-target therapy including combinations of antibiotics, which has promoted the emergence of resistant strains. To address this challenge, we prepared antibiotic-free colloidal nanoparticles designed to interfere with the adhesion mechanisms of H. pylori and thus prevent both the onset and recurrence of infection. Our colloidal particles comprised a nanocapsule (NC) formulation based on an oil-core nanoemulsion co-stabilized with lysozyme and lecithin, coated with negatively-charged lowmolecular-weight (DexS40-NC) or high-molecular-weight (DexS500-NC) dextran sulfate, or positively-charged chitosan (CSHMC+30-NC). The oil core of all NC formulations was also loaded with curcumin, a model lipophilic drug with well-documented documented anti-inflammatory and antitumor activities. Our proof-of-principle experiments showed that the DexS40-NC formulation inhibited the adhesion of H. pylori to AGS stomach cells in a dose-dependent manner. DexS40-NC achieved more potent inhibition than DexS500-NC or uncoated control nanoemulsions, whereas the effect of CSHMC+30-NC was not clearcut given the ability of this formulation to aggregate bacteria. DexS40-NC, unlike DexS500-NC, showed no cytotoxic effects against AGS, Caco-2, or MDCK cell lines. DexS40-NC is, therefore, a promising candidate for further development as an alternative or complementary therapy against H. pylori infections.

Smart drug delivery against Helicobacter pylori: pectin-coated, mucoadhesive liposomes with antiadhesive activity and antibiotic cargo

“…On the other hand, antiadhesive treatment could prevent new infections or recurrence, which is still a big problem in H. pylori clinical treatment, even after positive eradication therapy. For this, new strategies and targets should be considered, using innovative formulations, which increase the residence time of the antibacterial drug cargo in the stomach by interaction with the mucus layer, specifically interacting with bacterial virulence factors (Menchicchi et al 2019). Previous studies have shown that both anionic polysaccharides such as dextran sulfate and cationic ones such as chitosan can interact with mucins (Menchicchi et al 2015a) and some of these can also modulate adhesive interactions with H. pylori (Menchicchi et al 2015b).…”

Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice

“…Alternative therapies to overcome these challenges have been comprehensively explored [15][16][17][18]. Focus has been given to understanding bacterial infection mechanisms and interaction with the host [19,20], identifying bacterial specific molecules that may represent potential targets, such as bacterial virulence factors, urease, flagella or surface adhesins [21][22][23]. The combination of these targets with improved encapsulation systems for local delivery of antibiotics (using micro-or nano-systems) [24][25][26][27][28][29][30][31][32][33], usage of compounds from natural sources [34][35][36][37][38][39][40][41] or vaccination [42][43][44][45] has allowed the development of more precise and efficient systems aiming H. pylori eradication.…”