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

Abstract

The Gram-negative bacterium <i>Helicobacter pylori</i> 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 <i>H. pylori</i> 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 low-molecular-weight (DexS40-NC) or high-molecular-weight (DexS500-NC) dextran sulfate, or positively charged chitosan (CS_HMC+30-NC). The oil core of all NC formulations was also loaded with curcumin, a model lipophilic phytochemical substance with well-documented anti-inflammatory and anti-tumor activities. Our proof-of-principle experiments showed that the DexS40-NC formulation inhibited the adhesion of <i>H. pylori</i> 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 CS_HMC+30-NC was not clear-cut 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 <i>H. pylori</i> infections.