Targeting and killing the Ever-Challenging ulcer bug

Treating Helicobacter pylori (H. pylori) infections has been a never-ending challenge, which has contributed to the high incidence of gastric cancer. The antibiotics commonly used are not reaching the infection site in its active state and in a concentration high enough to effectively kill the bacteria. In this context, amoxicillin-loaded lipid nanoparticles with carefully chosen materials were developed, namely dioleoylphosphatidylethanolamine (DOPE) as a targeting agent and Tween®80 and linolenic acid as antimicrobial agents. This work shows the ability of these nanoparticles in (i) targeting the bacteria (imaging flow cytometry) and inhibiting their adhesion to MKN-74 cells (bacteria-gastric cells adhesion model); (ii) killing the bacteria even as an antibiotic-free strategy (time-kill kinetic studies, scanning electron microscopy, and bacterial membrane permeability studies); (iii) overcoming gastrointestinal features using a newly developed in vitro infection model that includes both physical (epithelial cells and mucus) and the chemical (acid medium) barriers; and in (iv) being incorporated in a floating system that can increase the retention time at the stomach. Overall, this work presents an effective nanosystem to deal with the ulcer-bug. Besides, it also provides two innovative tools transferable to other fields – an in vitro infection model and a floating system to incorporate nanoparticles