How to manage Helicobacter pylori infection beyond antibiotics: The bioengineering quest

The rise in antibiotic resistance rate challenges the effective treatment of various bacterial infections. One of them is the gastric infection caused by Helicobacter pylori, a Gram-negative bacterium responsible for several gastric disorders, as peptic ulcer, and close to 90 % of all gastric cancer cases. Available treatments, combining at least 3 antibiotics, fail in up to 40 % of the patients, prompting the need for newer therapies. Bioengineered strategies, namely using biomaterials in the form of micro/nanoparticles (MP/NP) have been explored for gastric infection management either as (i) "H. pylori binders", to bind H. pylori in the stomach and remove it by the gastrointestinal tract; (ii) contact killing agents, to destroy H. pylori in situ; or (iii) drug delivery systems, to transport and release antimicrobial compounds at the infection site. These MP/NP were prepared using different biomaterials, such as natural polymers (chitosan alone or combined with heparin, alginate or gelatin), lipids (phospholipids, cholesterol), metals (gold, silver) and inorganic compounds (zinc oxide). These biomaterials were selected due to their intrinsic antimicrobial properties, ability to produce pH responsive delivery systems or to encapsulate lipophilic compounds. Antimicrobial peptides (MSI-78 and MSI-78A), plants extracts (berberine, aloe vera, curcumin), bacteria-derived compounds (azurin, rhamnolipids) and polyunsaturated fatty acids (linoleic acid, docosahexaenoic acid), encapsulated or immobilized onto MP/NP, have been studied as alternative to antibiotics against H. pylori. Moreover, MP/NP targeting H. pylori were also developed by the bioconjugation of specific adhesin or lectin-binding glycans. In this review, the rational for each strategy, as well as their production method, mechanism of action and state of development is discussed to highlight where do we stand in this bioengineering quest against H. pylori.