Antimicrobial\nPeptide Hydrogel with pH-Responsive\nand Controllable Drug Release Properties for the Efficient Treatment\nof Helicobacter pylori Infection

Helicobacter pylori is the primary\ncause of gastric adenocarcinoma, which afflicts more than half of\nthe world’s population and seriously affects human health.\nHowever, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral\nadministration remains a challenge due to the harsh microenvironment,\nshort drug retention time, and physiological barriers in the stomach.\nMoreover, H. pylori has shown resistance\nto many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit\nsubstantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting\ntheir potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and\nsynthesis of an AMP (GE33) hydrogel with pH-responsive and controlled\npeptide release properties, in which the minimal inhibitory concentration\nof the AMP against H. pylori is as\nlow as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel\nunder neutral pH conditions but decomposes into monomers or oligomers\nunder acidic conditions. Upon oral administration of the hydrogel,\nthe acidic gastric environment would facilitate rapid release of active\nAMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the\nremaining peptide is protected in the hydrogel, extending its retention\ntime in the stomach, so that persistent drug release is achieved.\nThe controlled and sustained release manner of the active molecule\nGE33, which enhances drug bioavailability, along with its excellent\nbactericidal efficacy opens a great potential for treating H. pylori infection.