Carboxymethyl chitosan and poly-γ-glutamic acid-based gastroretentive sponge with high swelling and mechanical stability for targeted eradication of Helicobacter pylori

Helicobacter pylori ( H. pylori ) is a globally prevalent bacterial pathogen associated with various gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. However, the effectiveness of oral medications is often compromised by the harsh gastric environment, leading to limited therapeutic outcomes. In this study, we developed a novel carboxymethyl chitosan/poly-γ-glutamic acid/polyvinyl pyrrolidone (CMCS/γ-PGA/PVP, CPP) sponge with a high swelling ratio and mechanical stability for gastric retention and targeted drug delivery. The CPP sponge demonstrated rapid swelling in acidic environments (38.16 g/g) and prolonged intragastric retention for up to 3 days while maintaining structural integrity under gastric peristalsis. Loaded with amoxicillin and ebselen, the CPP sponge significantly enhanced drug bioavailability and achieved a 98.59 % bacteriostasis ratio against H. pylori in a mouse model. Additionally, the sponge could alleviate gastric inflammation. The CPP sponge's triple-network structure, combining intramolecular amide bonds, intermolecular amide bonds, and hydrogen bonds, provided excellent mechanical stability and swelling properties. This study highlights the potential of the CPP sponge as an effective therapeutic platform for H. pylori infection, offering sustained drug release, improved gastric retention, and enhanced therapeutic efficacy.