Precise unidirection delivery and site-specific release utilizing a nanocapsules-loaded mucoadhesive
5 affiliations
- 1Lab of Pharmaceutic, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
- 2Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China
- 3Med-X Center for Materials, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China; Corresponding authors.
- 4Lab of Pharmaceutic, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Corresponding authors.
- 5Lab of Pharmaceutic, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Sun Yat-sen University, Guangzhou 510006, China; State Key Laboratory of Anti-Infective Drug Discovery and Development, Sun Yat-sen University, Guangzhou 510006, China; Corresponding authors.
Abstract
Helicobacter pylori ( H. pylori ) infection disrupts the gastric microenvironment and promotes the development of gastric cancer and other gastrointestinal diseases. Despite the high prevalence of asymptomatic chronic infection and recurrent infections, persistent mucosal injury continues to drive early pathological alterations, including gastric epithelial remodeling and intestinal metaplasia, that may become irreversible beyond a “point of no return”. Although clinical antibiotic-based H. pylori eradication therapies reduce gastric cancer risk, their efficacy markedly diminishes once progressive gastric premalignant lesions developed, and long-term use often causes microbiome dysbiosis and antimicrobial resistance. To address these unmet clinical needs, we developed CurE-gel, an antibiotic-free smart in situ gel with pH- and lipase-cascade responsive drug release. This system enables targeted eradication of H. pylori while simultaneously facilitating gastric niche restoration. Composed of sodium alginate and polyacrylate, CurE-gel exhibits strong gastric mucosal adhesion and precise pH responsiveness. Utilizing the pathophysiological gastric pH gradient (luminal pH 1–2 vs. mucosal pH > 4), CurE-gel mediates unidirectional release of its encapsulated nanocapsules (CurE-cap) at the damaged mucosal side. Then, CurE-cap penetrates the mucus and accumulated at H. pylori colonies, where its polycaprolactone shell is hydrolyzed by bacterial lipase to release curcumin and eugenol. This system achieved: (i) targeted H. pylori eradication via biofilm disruption and virulence suppression; (ii) epithelial barrier protection and pathological progression suppression through virulence translocation inhibition, ROS scavenging, lipid peroxidation reduction and DNA damage mitigation; and (iii) gastric homeostasis restoration by recovery of tight junction proteins and gastric microbiota modulation. In vivo , CurE-gel achieved over 99% H. pylori eradication, reversed gastric progressive premalignant lesions and reconstructed a healthy gastric microbiota without systemic toxicity. By integrating mucoadhesive retention with pH- and lipase-cascade responsive drug release, this platform sets an innovative paradigm for two-pronged strategy in targeted H. pylori clearance and gastric homeostasis restoration, ultimately aiming to prevent gastric carcinogenesis.
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BibTeX
@article{chen2026precise,
title = {{Precise unidirection delivery and site-specific release utilizing a nanocapsules-loaded mucoadhesive}},
author = {Xiaonan Chen and Yuhan Fan and Jiabao Hao and Shuqi Zhang and Suqi Hao and Yingying Sun and Jing Li and Ling Zhang and Shihui Yu and Haiyan Hu},
journal = {Acta Pharmaceutica Sinica B},
year = {2026},
month = oct,
doi = {10.1016/j.apsb.2026.03.018},
url = {https://doi.org/10.1016/j.apsb.2026.03.018},
note = {CC BY},
}
RIS
TY - JOUR
TI - Precise unidirection delivery and site-specific release utilizing a nanocapsules-loaded mucoadhesive
AU - Xiaonan Chen
AU - Yuhan Fan
AU - Jiabao Hao
AU - Shuqi Zhang
AU - Suqi Hao
AU - Yingying Sun
AU - Jing Li
AU - Ling Zhang
AU - Shihui Yu
AU - Haiyan Hu
PY - 2026
DA - 2026/10/31
JO - Acta Pharmaceutica Sinica B
DO - 10.1016/j.apsb.2026.03.018
UR - https://doi.org/10.1016/j.apsb.2026.03.018
AB - Helicobacter pylori ( H. pylori ) infection disrupts the gastric microenvironment and promotes the development of gastric cancer and other gastrointestinal diseases. Despite the high prevalence of asymptomatic chronic infection and recurrent infections, persistent mucosal injury continues to drive early pathological alterations, including gastric epithelial remodeling and intestinal metaplasia, that may become irreversible beyond a “point of no return”. Although clinical antibiotic-based H. pylori eradication therapies reduce gastric cancer risk, their efficacy markedly diminishes once progressive gastric premalignant lesions developed, and long-term use often causes microbiome dysbiosis and antimicrobial resistance. To address these unmet clinical needs, we developed CurE-gel, an antibiotic-free smart in situ gel with pH- and lipase-cascade responsive drug release. This system enables targeted eradication of H. pylori while simultaneously facilitating gastric niche restoration. Composed of sodium alginate and polyacrylate, CurE-gel exhibits strong gastric mucosal adhesion and precise pH responsiveness. Utilizing the pathophysiological gastric pH gradient (luminal pH 1–2 vs. mucosal pH > 4), CurE-gel mediates unidirectional release of its encapsulated nanocapsules (CurE-cap) at the damaged mucosal side. Then, CurE-cap penetrates the mucus and accumulated at H. pylori colonies, where its polycaprolactone shell is hydrolyzed by bacterial lipase to release curcumin and eugenol. This system achieved: (i) targeted H. pylori eradication via biofilm disruption and virulence suppression; (ii) epithelial barrier protection and pathological progression suppression through virulence translocation inhibition, ROS scavenging, lipid peroxidation reduction and DNA damage mitigation; and (iii) gastric homeostasis restoration by recovery of tight junction proteins and gastric microbiota modulation. In vivo , CurE-gel achieved over 99% H. pylori eradication, reversed gastric progressive premalignant lesions and reconstructed a healthy gastric microbiota without systemic toxicity. By integrating mucoadhesive retention with pH- and lipase-cascade responsive drug release, this platform sets an innovative paradigm for two-pronged strategy in targeted H. pylori clearance and gastric homeostasis restoration, ultimately aiming to prevent gastric carcinogenesis.
SN - 2211-3835
SN - 2211-3843
ER -