Antibiotic-loaded Nanomotors For The Treatment Of Helicobater Pylori Infections

Helicobacter pylori（Hp） infection is difficult to treat due to gastric acid,gastric mucus,biofilm barrier and drug resistance.Conventional antibiotics would be destroyed by strong acid and enzymes in the gastric environment,resulting in reduced drug activity or even complete inactivation,and the gastric emptying mechanism results in a very short residence time of the drug in the stomach.The rapid clearance mechanism of the mucus layer prevents drugs and drug delivery agents from reaching the epithelial surface.The mucus layer could hinder the passage of substances through steric hindrance and interaction forces.The short residence time and destruction in gastric acid,and the obstruction of the mucous layer of antibiotic result in insufficient concentration to reach the gastric mucosal layer where the Hp colonizes.At the same time,dense extracellular polymeric substances（EPS）of biofilm are present and drug access is restricted.Therefore,the dosage of antibiotics needs to be increased,which may lead to the development of bacterial resistance.So,it is urgent to design a preparation that can protect the drug from the destruction of gastric acid while enhancing the penetration of the drug in the gastric mucus and biofilm.Micro-nanomotors have attracted research interest in many fields,and the self-propelled properties can enhance penetration in gastric acid,gastric mucus,biofilm and other barriers.In the current study,Janus nanomotors were designed with Ca O₂ as the power source,and polydopamine（PDA）as the surface modification.And clarithromycin（CLR）is wrapped in the PDA layer through hydrogen bond interaction to form drug-loaded nanomotors.Eventually,about half of the cores surface coated with PDA to forming Janus nanomotors（J-Ca/Si@PDA-CLR）were identified for subsequent experiments.Scanning electron microscope showed the Janus structure of the nanomotors,and the size of J-Ca/Si@PDA-CLR was approximately 235nm.The experimental results showed that the nanomotor had no obvious cytotoxicity to AGS cells.And the in vitro drug release experiment results showed that CLR could be effectively loaded and released.The nanomotors had enhanced motion effects in gastric acid,gastric mucus and biofilms simulations,and maintained kinetic energy for a long time.The results of biofilm penetration showed that the nanomotors had excellent biofilm penetration characteristics,which could penetrate and distribute in the deep biofilm.In vitro anti-biofilm experiments showed that the structure of the biofilm was well destroyed by the nanomotors,and the therapeutic effect was concentration-dependent,and most bacteria in the biofilm were effectively killed with the integrity of the bacteria destroyed.The model of Hp infection was established in vivo,the results showed that the nanomotors could carry drugs through gastric mucus.The self-propulsion increased the penetration and retention in stomach,and resulted in the accumulation of drugs in biofilm,thereby better killed the bacteria in the deep biofilm.The nanomotors showed improved anti-biofilm effects in both in vitro and in vivo models with no significant toxicity.This work represents an enhenced penetration therapeutic strategy by nanomotors in mucus-associated biofilm infections and provides new ideas for practical biomedical applications of micro/nanomotors.