We incorporated a near-infrared (NIR) fluorescent dye, indocyanine green (ICG), in amine-modified layered double hydroxide nanoparticles (LDHs) by electrostatic attractions to render LDHs-ICG as an efficient NIR contrast agent for in vivo optical imaging. The further coating of chitosan on the external surfaces of LDHs-ICG was achieved through the cross-linking of amine-modified LDHs and different amounts of chitosan by using glutaraldehyde (GA) as a cross-linked agent. The hybridization of this organic-inorganic nanocomposite produced an efficient NIR optical contrast agent because the adsorbed ICG molecules were stabilized in the layered structures of LDHs to prevent them from leaching and/or metabolizing in physiological conditions. The cell viability and hemolysis assay also showed low cytotoxicity and low release of hemoglobin from the cell lysis of red blood cells (RBCs). The in vivo biodistribution results demonstrated that the coating of LDHs with different amounts of chitosan can develop organ-specific drug delivery systems, which can efficiently regulate the nanoparticle accumulation in various organs with un-coated LDHs-ICG targeting the liver and spleen, mono-chitosan-coated LDHs-ICG targeting the lungs, double chitosan-coated LDHs-ICG targeting the lungs and liver, and trimethylammonium (TA) modified double chitosan-coated LDHs-ICG samples targeting the liver. In addition to the high potential for the employment of chitosan-coated LDHs-ICG samples for developing contrast agents for in vivo imaging, the LDH nanoparticles can deliver therapeutic drugs to desired target organs by controlling the coating amounts of chitosan. Therefore, this approach can improve efficiency for traditional cancer diagnosis and cancer chemotherapy.
Background
Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High‐dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first‐line therapy for H. pylori eradication, and factors that affect the curing rate.
Methods
This is a single‐center, prospective, open‐label, randomized‐controlled trial. Naive patients (n=292) were randomly treated with bismuth‐containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13C‐urea breath test.
Results
In per‐protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention‐to‐treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group.
Conclusions
Rabeprazole‐amoxicillin dual therapy is equally effective to the bismuth‐containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non‐smoking condition, which deserves future stratified analysis for refinement and optimization.
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