Hepatobiliary transported levofloxacin-loaded nanoparticles for treatment of bacterial biliary infection
Abstract
Biliary tract infections (BTIs) present significant therapeutic challenges due to limited antibiotic penetration into bile and the rising prevalence of multidrug-resistant pathogens. To address this, we developed a maltodextrin derivate based nanoparticle (MDNP) for enhanced antibiotic delivery to the biliary system. Levofloxacin (Lev) was efficiently loaded into MDNP (Lev-NP), forming monodisperse spherical nanoparticles (∼82 nm) with high drug loading (25.8% w/w). In vitro studies demonstrated minimal drug release under physiological conditions but rapid release (>90% within 1 h) in bile containing with H2O2 mimicking the infection environment. Following intravenous administration, Lev-NP exhibited significantly enhanced hepatobiliary distribution, achieving 6.9-fold higher maximum bile concentration and 3.3-fold greater biliary exposure compared to free Lev. In murine models, Lev-NP treatment achieved complete bacterial eradication in E. coli-induced biliary infections, as well as killing ratios of 85.9 ± 4.5% in bile and 98.6 ± 0.7% in the gallbladder in S. Typhi-induced biliary infections. These results significantly outperformed free Lev, which only transiently reduced bacterial loads. Comprehensive safety evaluations confirmed no significant systemic or organ toxicity. This study highlights a promising nanotherapeutic strategy to overcome the limitations of conventional antibiotic therapy for BTIs by leveraging hepatobiliary transited and stimuli-responsive drug…
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.