An inhalable nanoparticle enabling virulence factor elimination and antibiotics delivery for pneumococcal pneumonia
Huiyue Dong1, Yuxin Zhao1, Shihong Li2
1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Abstract:
Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through antibiotics. However, the limited delivery of antibiotics and the undetoxified hydrogen peroxide (H2O2) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H2O2 virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells apoptosis by catalyzing the decomposition of accumulated H2O2 in the infected lung tissues. In synergy with antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional antibiotic treatment, highlighting its potential clinical application prospects.
Insights
A novel inhalable nanoassembly delivers antibiotics and neutralizes hydrogen peroxide to treat Streptococcus pneumoniae pneumonia. This dual-action approach enhances treatment efficacy and improves survival rates in pneumonia models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Infectious Diseases
Background:
- Streptococcus pneumoniae causes community-acquired pneumonia.
- Antibiotic delivery and hydrogen peroxide are key challenges in pneumonia treatment.
- Current therapies have limitations in effectively combating S. pneumoniae.
Purpose of the Study:
- To develop an inhalable nanoassembly for targeted drug delivery and virulence factor neutralization.
- To investigate the therapeutic potential of catalase-tannic acid nanoassembly with levofloxacin for pneumococcal pneumonia.
- To overcome limitations of conventional antibiotic treatments for pneumonia.
Main Methods:
- Formulation of an inhalable catalase (CAT)-tannic acid (TA) nanoassembly loaded with levofloxacin (CT@LVX).
- Evaluation of CT@LVX mucoadhesion and accumulation in lung tissues.
- Assessment of CAT's efficacy in neutralizing hydrogen peroxide and reducing apoptosis.
- In vivo testing in a Streptococcus pneumoniae pneumonia mouse model.
Main Results:
- CT@LVX demonstrated effective mucoadhesion and lung accumulation.
- Catalase activity reduced alveolar epithelial cell apoptosis by decomposing H2O2.
- Combined antibiotic and H2O2 neutralization led to decreased lung injury and inflammation.
- Achieved 100% survival rate in pneumonia-induced mice.
Conclusions:
- The CT@LVX nanoassembly offers a promising dual-action strategy for treating pneumococcal pneumonia.
- This approach effectively delivers antibiotics locally and neutralizes bacterial virulence factors.
- CT@LVX shows superior therapeutic outcomes compared to traditional antibiotic treatments, indicating clinical potential.
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