Abstract
BackgroundIntracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy.Methods and findingsWe have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo.ConclusionsIn this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.
Highlights
Antimicrobial peptides (AMPs) have gained interest as potential host directed therapeutic strategies against various infections
In this study we found that loading the antimicrobial peptide NZX into mesoporous silica particles (MSPs) increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model
Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis
Summary
Antimicrobial peptides (AMPs) have gained interest as potential host directed therapeutic strategies against various infections. Defensins comprise one of the largest groups of host defence peptides and are the best studied in infection models [1]. These cysteine-rich, cationic peptides act through disruption of microbial membranes, they may have additional host-related immune-modulating activities [2, 3]. Peptides are potentially degradable and need to be protected in order to safely reach the site of infection where they can exercise their mode of action [4]. To overcome these challenges, peptides can be delivered efficiently by encapsulating them in carrier systems, such as nanoparticles. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy
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