Title : Targeting intracellular mycobacteria using nanosized niosomes loaded with antibacterial agents
Objectives. Pathogenic intracellular mycobacteria are difficult to treat because of the waxy and complex cell wall that characterizes the genus. Niosomes are vesicles with biomimetic cell membrane composition, which allow them to easily bind to the eukaryotic cells and deliver their cargo into the cytoplasm. The objectives of this study were the development of a new platform based on niosomes loaded with antimicrobial agents to target intracellular mycobacteria.
Methods. We fabricated nanoniosomes and loaded them with two antibiotics and lignin-silver-nanoparticles (L-AgNPs). The antibacterial activity of these nanoniosomes was tested against the intracellular pathogen Mycobacterium abscessus used as a model of infection of human macrophages THP-1 cells. The cytotoxicity and the immunological response of the antibacterial agents were tested on THP-1 cells using MTT assay and the secretion of pro- and anti-inflammatory cytokines, respectively. In addition, the proliferation of murine macrophages was measured by the incorporation of BrdU on de novo synthesized DNA.
Results. M. abscessus was susceptible to the antibiotic- and L-AgNP-loaded nanoniosomes in infected THP-1 macrophages, suggesting internalization of the vesicles as a result of fusion to the cellular membrane. Moreover, nanoniosomes showed no upregulation of pro-inflammatory cytokines when exposed to THP-1 macrophages.
Conclusions. Nanoniosomes loaded with antimicrobial agents improved drug efficacy while decreasing toxicity and should be considered for further testing in the treatment of intracellular pathogenic mycobacteria or as a new platform for precise intracellular delivery of drugs.
Audience take away:
• Nanoniosomes are novel vesicles easy to produce and represent a novel platform to treat bacterial infections, especially those produced by intracellular microorganisms.
• Nanoniosomes may be a topic of research to different faculties, including Pharmaceutical Sciences, Infectious Diseases, Respiratory Medicine, etc. In addition, this platform can be developed by pharma companies as a new delivery system to precisely target intracellular pathogens.
• Intracellular mycobacteria are pathogen difficult to eradicate. For example, Mycobacterium tuberculosis resides within alveolar macrophages. Then, this pathogen can be targeted by co-encapsulation of antibiotics and nanoparticles.
• The formulation of nanoniosomes can be delivered through inhalation, avoiding the use of systemic therapies.