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Nebulized, macrophage-targeted, Linezolid-loaded lipid carriers for intracellular treatment of tubercular infections – In vitro/in vivo study

Effective treatment of tuberculosis (TB) demands progression control in line with TB elimination. The objective herein is to formulate nebulized targeted antitubercular - lipid nanocarriers for TB treatment. In this context, mannosylated solid lipid nanoparticles (MN-SLNs) incorporating LNZ (LNZ) we...

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Bibliographic Details
Published in:Journal of drug delivery science and technology 2024-11, Vol.101, p.106202, Article 106202
Main Authors: Makled, Shaimaa, Nafee, Noha, Okasha, Hadir, Boraie, Nabila
Format: Article
Language:English
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Summary:Effective treatment of tuberculosis (TB) demands progression control in line with TB elimination. The objective herein is to formulate nebulized targeted antitubercular - lipid nanocarriers for TB treatment. In this context, mannosylated solid lipid nanoparticles (MN-SLNs) incorporating LNZ (LNZ) were prepared and characterized. Their nebulization efficiency and cytotoxicity were appraised. Potential internalization of LNZ-MN-SLNs in alveolar macrophages (AM) was evaluated. In vivo biodistribution was carried out following orotracheal administration to mice. Susceptibility testing to investigate antitubercular activity of LNZ formulations against Mycobacterium tuberculosis (standard strain and clinical isolates) was performed. MN-SLNs ensured ≈930 nm diameter, 5–54 mV zeta-potential and 19 %w/v LNZ loading in addition to pH-independent sustained release. Jet nebulization showed 51 % nebulization efficiency within 20 min. Viability assay on MH-S cells warranted an IC50 
ISSN:1773-2247
DOI:10.1016/j.jddst.2024.106202