Targeted and efficient delivery of rifampicin to macrophages involved in non-tuberculous mycobacterial infection via mannosylated solid lipid nanoparticles

Abstract

Non-tuberculous mycobacterial infections are representative difficult-to-cure lung diseases with high incidence. Conventional treatments have several limitations such as negative side effects and increased drug resistance due to long-term administration. To overcome these limitations, there is a growing need for more stable drug delivery systems. Among the various drug delivery platforms developed thus far, solid lipid nanoparticles can be effectively loaded with hydrophobic substances and their physicochemical properties can be easily manipulated through surface modification, which makes them highly suitable drug delivery materials. Recent studies have reported the successful development of nanoparticles capable of selectively delivering drugs by targeting lectin-like receptors overexpressed on the surface of immune cells. Among these lectin-like receptors, the mannose receptor is a promising target because it is expressed on the surface of macrophages and is involved in immune activity. This study sought to synthesize rifampicin-loaded mannose surface-modified solid lipid nanoparticles (Man-RIF SLNs). The Man-RIF SLN synthesis process was first optimized, after which the characteristics of the synthesized particles were analyzed using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The surface modification with mannose was confirmed through FT-IR analysis. More importantly, the synthesized Man-RIF SLNs exhibited antibacterial and anti-biofilm properties against Mycobacterium intracellulare, a causative agent of non-tuberculous lung disease. Therefore, this study demonstrated that mannose receptor-targeted rifampicin delivery through solid lipid nanoparticles can be effectively applied to the treatment of non-tuberculous lung disease. Moreover, Man-RIF SLNs could also be used for the targeted delivery of drugs to several types of carcinoma cells or immune cells, as well as to treat lung diseases.