Recently, achieving accurate and efficacious disease targeting with minimal off-target effects is of paramount importance in designing diagnostic and therapeutic agents for tuberculosis. In this respect, nanocarriers have gained enormous popularity because of their attainable multifunctional features, as well as tuberculosis-targeting potential. The development and application of nanoparticles as in vivo delivery vehicles for therapeutic and/or diagnostic agents has seen a drastic growth over the last decades. Novel imaging techniques allow real-time in vivo study of nanoparticle accumulation kinetics at the level of the cell and targeted tissue. Successful intravenous application of such nanocarriers requires a hydrophilic particle surface coating, of which polyethylene glycol (PEG) has become the most widely studied and applied. In the current study, the effect of nanoparticle PEG surface density on the targeting efficiency of ligand-functionalized nanoemulsions was investigated. We synthesized 100 nm nanoemulsions with a PEG surface density varying from 5 to 40 mol%. The development of a unique experimental imaging setup allowed us to study, in real time, nanoparticle accumulation kinetics at (sub)-cellular resolution in tuberculosis that were grown in a window chamber model with confocal microscopy imaging, and at the macroscopic tuberculosis level in subcutaneously grown xenografts with magnetic resonance imaging. Accumulation in the tuberculosis occurred more rapidly for the targeted nanoemulsions than for the non-targeted versions, and the PEG surface density had a strong effect on nanoparticle targeting efficiency. Counter intuitively, yet consistent with the PEG density conformation models, the highest specificity and targeting efficiency was observed at a low PEG surface density.

Effect of nanoparticle polyethylene glycol surface density on ecumicin: Toward redesigning the PEG surface of nanocarriers for drug delivry

256th National Meeting (2018)

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