Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.
Bottom Line: Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs.Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments.Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.
Affiliation: Department of Pharmacology and Experimental Neuroscience, and.Show MeSH
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Mentions: To determine the subcellular localization of the nanoformulations, MDMs treated with fluorescein-labeled INHP and RIF NPs for 8 h were probed with antibodies to Rab 5 (early), 7 (late), 11 (slow recycling) and 14 (fast recycling) endosomal compartments. Colocalization of NPs and Rab compartments was determined by confocal microscopy. Confocal imaging showed both INHP (Fig. 4) and RIF (Fig. 5) NP distribution throughout the cytoplasm, colocalizing with late (Rab 7) and recycling (Rab 11 and 14) endosomal compartments.
Affiliation: Department of Pharmacology and Experimental Neuroscience, and.