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: The trafficking of the nanoformulations through endosomal compartments was compared with subcellular sites of mycobacterial replication. Endosomal compartments from drug-loaded and infected MDMs were immunoisolated using magnetic beads coated with antibodies to Rab 5, 7, 11, and 14 compartments (46). Drug and mycobacterium levels were determined in each compartment. As shown in Fig. 6, the RIF and INHP NPs were distributed mainly to late endosomal (Rab 7) and recycling endosomal (Rab 11 and Rab 14) compartments (Fig. 6B, C, respectively). Similarly, mycobacteria were found in all the endosomal compartments (Fig. 6D), with the majority in Rab 7 (late) and Rab 14 (fast recycling) endosomes. These data demonstrate that the drug NPs traffic to the same subcellular compartments where the mycobacterium replicates (Fig. 6B–D).
Affiliation: Department of Pharmacology and Experimental Neuroscience, and.