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: Uptake and retention of nanoformulated drugs were compared with that of NDs in MDM. As illustrated in Fig. 1D, G, cell uptake of nanoformulated drugs was 3-fold higher for INHP and 10-fold higher for RIF than uptake of NDs. The nanoformulations were retained in the cells for up to 15 d (Fig. 1E, H) with drug levels of 0.2 μg/106 cells for INHP and 0.1 μg/106 cells for RIF at d 15; in contrast, the NDs were not detectable after the first 24 h. To determine the RIF concentration that would provide maximum cell uptake, we treated MDM with 200 to 400 μM nanoformulated RIF. As shown in Fig. 2A, treatment with 300 and 400 μM provided similar cell drug levels. At 2, 4, and 8 h, MDM uptake of 300 and 400 μM RIF NPs was 2-fold higher than that for 200 μM.
Affiliation: Department of Pharmacology and Experimental Neuroscience, and.