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Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.

Edagwa BJ, Guo D, Puligujja P, Chen H, McMillan J, Liu X, Gendelman HE, Narayanasamy P - FASEB J. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Neuroscience, and.

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Related in: MedlinePlus

Subcellular localization of RIF NPs. MDMs were treated with 300 μM dye-labeled RIF NPs for 8 h. Cells were fixed with PFA and probed with antibodies to Rab 5 (A), Rab 7 (B), Rab 11 (C), or Rab 14 (D). Primary antibodies were detected with Alexa Fluor 488-labeled secondary antibody. Nanoparticles are shown in red, cell compartments in green, nuclei in blue, and overlay of the compartment and particle in yellow.
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Figure 5: Subcellular localization of RIF NPs. MDMs were treated with 300 μM dye-labeled RIF NPs for 8 h. Cells were fixed with PFA and probed with antibodies to Rab 5 (A), Rab 7 (B), Rab 11 (C), or Rab 14 (D). Primary antibodies were detected with Alexa Fluor 488-labeled secondary antibody. Nanoparticles are shown in red, cell compartments in green, nuclei in blue, and overlay of the compartment and particle in yellow.

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.


Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.

Edagwa BJ, Guo D, Puligujja P, Chen H, McMillan J, Liu X, Gendelman HE, Narayanasamy P - FASEB J. (2014)

Subcellular localization of RIF NPs. MDMs were treated with 300 μM dye-labeled RIF NPs for 8 h. Cells were fixed with PFA and probed with antibodies to Rab 5 (A), Rab 7 (B), Rab 11 (C), or Rab 14 (D). Primary antibodies were detected with Alexa Fluor 488-labeled secondary antibody. Nanoparticles are shown in red, cell compartments in green, nuclei in blue, and overlay of the compartment and particle in yellow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232285&req=5

Figure 5: Subcellular localization of RIF NPs. MDMs were treated with 300 μM dye-labeled RIF NPs for 8 h. Cells were fixed with PFA and probed with antibodies to Rab 5 (A), Rab 7 (B), Rab 11 (C), or Rab 14 (D). Primary antibodies were detected with Alexa Fluor 488-labeled secondary antibody. Nanoparticles are shown in red, cell compartments in green, nuclei in blue, and overlay of the compartment and particle in yellow.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Neuroscience, and.

Show MeSH
Related in: MedlinePlus