期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 13, 期 1, 页码 307-315出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2016.08.031
关键词
Tuberculosis; Rifampicin; Nanoparticle; MPEO-b-PCL; FRET
资金
- Norwegian Financial Mechanism [MSMT-28477/2014, 7F14009]
- Czech Science Foundation [15-10527J, P302/12/G157]
- Charles University in Prague [PRVOUK P27/LF1/1, UNCE 204022]
- OPPK [CZ.2.16/3.1.00/24010]
We have developed a biodegradable, biocompatible system for the delivery of the antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on poly(ethylene oxide) monomethyl ether-block-poly(epsilon-caprolactone) were noncovalently loaded with rifampicin, a combination that, to best of our knowledge, was not previously described in the literature, which showed significant benefits. The nanoparticles contain a Forster resonance energy transfer (FRET) system that allows real-time assessment of drug release not only in vitro, but also in living macrophages where the mycobacteria typically reside as hard-to-kill intracellular parasites. The fluorophore also enables in situ monitoring of the enzymatic nanoparticle degradation in the macrophages. We show that the nanoparticles are efficiently taken up by macrophages, where they are very quickly associated with the lysosomal compartment. After drug release, the nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88 +/- 11 min. (C) 2016 Elsevier Inc. All rights reserved.
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