System with embedded drug release and nanoparticle degradation sensor showing efficient rifampicin delivery into macrophages.
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(ε-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 Förster 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.
Institute of Macromolecular Chemistry AS CR, v. v. i., Heyrovsky sq. 2, Prague, Czech Republic.
Jiří
J
Trousil
Institute of Macromolecular Chemistry AS CR, v. v. i., Heyrovsky sq. 2, Prague, Czech Republic.
Sergey K
SK
Filippov
Institute of Macromolecular Chemistry AS CR, v. v. i., Heyrovsky sq. 2, Prague, Czech Republic. Electronic address: mhruby@centrum.cz.
Martin
M
Hrubý
Institute of Cellular Biology and Pathology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
Tomáš
T
Mazel
Institute of Cellular Biology and Pathology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
Zdeňka
Z
Syrová
Institute of Cellular Biology and Pathology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
Dušan
D
Cmarko
Institute of Cellular Biology and Pathology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
Silvie
S
Svidenská
Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.
Jana
J
Matějková
Institute of Cellular Biology and Pathology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
Lubomír
L
Kováčik
Institute of Macromolecular Chemistry AS CR, v. v. i., Heyrovsky sq. 2, Prague, Czech Republic.
Bedřich
B
Porsch
Institute of Macromolecular Chemistry AS CR, v. v. i., Heyrovsky sq. 2, Prague, Czech Republic.
Rafał
R
Konefał
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, Oslo, Norway.
Reidar
R
Lund
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, Oslo, Norway.
Bo
B
Nyström
Institute of Cellular Biology and Pathology, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic.
Ivan
I
Raška
Institute of Macromolecular Chemistry AS CR, v. v. i., Heyrovsky sq. 2, Prague, Czech Republic.
Petr
P
Štěpánek
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D031541:Fluorescence Resonance Energy Transfer; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D000067996:RAW 264.7 Cells; D012293:Rifampin / Q000008:administration & dosage*
D000995:Antitubercular Agents; D001672:Biocompatible Materials; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D012293:Rifampin
FRET; MPEO-b-PCL; Nanoparticle; Rifampicin; Tuberculosis