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.

Graphical AbstractWe describe macrophage-aimed nanoparticle delivery system for antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. We show that the nanoparticles are efficiently uptaken by macrophages, where they become very quickly associated with lysosomal compartment. Rifampicin release from the nanoparticles is surprisingly very significantly faster in macrophages than in vitro. After drug release, the nanoparticles in macrophages are enzymatically degraded with half-life 88 ± 11 min.132