Nanoparticles of lactic acid polymer with rifampicin decrease activity of multi-drug transporter P-gp in human macrophages

Currently, the problem of effectiveness reduction of the anti-tuberculosis drugs is associated not only with the development of drug resistance by the pathogen, but also with the activity of the multidrug resistance protein P-gp (P-glycoprotein) of macroorganism cells. Rifampicin, the main anti-tuberculosis drug, is a substrate for P-gp. The article presents data on the activity of P-gp in pro-inflammatory human macrophages and assesses the effect of a new form of the anti-tuberculosis drug – rifampicin-loaded lactic acid polymer nanoparticles – on it. Scanning electron microscopy, laser confocal microscopy, MTT test and flow cytometry methods were used. It was shown that the new form of rifampicin is non-toxic for human monocytes and macrophages of the THP-1 cell line. In addition, it activates the processes of endocytosis/ phagocytosis and reduces the functional activity of P-gp. Thus, it seems promising to develop encapsulated anti-tuberculosis drugs – with phagocytosis-activating properties that specifically affect certain features of human macrophages.

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