Bioresorbable polymer structures - promising carriers for prolonged forms of anti-tuberculosis drugs

<b>Background:</b> Development of new anti-TB drug delivery systems is an urgent problem in the treatment of tuberculosis. Such systems allow patients to remain complied to long courses of MDR-TB therapy. We developed bioresorbable polymeric carriers encapsulated by levofloxacin (LFX). <b>Objective:</b> to create structures with controlled release of levofloxacin and to evaluate its release rate from different polymer carriers. <b>Methods:</b> 10 wt% LFX (Sigma-Aldrich) was encapsulated into Polylactoglicolyde (PLG) (PDLG7502, Purac) by supercritical fluid technologies (SCF) using supercritical carbon dioxide. Different microparticles (from 5 to 100 mkm) and scaffolds were formed. The LFX release rate was evaluated on M. tuberculosis H37Rv (MTB) culture an in vitro model. <b>Results:</b> In vitro model for studying LFX release kinetics was developed. The model was based on the estimation of the time to growth MTB in liquid media with addition of solution in which a polymer carrier (with LFX included) was incubated for a different time. The amount of LFX released was determined by comparing the MTB growth inhibition in tubes containing released LFX from polymer carrier and the MTB growth inhibition in control tubes containing different concentrations of pure LFX (0.03-1.0 mkg/ml). It was shown that full release of LFX from microparticles occurs in the first hours of incubation (1-3 hours). However, for scaffolds, a slow gradual LFX release was recorded over 33 days. <b>Conclusions:</b> PLG-based structures formed by SCF technologies appear to be promising carriers for the development of controlled release LFX dosage forms. <b>Method:</b> FSRC “Crystallography and Photonics” RAS, RFBR №18-29-06062.