Pulmonary delivery of rifampicin-loaded soluplus micelles against Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) stands as the second “most deadly infectious disease” behind AIDS. Rifampicin (RIF) represents one of the most effective anti-TB drugs of the “short-term” oral TB therapy. However, the main limitations of the oral treatment are related with the lack of patient adherence and the development of multi-drug resistant Mycobacterium tuberculosis (Mtb) strains. Recently, the pulmonary administration of anti-TB drugs has become an attractive alternative to improve TB therapy. Hence, we have developed a respirable nanocarrier based on RIF-loaded polymeric micelles (PMs), employing a commercially available graft-copolymer of poly (vinyl caprolactam)-poly (vinyl acetate)-poly (ethylene glycol) (Soluplus). The RIF apparent aqueous solubility was increased (14.3-fold) and the micellar system was ranged in the nanoscale (~107 nm). Then, according to its in vitro aerodynamic behavior, our nanoformulation represented a suitable system for deep lung drug delivery. Interestingly, these inhalable RIF-loaded PMs enhanced (up to 2.5-fold) the in vitro drug microbicidal activity in Mtb-infected THP-1 macrophages versus a RIF solution. In addition, the biodistribution studies of the radiolabelled (99mTc) PMs demonstrated their lung accumulation over 24 hs in rats. Overall, this novel nanoformulation stands as an attractive platform for a potential inhalable TB therapy.