Pulmonary delivery of rifampicin-loaded Soluplus micelles against Mycobacterium tuberculosis

GROTZ, ESTEFANÍA; TATEOSIAN, NANCY; SALGUEIRO, JIMENA; BERNABEU, EZEQUIEL; LORENA GONZALEZ; MANCA, MARIA LETIZIA; AMIANO, NICOLAS; VALENTI, DONATELLA; MANCONI, MARIA; GARCIA, VERONICA; MORETTON, MARCELA A.; CHIAPPETTA, DIEGO A.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

EDITIONS SANTE

Lugar: Paris; Año: 2019 vol. 53

1773-2247

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) andthemicellar systemwasrangedinthenanoscale (~107nm).Then,accordingtoits 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 24hs in rats. Overall, this novel nanoformulation stands as an attractive platform for a potential inhalable TB therapy.