Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 53, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2019.101170
Keywords
Rifampicin; Soluplus; Polymeric micelles; Tuberculosis; Respirable nanocarriers; Mycobacterium tuberculosis
Categories
Funding
- Universidad de Buenos Aires [UBACyT UBACYT 20020170100362BSA]
- CONICET
- CONICET, Argentina
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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 mull-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 (similar to 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 (Tc-99m) 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.
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