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Nanometric ion pair complexes of tobramycin forming microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

  • Autori: Sardo, C.; Di Domenico, E.; Porsio, B.; De Rocco, D.; Santucci, R.; Ascenzioni, F.; Giammona, G.; Cavallaro, G.
  • Anno di pubblicazione: 2019
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: Biofilms; Cystic fibrosis artificial mucus (CF-AM); Ion-pair complex; Pseudomonas aeruginosa infections; Tobramycin; α,β-Poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA)
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Sustained pulmonary delivery of tobramycin from microparticles composed of drug/polymer nanocomplexes offers several advantages against traditional delivery methods. Namely, in patients with cystic fibrosis, microparticle delivery can protect the tobramycin being delivered from strong mucoadhesive interactions, thus avoiding effects on its diffusion toward the infection site. Polymeric ion-pair complexes were obtained starting from two synthetic polyanions, through impregnation of their solid dissociated forms with tobramycin in aqueous solution. The structure of these polymeric systems was characterized, and their activities were examined against various biofilm-forming Pseudomonas aeruginosa. Once dried, the nanocomplexes can change their aggregation state, to form microparticle-based aggregates with a spherical shape and a micrometer size. In aqueous dispersions, the ion-pair complexes produced had nanometric size, negative ζ potential, and high biocompatibility toward human bronchial epithelium cells. The antibiofilm activity of these formulations was more efficient than for free tobramycin, with the antibiofilm activity against P. aeruginosa mucoid and nonmucoid end-stage strains isolated from cystic fibrosis lungs being of particular relevance.