6533b829fe1ef96bd128a5f3

RESEARCH PRODUCT

Development of a new indole derivative dry powder for inhalation for the treatment of biofilm-associated lung infections

Styliani XiroudakiSamuele SabbatiniCamilla PecoraroStella CascioferroPatrizia DianaNathalie WauthozCinzia AntognelliClaudia MonariStefano GiovagnoliAurélie Schoubben

subject

Anti-biofilmChitosanLeucineCell viability studySpray-dryingPharmaceutical ScienceDesign of experiments

description

The aim of this work was to produce an inhalable dry powder formulation of a new anti-biofilm compound (SC38). For this purpose, chitosan was used as a polymeric carrier and l-leucine as a dispersibility enhancer. SC38 was entrapped by spray-drying into previously optimized chitosan microparticles. The final formulation was fully characterized in vitro in terms of particle morphology, particle size and distribution, flowability, aerodynamic properties, anti-biofilm activity and effects on lung cell viability. The SC38-loaded chitosan microparticles exhibited favorable aerodynamic properties with emitted and respirable fractions higher than 80 % and 45 % respectively. The optimized formulation successfully inhibited biofilm formation at microparticle concentrations starting from 20 μg/mL for methicillin-sensitive and 100 μg/mL for methicillin-resistant Staphylococcus aureus and showed a relatively safe profile in lung cells after 72 h exposure. Future in vivo tolerability and efficacy studies are needed to unravel the potential of this novel formulation for the treatment of difficult-to-treat biofilm-mediated lung infections.

10.1016/j.ijpharm.2022.122492https://hdl.handle.net/11391/1538073