During Pilot project FFC#23/2017, lipid/polymer hNPs for sustained release at lungs of a siRNA pool against NF-kB have been successfully developed. The most adequate formulation conditions to produce non-PEGylated and PEGylated siRNA-loaded hNPs (hybrid nanoparticles) with optimal aerosolization and mucus-penetrating properties have been identified. Preliminary in vitro data suggest that siRNA-loaded hNPs are not cytotoxic and may penetrate lung extracellular barriers, allowing siRNA uptake inside human bronchial epithelial cells. Furthermore, a rat model of lung inflammation (challenged intratracheally with LPS from E. Coli) has been set up and validated to start in vivo efficacy studies. In the following FFC#25/2018 project, one or two optimized siRNA-loaded hNPs formulations will progress to assess the behavior upon contact with human CF sputum and human lung epithelial barrier models. Meanwhile, in vivo silencing efficacy will be assessed in inflamed rats. The development of a siRNA delivery system already engineered for in vivo inhalation and transfection might provide a useful platform to address multiple targets that are still considered undruggable in CF.

Congress abstracts

– Costabile G, Baldassi D, D’Angelo I et al. “In vitro evaluation of siRNA loaded hNPs for the treatment of cystic fibrosis” NIM Conference “The Future of Nanoscience”, Tutzig, Germany, September 4-6, 2018
– d’Angelo I, Costabile G, Durantie E, et al. “Inhalable hybrid lipid/polymer nanoparticles for pulmonary delivery of siRNA in cystic fibrosis” 11th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Granada, Spain, March 19-22, 2018