In vitro studies demonstrated that the developed siRNA-loaded hybrid nanoparticles (hNPs) may penetrate lung extracellular barriers, as CF mucus, allowing a significantly higher uptake in human bronchial epithelial cells as compared to both free siRNA and siRNA/lipofectamine complexes. As a result, significant nuclear factor-kB(NF-kB) downregulation up to 72h was observed in human bronchial epithelial cells treated with optimised siRNA-loaded hNPs. Moreover, preliminary efficacy studies upon intratracheal administration in LPS-challenged rats highlighted the potential of the developed siRNA-loaded to downregulate NF-kB also in vivo. The perspective is that optimized nanoparticles could move to further in vivo preclinical studies, which are essential to translate the technology under development from labs to the clinics. The development of a siRNA delivery system already engineered for in vivo inhalation and transfection might shorten the time to translation to patients, providing a therapeutic platform to address multiple targets that are still considered “undruggable” in CF.

Congress abstracts

• Ungaro F, Overcoming lung barriers to siRNA delivery in cystic fibrosis through tailored lipid/polymer hybrid nanoparticles, 11th Annual RNA Therapeutics Conference Focus Day – Oligonucleotide Delivery Systems, 18th February 2020, London, UK
• Baldassi D, Costabile G, Conte G et al. In vitro evaluation of siRNA loaded hNPs for the treatment of cystic fibrosis, International Conference on Nanomedicine and Nanobiotechnology 2019 (ICONAN 2019), October 16th – 18th, 2019, Munich, Germany
• D’Angelo I, Conte G, Costabile G et al. Enabling pulmonary delivery of siRNA in cystic fibrosis lung inflammation through hybrid lipid/polymer nanoparticles, International Society for Aerosol in Medicine e.V., 22nd ISAM Congress, Montreaux, Switzerland, May 25-29, 2019
• D’Angelo I, Conte G, Costabile G et al. Tailored hybrid lipid/polymer nanoparticles for pulmonary delivery of siRNA in cystic fibrosis, IV International Caparica Symposium on Nanoparticles/Nanomaterials and Applications 2020 (ISN2A2020), January 20th-23rd, 2020, Caparica, Portugal
• Costabile G, Buroni S, Provenzano R et al. Elongated mucus-penetrating nanocrystals for lung delivery of a new anti-Burkholderia agent in cystic fibrosis, International Society for Aerosol in Medicine e.V., 22nd ISAM Congress, Montreaux, Switzerland, May 25-29, 2019
• Costabile G, Provenzano R, Mitidieri E et al. Repurposing Gallium for local treatment of P. aeruginosa lung infections through sustained-release dry powders for inhalation, International Society for Aerosol in Medicine e.V.”, 22nd ISAM Congress, Montreaux, Switzerland, May 25-29, 2019
• D’Angelo I, Casciaro B, Zhang X et al. Biodegradable nanoparticles for prolonged therapeutic efficacy of antimicrobial peptides against Pseudomonas aeruginosa lung infections, International Society for Aerosol in Medicine e.V.”, 22nd ISAM Congress, Montreaux, Switzerland, May 25-29, 2019