Sono state prodotte e sperimentate nanoparticelle ibride (combinazione di polimeri biodegradabili e fosfolipidi endogeni) contenenti un siRNA (short interfering RNA, corto frammento di RNA) in grado di inibire NF-kB, fondamentale molecola proinfiammatoria: esse hanno dimostrato la capacità di incapsulare efficacemente il siRNA e rilasciarlo per tempo prolungato in modelli cellulari. Gli studi proseguono con il progetto FFC#25/2018, in cui alcune formulazioni aerosolizzabili delle nanoparticelle prodotte saranno saggiate in un nuovo modello murino di infiammazione polmonare. Saranno condotte inoltre prove su muco da pazienti FC e su modelli complessi di epitelio polmonare. La prospettiva è di ottenere importanti avanzamenti nel campo delle nanotecnologie, un settore in forte sviluppo e potenzialità in campo terapeutico.
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.
– 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
