Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles

Abstract Cystic fibrosis (CF) is characterized by an airway obstruction caused a thick mucus due to malfunctioning Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky restricts drugs in reaching target cells limiting the efficiency of treatments. development new approaches enhance drug delivery lungs represents CF treatment's main challenge. In this work, we report production and characterization hybrid core–shell nanoparticles (hNPs) comprising PLGA core dipalmitoylphosphatidylcholine (DPPC) shell engineered for inhalation. We loaded hNPs with 7-mer peptide nucleic acid (PNA) previously considered its ability modulate post-transcriptional regulation CFTR gene. also investigated vitro release kinetics their efficacy PNA across human epithelial barrier using ex vivo model based on primary nasal (HNEC) from patients. Confocal analyses transport assay demonstrated overcome cargo within cytoplasm, where it can exert biological function.