1. Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
- Author
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Stefano D'Errico, Giuseppe Castaldo, Andrea Patrizia Falanga, Felice Amato, Marika Comegna, Antonella Miriam Di Lullo, Gustavo Cernera, Giorgia Oliviero, Nicola Borbone, Maria Marzano, Gemma Conte, Francesca Ungaro, Ivana d'Angelo, Comegna, Marika, Conte, Gemma, Falanga, Andrea Patrizia, Marzano, Maria, Cernera, Gustavo, Di Lullo, Antonella Miriam, Amato, Felice, Borbone, Nicola, D'Errico, Stefano, Ungaro, Francesca, D'Angelo, Ivana, Oliviero, Giorgia, Castaldo, Giuseppe, Comegna, M., Conte, G., Falanga, A. P., Marzano, M., Cernera, G., Di Lullo, A. M., Amato, F., Borbone, N., D'Errico, S., Ungaro, F., D'Angelo, I., Oliviero, G., and Castaldo, G.
- Subjects
Peptide Nucleic Acids ,Cystic Fibrosis ,1,2-Dipalmitoylphosphatidylcholine ,Science ,Cystic Fibrosis Transmembrane Conductance Regulator ,Diseases ,Cystic fibrosis ,Article ,chemistry.chemical_compound ,Drug Delivery Systems ,Nanoparticle ,Polylactic Acid-Polyglycolic Acid Copolymer ,medicine ,Humans ,Cystic Fibrosi ,Lung ,Multidisciplinary ,Molecular medicine ,Peptide nucleic acid ,biology ,Peptide Nucleic Acid ,respiratory system ,medicine.disease ,Mucus ,In vitro ,Cystic fibrosis transmembrane conductance regulator ,Cell biology ,Airway Obstruction ,Chemistry ,Nasal Mucosa ,PLGA ,chemistry ,Mucu ,Drug delivery ,biology.protein ,Nanoparticles ,Medicine ,CFTR gene, cystic fibrosis, PNA delivery, hybrid lipid-polymer nanoparticles ,Drug Delivery System ,Ex vivo ,Biotechnology ,Human - Abstract
Cystic Fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge. In this work, we report the synthesis and characterization of hybrid core-shell nanoparticles (hNPs) comprising a PLGA core and a dipalmitoylphosphatidylcholine (DPPC) shell engineered for inhalation. We loaded hNPs with a 7-mer peptide nucleic acid (PNA) previously considered for its ability to modulate the post-transcriptional regulation of the CFTR gene. We also investigated the in vitro release kinetics of hNPs and their efficacy in PNA delivery across the human epithelial airway barrier using an ex vivo model based on human primary nasal epithelial cells (HNEC) from CF patients. Confocal analyses and hNPs transport assay demonstrated the ability of hNPs to overcome the mucus barrier and release their PNA cargo within the cytoplasm, where it can perform its biological function.
- Published
- 2021