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 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...

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Autores principales:	Marika Comegna, Gemma Conte, Andrea Patrizia Falanga, Maria Marzano, Gustavo Cernera, Antonella Miriam Di Lullo, Felice Amato, Nicola Borbone, Stefano D’Errico, Francesca Ungaro, Ivana d’Angelo, Giorgia Oliviero, Giuseppe Castaldo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c90d998c17c94a5e9958764703a866ce
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spelling	oai:doaj.org-article:c90d998c17c94a5e9958764703a866ce2021-12-02T17:05:46ZAssisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles10.1038/s41598-021-85549-z2045-2322https://doaj.org/article/c90d998c17c94a5e9958764703a866ce2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85549-zhttps://doaj.org/toc/2045-2322Abstract 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 production 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 exert its biological function.Marika ComegnaGemma ConteAndrea Patrizia FalangaMaria MarzanoGustavo CerneraAntonella Miriam Di LulloFelice AmatoNicola BorboneStefano D’ErricoFrancesca UngaroIvana d’AngeloGiorgia OlivieroGiuseppe CastaldoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marika Comegna Gemma Conte Andrea Patrizia Falanga Maria Marzano Gustavo Cernera Antonella Miriam Di Lullo Felice Amato Nicola Borbone Stefano D’Errico Francesca Ungaro Ivana d’Angelo Giorgia Oliviero Giuseppe Castaldo Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
description	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 production 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 exert its biological function.
format	article
author	Marika Comegna Gemma Conte Andrea Patrizia Falanga Maria Marzano Gustavo Cernera Antonella Miriam Di Lullo Felice Amato Nicola Borbone Stefano D’Errico Francesca Ungaro Ivana d’Angelo Giorgia Oliviero Giuseppe Castaldo
author_facet	Marika Comegna Gemma Conte Andrea Patrizia Falanga Maria Marzano Gustavo Cernera Antonella Miriam Di Lullo Felice Amato Nicola Borbone Stefano D’Errico Francesca Ungaro Ivana d’Angelo Giorgia Oliviero Giuseppe Castaldo
author_sort	Marika Comegna
title	Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
title_short	Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
title_full	Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
title_fullStr	Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
title_full_unstemmed	Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
title_sort	assisting pna transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c90d998c17c94a5e9958764703a866ce
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Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles

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