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pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells

Chitosan has been extensively studied as a genetic drug delivery platform. However, its efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding strength of cargo with chitosan, we proposed including heparin as a competing polyanion in the polyplexes. We developed ch...

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Autores principales: Pilipenko, Iuliia, Korzhikov-Vlakh, Viktor, Sharoyko, Vladimir, Zhang, Nan, Schäfer-Korting, Monika, Rühl, Eckart, Zoschke, Christian, Tennikova, Tatiana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680926/
https://www.ncbi.nlm.nih.gov/pubmed/31284414
http://dx.doi.org/10.3390/pharmaceutics11070317
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author Pilipenko, Iuliia
Korzhikov-Vlakh, Viktor
Sharoyko, Vladimir
Zhang, Nan
Schäfer-Korting, Monika
Rühl, Eckart
Zoschke, Christian
Tennikova, Tatiana
author_facet Pilipenko, Iuliia
Korzhikov-Vlakh, Viktor
Sharoyko, Vladimir
Zhang, Nan
Schäfer-Korting, Monika
Rühl, Eckart
Zoschke, Christian
Tennikova, Tatiana
author_sort Pilipenko, Iuliia
collection PubMed
description Chitosan has been extensively studied as a genetic drug delivery platform. However, its efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding strength of cargo with chitosan, we proposed including heparin as a competing polyanion in the polyplexes. We developed chitosan–heparin nanoparticles by a one-step process for the local delivery of oligonucleotides. The size of the polyplexes was dependent on the mass ratio of polycation to polyanion. The mechanism of oligonucleotide release was pH-dependent and associated with polyplex swelling and collapse of the polysaccharide network. Inclusion of heparin enhanced the oligonucleotide release from the chitosan-based polyplexes. Furthermore, heparin reduced the toxicity of polyplexes in the cultured cells. The cell uptake of chitosan–heparin polyplexes was equal to that of chitosan polyplexes, but heparin increased the transfection efficiency of the polyplexes two-fold. The application of chitosan–heparin small interfering RNA (siRNA) targeted to vascular endothelial growth factor (VEGF) silencing of ARPE-19 cells was 25% higher. Overall, chitosan–heparin polyplexes showed a significant improvement of gene release inside the cells, transfection, and gene silencing efficiency in vitro, suggesting that this fundamental strategy can further improve the transfection efficiency with application of non-viral vectors.
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spelling pubmed-66809262019-08-09 pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells Pilipenko, Iuliia Korzhikov-Vlakh, Viktor Sharoyko, Vladimir Zhang, Nan Schäfer-Korting, Monika Rühl, Eckart Zoschke, Christian Tennikova, Tatiana Pharmaceutics Article Chitosan has been extensively studied as a genetic drug delivery platform. However, its efficiency is limited by the strength of DNA and RNA binding. Expecting a reduced binding strength of cargo with chitosan, we proposed including heparin as a competing polyanion in the polyplexes. We developed chitosan–heparin nanoparticles by a one-step process for the local delivery of oligonucleotides. The size of the polyplexes was dependent on the mass ratio of polycation to polyanion. The mechanism of oligonucleotide release was pH-dependent and associated with polyplex swelling and collapse of the polysaccharide network. Inclusion of heparin enhanced the oligonucleotide release from the chitosan-based polyplexes. Furthermore, heparin reduced the toxicity of polyplexes in the cultured cells. The cell uptake of chitosan–heparin polyplexes was equal to that of chitosan polyplexes, but heparin increased the transfection efficiency of the polyplexes two-fold. The application of chitosan–heparin small interfering RNA (siRNA) targeted to vascular endothelial growth factor (VEGF) silencing of ARPE-19 cells was 25% higher. Overall, chitosan–heparin polyplexes showed a significant improvement of gene release inside the cells, transfection, and gene silencing efficiency in vitro, suggesting that this fundamental strategy can further improve the transfection efficiency with application of non-viral vectors. MDPI 2019-07-05 /pmc/articles/PMC6680926/ /pubmed/31284414 http://dx.doi.org/10.3390/pharmaceutics11070317 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pilipenko, Iuliia
Korzhikov-Vlakh, Viktor
Sharoyko, Vladimir
Zhang, Nan
Schäfer-Korting, Monika
Rühl, Eckart
Zoschke, Christian
Tennikova, Tatiana
pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells
title pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells
title_full pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells
title_fullStr pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells
title_full_unstemmed pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells
title_short pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells
title_sort ph-sensitive chitosan–heparin nanoparticles for effective delivery of genetic drugs into epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680926/
https://www.ncbi.nlm.nih.gov/pubmed/31284414
http://dx.doi.org/10.3390/pharmaceutics11070317
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