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Open AccessFeature PaperArticle

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

Institute of Chemistry, Saint Petersburg State University, Peterhoff, Universitetskii pr. 26, 198504 St. Petersburg, Russia
Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany
Institute of Chemistry and Biochemistry (Physical Chemistry), Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(7), 317;
Received: 29 May 2019 / Revised: 2 July 2019 / Accepted: 3 July 2019 / Published: 5 July 2019
(This article belongs to the Special Issue Drug Delivery across Biological Barriers)
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. View Full-Text
Keywords: chitosan; cytotoxicity; DNA; heparin; transfection; pH-sensitive chitosan; cytotoxicity; DNA; heparin; transfection; pH-sensitive
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Pilipenko, I.; Korzhikov-Vlakh, V.; Sharoyko, V.; Zhang, N.; Schäfer-Korting, M.; Rühl, E.; Zoschke, C.; Tennikova, T. pH-Sensitive Chitosan–Heparin Nanoparticles for Effective Delivery of Genetic Drugs into Epithelial Cells. Pharmaceutics 2019, 11, 317.

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