TY - JOUR

T1 - pH-sensitive chitosan–heparin nanoparticles for effective delivery of genetic drugs into epithelial cells

AU - Pilipenko, Iuliia

AU - Korzhikov-Vlakh, Viktor

AU - Sharoyko, Vladimir

AU - Zhang, Nan

AU - Schäfer-Korting, Monika

AU - Rühl, Eckart

AU - Zoschke, Christian

AU - Tennikova, Tatiana

N1 - 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.

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - хитозан

KW - цитотоксичность

KW - ДНК

KW - Гепарин

KW - рН-чувствительность

KW - трансфекция

UR - http://www.scopus.com/inward/record.url?scp=85071359610&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics11070317

DO - 10.3390/pharmaceutics11070317

M3 - Article

AN - SCOPUS:85071359610

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 7

M1 - 317

ER -