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

Pharmaceutics

Eckart Rühl¹  Iuliia Pilipenko²  Tatiana Tennikova²  Vladimir Sharoyko²  Viktor Korzhikov-Vlakh²  Monika Schäfer-Korting³  Christian Zoschke³  Nan Zhang³ 

[1] Institute of Chemistry and Biochemistry (Physical Chemistry), Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany;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;

关键词: chitosan;    cytotoxicity;    DNA;    heparin;    transfection;    pH-sensitive;   

DOI  :  10.3390/pharmaceutics11070317

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown