Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells

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http://hdl.handle.net/10138/313285

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Osipova , O , Sharoyko , V , Zashikhina , N , Zakharova , N , Tennikova , T , Urtti , A & Korzhikova-Vlakh , E 2020 , ' Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells ' , Pharmaceutics , vol. 12 , no. 1 , 39 . https://doi.org/10.3390/pharmaceutics12010039

Title: Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells
Author: Osipova, Olga; Sharoyko, Vladimir; Zashikhina, Natalia; Zakharova, Natalya; Tennikova, Tatiana; Urtti, Arto; Korzhikova-Vlakh, Evgenia
Contributor: University of Helsinki, Drug Research Program
Date: 2020-01
Language: eng
Number of pages: 17
Belongs to series: Pharmaceutics
ISSN: 1999-4923
URI: http://hdl.handle.net/10138/313285
Abstract: Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and (HNMR)-H-1 spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.
Subject: amphiphilic polypeptides
self-assembly
nanoparticles
siRNA delivery
VEGF
gene silencing
OCULAR ANGIOGENESIS
NANOPARTICLES
THERAPIES
INHIBITION
PACLITAXEL
317 Pharmacy
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