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Development of purified glycogen derivatives as siRNA nanovectors

Authors :
Francesco Leonetti
Nunzio Denora
Valentino Laquintana
Angela Lopedota
Massimo Franco
Loreto Gesualdo
Annalisa Cutrignelli
Juliette Vergnaud
Antonio Lopalco
Mauro Fiume
Giuseppe Francesco Racaniello
Elias Fattal
Paola Pontrelli
Source :
International Journal of Pharmaceutics. 608:121128
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Purified Glycogen (PG) is a highly hyper branched carbohydrate, characterized by high water solubility and very moderate increase in viscosity. The dendrimeric structure of PG, appropriately functionalized, makes it an alternative to current synthetic gene delivery agents. The present study explores the preparation of purified glycogen polycationic derivatives (PGPDs), developed and characterized starting from a single step reaction between PG and N,N-dialkylamino alkyl halides. Subsequently PGPDs were used for the complexation of a model siRNA nucleic acid, a transfection reagent siRNA and a fluorescein-labelled dsRNA oligomer. PGPDs-siRNA complexes were fully characterized by agarose gel electrophoresis and their efficacy was assessed by both confocal microscopy and transfection assays on breast and renal cancer cells. Results proved that PGPDs-siRNA complexes were efficient and not cytotoxic, maintaining their spherical and dendrimeric structure and, particularly, were able to effectively transfect the target cells by releasing the siRNA.

Details

ISSN :
03785173
Volume :
608
Database :
OpenAIRE
Journal :
International Journal of Pharmaceutics
Accession number :
edsair.doi.dedup.....c0511ce691031db1e88cb6a92e612c60