Synthesis of cationic quaternized pullulan derivatives for miRNA delivery.

Int J Pharm

INSERM, U1148, Laboratory for Vascular Translational Science, X. Bichat Hospital, 46 rue Henri Huchard, 75018, Paris, France. Electronic address:

Published: March 2020

AI Article Synopsis

  • Pullulan is a biodegradable and non-toxic natural polysaccharide that can be modified to create cationic derivatives for biomedical use.
  • Researchers added quaternized ammonium groups to pullulan, enabling it to form stable complexes with microRNAs (miRNAs) through electrostatic interactions.
  • The results showed that these pullulan-miRNA polyplexes are safe for human cells and effectively promote miRNA delivery, highlighting their potential as a new method for gene delivery.

Article Abstract

Pullulan is a natural polysaccharide of potential interest for biomedical applications due to its non-toxic, non-immunogenic and biodegradable properties. The aim of this work was to synthesize cationic pullulan derivatives able to form complexes with microRNAs (miRNAs) driven by electrostatic interaction (polyplexes). Quaternized ammonium groups were linked to pullulan backbone by adding the reactive glycidyltrimethylammonium chloride (GTMAC). The presence of these cationic groups within the pullulan was confirmed by elemental analysis, Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (H NMR). The alkylated pullulan was able to interact with miRNA and form stable polyplexes that were characterized regarding size, zeta potential and morphology. The presence of miRNA was confirmed by agarose gel electrophoresis and UV spectrophotometry. In vitro tests on human umbilical vein endothelial cells did not show any cytotoxicity after 1 day of incubation with nanosized polyplexes up to 200 µg/mL. QA-pullulan was able to promote miRNA delivery inside cells as demonstrated by fluorescence microscopy images of labelled miRNA. In conclusion, the formation of polyplexes using cationic derivatives of pullulan with miRNA provided an easy and versatile method for polysaccharide nanoparticle production in aqueous media and could be a new promising platform for gene delivery.

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http://dx.doi.org/10.1016/j.ijpharm.2020.119041DOI Listing

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