PEGylation of 6-amino-6-deoxy-curdlan for efficient in vivo siRNA delivery

Carbohydr Polym. 2016 May 5:141:92-8. doi: 10.1016/j.carbpol.2015.12.077. Epub 2015 Dec 31.

Abstract

RNA interference (RNAi) is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies need to establish efficient delivery system that silences target genes with siRNA doses that is clinically feasible in humans. Here we report synthesis and in vivo study of a novel PEGylated curdlan-based nanoparticle, designated as 6AC-100PEG, obtained by conjugation of mPEG 2000 to 6-amino-6-deoxy-curdlan. The complex of siRNA/6AC-100PEG showed homogenous nanoparticles with an average diameter of 200nm. MTT assay indicated that 6AC-100PEG does not have apparent cytotoxicity. Systemic administration of a complex of siapoB/6AC-100PEG significantly reduced the level of apoB mRNA in mouse liver, indicating that 6AC-100PEG can efficiently deliver siRNA to mouse liver and induce RNAi. Administration of siRNA/6AC-100PEG to mouse did not elevate liver enzyme level in the serum, indicating that 6AC-100PEG nanoparticle is a promising in vivo siRNA delivery agent.

Keywords: Biodistribution; Curdlan; Nanoparticle; PEG; siRNA delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins B / blood
  • Apolipoproteins B / genetics
  • Hep G2 Cells
  • Humans
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanocapsules / adverse effects
  • Nanocapsules / chemistry*
  • Polyethylene Glycols / chemistry*
  • RNA, Small Interfering / administration & dosage*
  • Tissue Distribution
  • beta-Glucans / chemistry*

Substances

  • Apolipoproteins B
  • Nanocapsules
  • RNA, Small Interfering
  • beta-Glucans
  • Polyethylene Glycols
  • curdlan