PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion

Xuan Jiang, Hui Dai, Chyan Ying Ke, Xiao Mo, Michael S. Torbenson, Zhiping Li, Hai Quan Mao

Research output: Contribution to journalArticle

Abstract

We have developed a new block copolymer gene carrier that comprises of a polyethylene glycol segment and a degradable cationic polyphosphoramidate (PPA) segment. This PEG-b-PPA copolymer carrier formed micelles upon condensation with plasmid DNA in aqueous solution. PEG-b-PPA/DNA micelles exhibited uniform and reduced particle size ranging from 80 to 100 nm and lowered surface charge, compared with complexes of DNA with the corresponding cationic PPA carrier. PEG-b-PPA/DNA micelles maintained similar transfection efficiency as PPA/DNA complexes, which was comparable to that of PEI/DNA complexes in HepG2 cells, but yielded about 16-fold lower transgene expression in primary rat hepatocytes than PPA/DNA complexes. Following bile duct infusion in Wistar rats, PEG-b-PPA/DNA micelles mediated 4-fold higher and more uniform gene expression in the liver than PPA/DNA complexes. Liver function tests and histopathological examination indicated that PEG-b-PPA/DNA micelles showed low toxicity and good biocompatibility in the liver. This study demonstrated the potential of PEG-b-PPA/DNA micelles as an efficient carrier for liver-targeted gene delivery.

Original languageEnglish (US)
Pages (from-to)297-304
Number of pages8
JournalJournal of Controlled Release
Volume122
Issue number3
DOIs
StatePublished - Oct 8 2007

Keywords

  • Block copolymer
  • Gene delivery
  • Intrabiliary infusion
  • Liver-targeted
  • Polymeric micelles
  • Polyphosphoramidate

ASJC Scopus subject areas

  • Pharmaceutical Science

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