Enhanced stability and knockdown efficiency of poly(ethylene glycol)-b-polyphosphoramidate/siRNA micellar nanoparticles by Co-condensation with sodium triphosphate

Masataka Nakanishi, Rajesh Patil, Yong Ren, Rishab Shyam, Philip Wong, Hai Quan Mao

Research output: Contribution to journalArticle

Abstract

Purpose: Polyelectrolyte complex nanoparticles are a promising vehicle for siRNA delivery but suffer from low stability under physiological conditions. An effective stabilization method is essential for the success of polycationic nanoparticle-mediated siRNA delivery. In this study, sodium triphosphate (TPP), an ionic crosslinking agent, is used to stabilize siRNA-containing nanoparticles by co-condensation. Methods: siRNA and TPP were co-encapsulated into a block copolymer, poly(ethylene glycol)-b-polyphosphoramidate (PEG-b-PPA), to form ternary nanoparticles. Physicochemical characterization was performed by dynamic light scattering and gel electrophoresis. Gene silencing efficiency in cell lines was assessed by dual luciferase assay system. Results: The PEG-b-PPA/siRNA/TPP ternary nanoparticles exhibited high uniformity with smaller size (80-100 nm) compared with PEG-b-PPA/siRNA nanoparticles and showed increased stability in physiological ionic strength and serum-containing medium, due to the stabilization effect from ionic crosslinks between negatively charged TPP and cationic PPA segment. Transfection and gene silencing efficiency of the TPP-crosslinked nanoparticles were markedly improved over PEG-b-PPA/siRNA complexes in serum-containing medium. No significant difference in cell viability was observed between nanoparticles prepared with and without TPP co-condensation. Conclusions: These results demonstrated the effectiveness of TPP co-condensation in compacting polycation/siRNA nanoparticles, improving nanoparticle stability and enhancing the transfection and knockdown efficiency in serum-containing medium.

Original languageEnglish (US)
Pages (from-to)1723-1732
Number of pages10
JournalPharmaceutical Research
Volume28
Issue number7
DOIs
StatePublished - Jul 1 2011

Keywords

  • block copolymer gene carrier
  • siRNA
  • sodium triphosphate
  • stabilization
  • ternary nanoparticles

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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