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 language | English (US) |
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Pages (from-to) | 1723-1732 |
Number of pages | 10 |
Journal | Pharmaceutical Research |
Volume | 28 |
Issue number | 7 |
DOIs | |
State | Published - Jul 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)