Development of a novel method for formulating stable siRNA-loaded lipid particles for In vivo use

Wu, Sherry Y., Putral, Lisa N., Liang, Mingtao, Chang, Hsin-I, Davies, Nigel M. and McMillan, Nigel A.J. (2009) Development of a novel method for formulating stable siRNA-loaded lipid particles for In vivo use. Pharmaceutical Research, 26 3: 512-522. doi:10.1007/s11095-008-9766-1


Author Wu, Sherry Y.
Putral, Lisa N.
Liang, Mingtao
Chang, Hsin-I
Davies, Nigel M.
McMillan, Nigel A.J.
Title Development of a novel method for formulating stable siRNA-loaded lipid particles for In vivo use
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
1573-904X
Publication date 2009-03-01
Year available 2008
Sub-type Article (original research)
DOI 10.1007/s11095-008-9766-1
Open Access Status Not Open Access
Volume 26
Issue 3
Start page 512
End page 522
Total pages 11
Place of publication The United States of America
Publisher Springer/plenum Publishers
Language eng
Subject C1
111204 Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
920102 Cancer and Related Disorders
Formatted abstract
Purpose
A simple yet novel method was developed to prepare stable PEGylated siRNA-loaded lipid particles which are suitable for in vivo use.

Methods
PEGylated siRNA-loaded lipid particles were formulated by hydration of a freeze-dried matrix. The effect of various formulation parameters on the size and homogeneity of resulting particles was studied. Particles prepared using this method were compared to those prepared using an established post-insertion procedure for the entrapment efficiency, stability, in vitro biological activity as well as in vivo biodistribution.

Results
Using this hydration method, a particle size of less than 200 nm can be obtained with high siRNA entrapment efficiency (>90%) and high gene-silencing efficiency. Following intravenous administration into mice, these particles achieved a similar degree of accumulation in subcutaneous tumours but displayed less liver uptake compared to the post-insertion formulations. Importantly, in contrast to post-insertion preparations, particles made by hydration method retained 100% of their gene-silencing efficiency after storage at room temperature for 1 month.

Conclusions
This paper describes a simple method of formulating PEGylated siRNA-loaded lipid particles. Given the ease of preparation, long term stability and favourable characteristics for in vivo delivery, our work represents an advance in lipid formulation of siRNA for in vivo use.
Keyword cancer
liposomes
PEGylation
siRNA
systemic gene delivery
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 29 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 30 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 01 Apr 2009, 21:17:16 EST by Kylie Hengst on behalf of UQ Diamantina Institute