Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
Received 3 July 2012
Accepted for publication 7 September 2012
Published 23 November 2012 Volume 2012:7 Pages 5833—5845
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Julio C Fernandes,1 Xingping Qiu,2 Francoise M Winnik,2 Mohamed Benderdour,1 Xiaoling Zhang,3 Kerong Dai,3 Qin Shi1
1Orthopaedics Research Laboratory, Research Centre, Sacré-Coeur Hospital, 2Department of Physical Chemistry and Polymer Science, Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada; 3Orthopaedic Cellular and Molecular Biology Laboratories, Institute of Health Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Abstract: The low transfection efficiency of chitosan is one of its drawbacks as a gene delivery carrier. Low molecular weight chitosan may help to form small-sized polymer-DNA or small interfering RNA (siRNA) complexes. Folate conjugation may improve gene transfection efficiency because of the promoted uptake of folate receptor-bearing cells. In the present study, chitosan was conjugated with folate and investigated for its efficacy as a delivery vector for siRNA in vitro. We demonstrate that the molecular weight of chitosan has a major influence on its biological and physicochemical properties, and very low molecular weight chitosan (below 10 kDa) has difficulty in forming stable complexes with siRNA. In this study, chitosan 25 kDa and 50 kDa completely absorbed siRNA and formed nanoparticles (≤220 nm) at a chitosan to siRNA weight ratio of 50:1. The introduction of a folate ligand onto chitosan decreased nanoparticle toxicity. Compared with chitosan-siRNA, folate-chitosan-siRNA nanoparticles improved gene silencing transfection efficiency. Therefore, folate-chitosan shows potential as a viable candidate vector for safe and efficient siRNA delivery.
Keywords: nonviral vector, chitosan, gene delivery, folate-targeted, siRNA
© 2012 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.