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Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies

Authors Fernandes JC, Qiu X, Winnik FM, Benderdour M, Zhang X, Dai K, Shi Q

Received 3 July 2012

Accepted for publication 7 September 2012

Published 23 November 2012 Volume 2012:7 Pages 5833—5845

DOI https://doi.org/10.2147/IJN.S35567

Checked for plagiarism Yes

Review by Single-blind

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

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Other article by this author:

Linear polyethylenimine produced by partial acid hydrolysis of poly(2-ethyl-2-oxazoline) for DNA and siRNA delivery in vitro

Fernandes JC, Qiu X, Winnik FM, Benderdour M, Zhang X, Dai K, Shi Q

International Journal of Nanomedicine 2013, 8:4091-4102

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