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

Julio C Fernandes,1 Xingping Qiu,2 Francoise M Winnik,2 Mohamed Benderdour,1 Xiaoling Zhang,3 Kerong Dai,3 Qin Shi11Orthopaedics Research Laboratory, Research Centre, Sacr&eacute;-Coeur Hospital, 2Department of Physical Chemistry and Polymer Science, Faculty of Pharmacy, University of Montre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shi Q, Dai K, Zhang X, Benderdour M, Winnik FM, Qiu X, Fernandes JC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/26c754d972ea4a6aa926f1ee7239e70a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:26c754d972ea4a6aa926f1ee7239e70a
record_format	dspace
spelling	oai:doaj.org-article:26c754d972ea4a6aa926f1ee7239e70a2021-12-02T07:37:35ZLow molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies1176-91141178-2013https://doaj.org/article/26c754d972ea4a6aa926f1ee7239e70a2012-11-01T00:00:00Zhttp://www.dovepress.com/low-molecular-weight-chitosan-conjugated-with-folate-for-sirna-deliver-a11593https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Julio C Fernandes,1 Xingping Qiu,2 Francoise M Winnik,2 Mohamed Benderdour,1 Xiaoling Zhang,3 Kerong Dai,3 Qin Shi11Orthopaedics Research Laboratory, Research Centre, Sacr&eacute;-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, ChinaAbstract: 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 (&le;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, siRNAShi QDai KZhang XBenderdour MWinnik FMQiu XFernandes JCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5833-5845 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shi Q Dai K Zhang X Benderdour M Winnik FM Qiu X Fernandes JC Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
description	Julio C Fernandes,1 Xingping Qiu,2 Francoise M Winnik,2 Mohamed Benderdour,1 Xiaoling Zhang,3 Kerong Dai,3 Qin Shi11Orthopaedics Research Laboratory, Research Centre, Sacr&eacute;-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, ChinaAbstract: 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 (&le;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
format	article
author	Shi Q Dai K Zhang X Benderdour M Winnik FM Qiu X Fernandes JC
author_facet	Shi Q Dai K Zhang X Benderdour M Winnik FM Qiu X Fernandes JC
author_sort	Shi Q
title	Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
title_short	Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
title_full	Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
title_fullStr	Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
title_full_unstemmed	Low molecular weight chitosan conjugated with folate for siRNA delivery in vitro: optimization studies
title_sort	low molecular weight chitosan conjugated with folate for sirna delivery in vitro: optimization studies
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/26c754d972ea4a6aa926f1ee7239e70a
work_keys_str_mv	AT shiq lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies AT daik lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies AT zhangx lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies AT benderdourm lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies AT winnikfm lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies AT qiux lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies AT fernandesjc lowmolecularweightchitosanconjugatedwithfolateforsirnadeliveryinvitrooptimizationstudies
_version_	1718399270325846016

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

Ejemplares similares