Skip to main content

Research Repository

See what's under the surface

Advanced Search

Water-soluble substituted chitosan derivatives as technology platform for inhalation delivery of siRNA

Capel, Victoria; Vllasaliu, Driton; Watts, Peter; Clarke, Philip A.; Luxton, Dominic; Grabowska, Anna M.; Mantovani, Giuseppe; Stolnik, Snow

Authors

Victoria Capel

Driton Vllasaliu

Peter Watts

Philip A. Clarke

Dominic Luxton

Anna M. Grabowska

Giuseppe Mantovani giuseppe.mantovani@nottingham.ac.uk

Snow Stolnik snow.stolnik@nottingham.ac.uk



Abstract

Despite research efforts full potential of siRNA-based therapeutics has not yet been fully realized due to a need for suitable, effective delivery formulations. Here, we examine a potential of a new class of water-soluble chitosans as siRNA platform for pulmonary delivery. The system is based on piperazine-substituted chitosans, a material designed to integrate established, safe application of chitosan for mucosal administration with novel properties: the piperazine-substituted chitosans are freely water-soluble at physiological pH, possess low cytotoxicity (no significant reduction in cell viability up to 0.1 mg/ml), and provide efficient incorporation of siRNA into sub-300 nm colloidal complexes (at relatively low polymer/siRNA ratio of 5:1). In vitro, the complexes achieved silencing of a model gene at a level of 40–80%, when tested in a panel of lung epithelial cells. Considering the formulation ‘developability’, there were no significant changes in the complexes’ size and integrity on aerosolisation by microsprayer (PenCenturyTM) device. Following intratracheal aerolisation, the complexes deposited throughout the lung, although relatively inhomogeneously, as judged from IVIS imaging of the isolated mouse lung (visualizing DY647-siRNA). In vivo data illustrate absence of adverse effects on repeated administration of complexes and significant tumor reduction in atopical lung cancer model in mice. Altogether, the data illustrates potential of substituted chitosan derivatives to be utilized as a safe system for inhalation delivery of siRNA.

Journal Article Type Article
Journal Drug Delivery
Print ISSN 1071-7544
Electronic ISSN 1521-0464
Publisher Taylor & Francis
Peer Reviewed Peer Reviewed
Volume 25
Issue 1
APA6 Citation Capel, V., Vllasaliu, D., Watts, P., Clarke, P. A., Luxton, D., Grabowska, A. M., …Stolnik, S. (in press). Water-soluble substituted chitosan derivatives as technology platform for inhalation delivery of siRNA. Drug Delivery, 25(1), doi:10.1080/10717544.2018.1440668
DOI https://doi.org/10.1080/10717544.2018.1440668
Keywords Chitosan, siRNA delivery, siRNA complex, lung inhalation, IVIS imaging
Publisher URL https://www.tandfonline.com/doi/full/10.1080/10717544.2018.1440668
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

Files

Water soluble substituted chitosan derivatives as technology platform for inhalation delivery of siRNA.pdf (1.7 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





You might also like



Downloadable Citations

;