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

Drug Delivery
Victoria CapelSnjezana Stolnik

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 (PenCentury™) device. Following intratracheal aerolisation, the complexes deposited throughout the lung, although relatively inhomogeneously, as judged from IVIS imaging of the isolated mouse lung (visualizing D...Continue Reading

References

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Jun 29, 2016·Biochemical and Biophysical Research Communications·Victoria CapelSnow Stolnik

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Citations

Jan 17, 2019·Mini Reviews in Medicinal Chemistry·Paulina PaulWitold Sujka
Nov 7, 2019·Drug Development Research·Kamal DuaDinesh Kumar Chellappan
Oct 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·T J ThomasC K S Pillai
Nov 5, 2019·Journal of Controlled Release : Official Journal of the Controlled Release Society·A Nieto-OrellanaS Stolnik
Nov 13, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ling DingDavid Oupický
Aug 11, 2019·Advanced Drug Delivery Reviews·Joydeb MajumderTamara Minko

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Methods Mentioned

BETA
electrophoresis
dynamic light scattering
xenograft
transfection
xenografts

Software Mentioned

RT Sizer
GraphPad Prism
Living Image

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