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

Water-soluble substituted chitosan derivatives as technology platform for inhalation delivery of siRNA. Drug Deliv. 2018 Nov;25(1):644-653 Authors: Capel V, Vllasaliu D, Watts P, Clarke PA, Luxton D, Grabowska AM, Mantovani G, Stolnik S 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...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research