Mucosal Delivery of RNAi Therapeutics - RNA Interference from Biology to Therapeutics - page 102

Table 5.1 Pulmonary delivery of siRNA
Formulation Route/animal Molecular target/model Effect (dosage) Ref./year

Naked siRNA
Naked Intranasal C57BL/6 mice PAI-1/bleomycin induced

pulmonary fi brosis model

Suppresion of PAI-1 resulted in prevention
of fibrosis (multiple doses, 2 mM in 50 m l)

[ 58 ] /2010

Naked Intranasal C57BL/6J mice HO-1/ischaemia reperfusion

injury

Administration of HO-1 siRNA increased
apoptosis in lung (1 × 2 mg/kg)

[ 59 ] /2004

Naked Intratracheal C3H/HeN mice KC and MIP-2/acute lung injury ~40% reduction of KC and MIP-2 mRNA

(1 × 75 m g)

[ 60 ] /2005

Naked Intratracheal C57BL/6 mice XCL-1/ M. tuberculosis 50% reduction in xcl1 mRNA levels and 40%

reduction in protein levels (1 × 5-15 m g)

[ 61 ] /2009

Naked Intratracheal C3H/HeN mice Fas and caspase-8/acute lung

injury

Reduction of Fas and caspase-8 mRNA
(1 × 75 m g)

[ 62 ] /2005

Naked/Mirus TKO Intranasal BALB/c mice Phosphoroprotein/RSV Several log reduction of viral titres (1 × 70 m g) [ 63 ] /2005

Naked Intranasal BALB/c mice Nucleocapsid mRNA /RSV 2.5-3 log reduction in RSV lung concentration

(single or multiple doses, 40-120 m g)

[ 76 ] /2009

Naked/Lipofectamine Intranasal BALB/c mice Ori and glycoprotein B/EHV-1 Antiviral effect observed 1 × 62.5 pmol) [ 65 ] /2009

Naked Intranasal rhesus macaque SARS Corona virus/replicase,

transcriptase and structural
proteins

Anti-SARS effect by prophylactic or therapeu-
tic regimens (1 × 30 m g)

[ 64 ] /2005

Naked Nasal spray human Nucleocapsid mRNA/RSV 38% reduction in experimentally infected

patients (150 mg/day for 4 days)

[ 14 ] /2010

Naked LNA modified I.V. C57BL/6-Yg mice EGFP/EGFP transgenic mice 55% reduction of EGFP (5 × 50 m g) [ 66 ] /2009

Polymers
Chitosan

Intranasal C57BL/6-Yg mice EGFP/EGFP transgenic mice ~40% reduction in EGFP expressing

bronchoepithelium cells (5 × 30 m g)

[ 7 ] /2006