Mucosal Delivery of RNAi Therapeutics - RNA Interference from Biology to Therapeutics - page 111

Table 5.2 Oral, rectal and intravaginal delivery of siRNA
Formulation Route/animal Molecular target/model Effect (dosage) Ref./year

b -1, 3- D-glucan shells Oral C57BL6/J mice TNF-a, Map4k4 Untreated

animals and LPS lethality
test

Knock-down of target genes. Protection from
LPS-induced lethality (~0.4 mg/dose for 8
consecutive days)

[ 88 ] /2009

Thioketal nanoparticles Oral C57BL/6 mice TNF-a DSS-induced colitis TNF-a Knock-down. Protection from colitis

(~46 mg/dose or 4.6 mg/dose for 5 consecutive
days)

[ 89 ] /2010

NiMOS Oral Balb/c mice TNF- a DSS-induced colitis TNF-a knock-down. Milder colitis symptoms

(~24 mg/dose for 3 alternated days)

[ 90 ] /2011

Stabilised unilamellar
vesicles b 7 integrin-
targeted

Intravenous C57BL/
6 mice

CyD1 DSS-induced colitis CyD1 knock-down. Alleviated colitis symptoms

(~50 mg/dose for 4 alternated days)

[ 91 ] /2008

Lipoplex (Lipofectamine) Rectal C57BL/6 mice TNF-a DSS-induced colitis TNF-a knock-down in descending colon. Mild

or moderate inflammation (~53 mg/dose for 2
alternated days)

[ 92 ] /2006

Lipoplex (DOTAP) chemical
modi fi ed siRNA

Rectal Swiss-Webster mice None detection of fluorescent-

labelled siRNA

Uptake in spleen, colon and bone marrow
(single dose of ~20 m g)

[ 93 ] /2007

Lipoplex (Oligofectamine) Intravaginal Balb/c mice UL27 &UL29 viral genes

HSV-2 lethal challenge

Protection from HSV-2 lethal infection (two doses
of ~7 m g)

[ 94 ] /2006

Naked (cholesterol
conjugated chemical
stabilised siRNA)

Intravaginal Balb/c mice Viral (UL29) & host (nectin-1)

genes HSV-2 lethal
challenge

Protection from HSV-2 lethal infection
(~27 mg/dose for 2 consecutive days)

[ 95 ] /2009

PLGA nanoparticles Intravaginal FVB Cg-Tg

(GFPU)5 Nagy mice

GFP transgenic GFP mice GFP gene silencing throughout reproductive tract

(single dose of ~7 m g)

[ 96 ] /2009

Lipoplex (Lipofectamine) Intravaginal C57BL/6 mice Lamin A/C, CCR5 Knock-down of target genes (single dose of ~53 m g ) [ 92 ] /2006

PEGylated Lipoplexes
entrapped in alginate
scaffold

Intravaginal C57BL/6 and
K14E7 mice

Lamin A/C Lamin A/C knock-down (two doses of ~8 m g) [ 97 ] /2011

Naked (CD4 aptamer-
siRNA chimera)

Intravaginal NOD/SCID-BLT
& NSG-BLT mice

Viral ( gag,vif) and host ( CCR5 )
genes Humanised mice

Protection against HIV vaginal transmission
(~4 mg in complex dosing regimen)

[ 98 ] /2011