Acta Pharmaceutica Sinica B

Acta Pharmaceutica Sinica B

Volume 12, Issue 2, February 2022, Pages 600-620
Acta Pharmaceutica Sinica B

REVIEW
Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

https://doi.org/10.1016/j.apsb.2021.08.009Get rights and content
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Abstract

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

Graphical abstract

The pulmonary administration of siRNA in an appropriate delivery vector seems promising to treat undruggable lung diseases such as acute lung injury/acute respiratory distress syndrome ALI/ARDS.

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KEY WORDS

Pulmonary administration
Drug delivery
Nanoparticles
siRNA
Cellular uptake
Endosomal escape
Inflammatory diseases
ALI/ARDS

Abbreviations

AAV
adeno-associated virus
Ago-2
argonaute 2
ALI/ARDS
acute lung injury/acute respiratory distress syndrome
AM
alveolar macrophage
ATI
alveolar cell type I
ATII
alveolar cell type II
AV
adenovirus
CFDA
China Food and Drug Administration
COPD
chronic obstructive pulmonary disease
CPP
cell-penetrating peptide
CS
cigarette smoke
CXCR4
C–X–C motif chemokine receptor type 4
DPI
dry powder inhaler
DAMPs
danger-associated molecular patterns
DC-Chol
3β-(N-(N′,N′-dimethylethylenediamine)-carbamoyl) cholesterol
DODAP
1,2-dioleyl-3-dimethylammonium-propane
DODMA
1,2-dioleyloxy-N,N-dimethyl-3-aminopropane
DDAB
dimethyldioctadecylammonium bromide
DOGS
dioctadecyl amido glycin spermine
DOPC
1,2-dioleoyl-sn-glycero-3-phosphocholine
DOPE
1,2-dioleoyl-l-α-glycero-3-phosphatidylethanolamine
DOSPA
2,3-dioleyloxy-N-[2-(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium
DOTAP
1,2-dioleoyl-3-trimethylammonium-propane
DOTMA
N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium
DPPC
1,2-dipalmitoyl-sn-glycero-3-phosphocholine
dsDNA
double-stranded DNA
dsRNA
double-stranded RNA
EC
endothelial cell
eggPG
l-α-phosphatidylglycerol
EpiC
epithelial cell
EPC
egg phosphatidylcholine
EXOs
exosomes
FDA
US Food and Drug Administration
HALI
hyperoxic acute lung injury
Hem-CLP
hemorrhagic shock followed by cecal ligation and puncture septic challenge
HMGB1
high-mobility group box 1
HMVEC
human primary microvascular endothelial cell
HNPs
hybrid nanoparticles
ICAM-1
intercellular adhesion molecule-1
IFN
interferons
LPS
lipopolysaccharides
MEND
multifunctional envelope-type nano device
MIF
macrophage migration inhibitory factor
miRNA
microRNA
mRNA
messenger RNA
Myd88
myeloid differentiation primary response 88
N/P ratio
nitrogen /phosphate ratio
NETs
neutrophil extracellular traps
NF-κB
nuclear factor kappa B
NPs
nanoparticles
PAI-1
plasminogen activator inhibitor-1
PAMAM
polyamidoamine
PAMPs
pathogen-associated molecular patterns
PD-L1
programmed death ligand-1
PDGFRα
platelet-derived growth factor receptor-α
pDNA
plasmid DNA
PEEP
positive end-expiratory pressure
PEG
polyethylene glycol
PEI
polyethyleneimine
PF
pulmonary fibrosis
PFC
perfluorocarbon
PLGA
poly(d,l-lactic-co-glycolic acid)
PMs
polymeric micelles
PRR
pattern recognition receptor
PS
pulmonary surfactant
RIP2
receptor-interacting protein 2
RISC
RNA-induced silencing complex
RNAi
RNA interference
ROS
reactive oxygen species
shRNA
short RNA
siRNA
small interfering RNA
SLN
solid lipid nanoparticle
SNALP
stable nucleic acid lipid particle
TGF-β
transforming growth factor-β
TLR
Toll-like receptor
TNF-α
tumor necrosis factor-α
VALI
ventilator-associated lung injury
VILI
ventilator-induced lung injury

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Peer review under responsibility of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.

© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.