Biomedical Engineering Reference
In-Depth Information
Table 3.2 Optimized Hydrodynamic Delivery Procedures
Target Organ
Delivery Place
Testing Animal
Needle Gauge
Reference
Kidney
Renal vein
Rat
24
[33]
�iver
Tail vein
Mice
27
[88]
�iver
Tail vein
Rat
22
[33]
Muscle
Iliac artery
Mice
25
[98]
Muscle
Saphenous vein
Rat
-
[96]
Muscle
Saphenous vein
Dog
20
[96]
Muscle
Saphenous vein
Mouse
-
[96]
Muscle
Saphenous vein
Monkey
22
[96]
overview of some of the optimized hydrodynamic delivery procedures. To deliver the
DNA solution by intravenous route, needles with different gauge have been used, such
as 27G for tail vein injection in mice [69] and 22G needle for rat [87] . Based on injec-
tion speed, injection volume, and the type of blood vessels to be injected, needles with
different gauges are used, and the transfection efficiency mainly depends on the force
generated during hydrodynamic gene delivery. However, hydrodynamic delivery at a
brisk delivery rate or excess of injection volume can cause tissue damage and the death
of the animal [79] . Saline [68] , Ringers solution [80-85,88] , and phosphate-buffered
saline [86,87,89-94] are the most commonly used vehicles for hydrodynamic gene
delivery. Based on the application, the dose of DNA is generally varied in the range
of 0.1-10 mg/kg. The most favorable dose for rats, rabbits, and mice are 3 mg/kg [87] ,
7 mg/kg [95] , and 0.5-2.5 mg/kg [68] , respectively. The use of permeation enhancers
before hydrodynamic delivery has been shown to decrease the dose required for effi-
cient transfection [96] . Simultaneous injection of chloroquine, an endosmolytic agent,
has shown to enhance and prolong transgene expression significantly [97] .
The hydrodynamic method is widely applicable for delivery of transgene in
important organs such as the liver, kidney, skeleton muscle, heart, lung, and spleen.
All these organs show marked transgene expression, but especially the liver, which
has the highest transgene expression [69,99] . Scientists theorized that the reason
for highest expression in the liver could be the high energetic flow generated by the
large volume of injection and the rapid injection rate, which build up the amount of
injected DNA solution in the inferior vena cava and will push the DNA solution into
associated organs like the liver, kidney, and heart. However, the major part of DNA
solution flows back to liver tissues due to its big size and flexible structure [69,100] .
Another reason for high gene expression in the liver is the porous capillary system
and the significant number of pores measuring about 100-150 nm in hepatic endo-
thelial cells which allows free passage of DNA in the hepatic tissues. In addition,
the pores in the hepatic endothelial cells, the fenestrae, are also responsible for the
entry of a range of molecules in the hepatocytes [100-102] . The study carried out by
the researchers in mice liver with hydrodynamic injection of reporter plasmid in the
hepatic vein showed an increase in injection volume with rapid rate increases gene
expression, and an increase in injection time decreases gene expression [68,73] .
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