Drug Targeting Organ-Specific Strategies

TNFα ng/ml
1.5
1
0.5
0
*
Human (n=4) Rat (n=4)
12.8 Tissue Slices from Other Organs
Precision-cut tissue slices have also been prepared from other organs apart from the liver.
Kidney slices are prepared by the same method as liver slices [73]. Kidney slices from different
species, including man are used in the study of the toxicology and metabolism of drugs
[65,66,73,105–108], organic anion and cation transport [109,110], release of prostaglandin and
noradrenalin [36,111], and also in the study of organ preservation [70,112]. Since region-selective
slices (cortex or medulla slices) can be prepared from the kidney, toxicity and metabolism
in different regions of the kidney can therefore be studied [36,108,113]. Lungs cannot
be sliced directly but need to be filled with 1.5% (w/v) low melting agarose solution containing
0.9% (w/v) NaCl at 37°C and allowed to gel on ice [73]. Lung slices have been used for
drug transport and toxicity studies [114–118]. Up until now slices from other organs have not
been used in the (transport) study of drug targeting devices, but like liver slices, these in vitro
preparations have the potential and advantages to be useful in the study of transport, cellular
processing and efficacy of drug targeting devices. In addition, slices of tumours could be
used to study drug targeting in cancer research.
12.9 Summary and Future Possibilities
12.9 Summary and Future Possibilities 327
Figure 12.10. Production of TNFα by human and rat liver slices in culture medium after 24 h stimulation
with or without 100 µg ml –1 LPS. White bar: control; black bar: 100 µg ml –1 LPS present. Data are the
mean of four experiments ± SEM. *p < 0.05 versus control.
Drug targeting preparations are designed to be used in man, however most research with
these preparations is carried out in animals. Due to known species differences, the study of
these preparations in man in an early stage of development is therefore of paramount importance.
In vitro studies exploiting human tissue can be used to ensure that these drug targeting
devices reach the desired target cells and once there, are effective. When cells in the
liver are the main target, in vitro research should be undertaken using preparations of both
healthy and diseased human liver. As was discussed earlier in this chapter, liver slices seem
like the ideal in vitro preparation for this purpose.The original architecture of the liver is still
intact in the slice, which enables normal intercellular communication and cell-selective distribution
of drugs. Slices can also be used to study drug interactions and the mechanisms and
*