complex formation with other macromolecules, alter their size and properties as a
function of site within the body. The impact of these variables on biodistribution
and elimination is not known. Finally, most current pharmacokinetic approaches
are based on biodistribution within the vascular system as the distribution compart-
ment. However, the particulate and hydrophobic nature of some nanomaterials may
target them to the lymphatic system. Although this may be beneficial when target-
ing immune modulating drugs, it may be disadvantageous for other nanomaterials.
7 High-Throughput Screening
Many aspects of modern chemistry and biology have been automated and this
enables the biological activity of drugs, as well as their adverse effects, to be
screened rapidly without a requirement for detailed hypothesis-driven research.
All aspects of early drug discovery and development are influenced by this increas-
ingly automated “brute-force” approach. Combinatorial chemistry allows the gen-
eration of large numbers of study compounds with the potential for use for specific
therapeutic targets. These libraries of compounds may contain tens of thousands of
chemical entities sharing a common chemical motif. High throughput screens can
then be used to select compounds with desirable pharmacokinetic (ADME) proper-
ties or for the greatest efficacy or potency in in vitro tests (e.g. cloned receptor
assays, micro-arrays directed against specific therapeutic targets). Additional tests
directed at the assessment of toxicological potential can then be used to further
exclude less desirable compounds as candidate drugs. These approaches are
currently in use for many drug classes developed for use in humans.
The future holds great promise as components of these systems are validated and
transferred to other applications. As this pyramid of increasingly sophisticated tests
is explored and developed, whole cell in vitro assays may then be used to assess
whether similar responses are obtained in more complex biological systems. In
vitro tests to assess the biotransformation of candidate drugs by specific enzymes
can be rapidly accomplished. In vivo trials can then be conducted frequently with
several compounds being dosed simultaneously using the so-called cassette phar-
macokinetic designs, to obtain an initial estimate of ADME parameters (Hsieh and
Korfmacher 2006 ). Individual compound studies will then be conducted to validate
these rapid screening tests which assume that drug–drug interactions do not occur at
the low doses used. The rapid advances in analytical chemistry that allow quantifi-
cation with increased sensitivity levels as well as specificities allow these multiple
drug studies to be conducted in economical and well characterised laboratory
animals, selected for similarity to the veterinary target species, of interest. Finally,
the miniaturisation of all aspects of the several automated processes, discussed
above in microfluidic and nanomaterial sections, will further increase speed, whilst
decreasing the size and cost of integrated systems. As these approaches become
more successful for human therapeutics and, as a result, cost and ease of use further
decrease, increased application to targeted veterinary applications could occur.
New Technologies for Application to Veterinary Therapeutics 203