4
BioTech Sage Report, May 2001
assay and identify drug candidates
consistently is a huge obstacle in
drug discovery. Advances in
nanotechnology will yield signifi-
cant improvements in this area.
Continuing discoveries will lead to
innovative synthetic routes, new
processing strategies, and more eco-
nomical manufacturing. Big Pharma
projects nearly a tenfold increase in
the number of drug compounds that
will be evaluated this year compared
to 1998, with only modest minia-
turization of technology.
BSR believes there are compa-
nies who have the means to facili-
tate this largely unmet area. Two in
particular are
Caliper Technology
and
ACLARA BioSciences. Both
have developed high throughput
systems designed to perform high-
volume experimentation, on the or-
der of tens of thousands of experi-
ments per day per chip, using nano-
liters of reagents, and performed on
a system that fits on a bench. The
benefits of the microfluidic chip en-
vironment are several: reduced in-
strument size, enabling decentraliza-
tion of high throughput screening;
integrated reagent handling, leading
to enhanced productivity; up to a ten
thousandfold reduction in com-
pound library use; up to a one hun-
dred thousandfold reduction in tar-
get use for high-throughput screen-
ing; reduction in the cost per data
point generated, leading to greater
overall institutional efficiency; and
higher-quality, more-reproducible
results. As the molecular targets
used in high-throughput screening
assays represent promising targets
for many serious diseases, the bene-
fits of lab-on-a-chip systems are
faster and more efficient discoveries
of life-saving new drugs.
Both companies are poised to
deliver instrumentation and supplies
to the market. However, given the
fact that Caliper is collaborating
with Agilent to sell instruments,
BSR believes Caliper will have the
advantage.
Drug delivery
The challenge is to develop and
deploy nanoparticles for delivering
drugs, gene therapies, and other
therapeutics. These technologies
will deliver drugs or other molecules
that are hard to dissolve, and may
even transport them directly to their
site of action. Such nanoparticles
will be used to treat cancer and a
wide range of other diseases.
Many drugs that work well in
the test tube fail in the body because
they will only dissolve in fluids that
cause undesirable side effects, or
they become trapped in other parts
of the body than where they are
needed. Evidence has shown that
using nanoparticle delivery for wa-
ter-insoluble or unstable drugs could
facilitate the distribution of those
drugs, whose chemical structure
must be modified to improve their
solubility.
Furthermore, most drugs are
now delivered throughout the body,
rather than to the specific area
where they are meant to have an ef-
fect. As a result, side effects on
other tissues are unavoidable, and
often are the reason why so many
drugs fail clinical trials. Nanoparti-
cles show promise for the delivery
of drugs to specific tissues where
they are required. By directing drugs
primarily to their desired site of ac-
tion, lower overall doses of drugs
will be given, because these will
concentrate where they are needed
and exposure of other body tissues
to the drugs will be significantly re-
duced. This, in turn, will reduce un-
desirable side effects of the drugs
and increase the approval potential
with the Food and Drug Administra-
tion. A proof-of-principle study
with a prototype microchip device
capable of controlled-release drug
delivery has been successful. Proper
selection of biocompatible device
materials may result in the develop-
ment of a controlled-release implant
(pharmacy-on-a-chip) or a highly
controlled tablet (smart tablet) for
drug delivery applications.
In gene therapy, specific target-
