The major objective of the present project
is to develop new therapeutic strategies for the treatment of
brain diseases. The aim is to restore, maintain and improve
cell, tissue and organ functions within the Central Nervous
System (CNS). Emphasis is on two kinds of diseases: brain cancer
and neurodegenerative disorders, namely Parkinson's and Huntington's
Disease. The treatment of CNS diseases is very difficult due
to the Blood Brain Barrier, which hinders most drugs from reaching
the brain tissue.
Thus, target-specific delivery systems
are required. Using a multi-disciplinary approach we will develop
new biodegradable microparticles and implants releasing highly
potent drugs in a controlled manner into the CNS. The whole
range of innovation, from advanced research, through technological
development up to in vivo evaluation in animal models will be
covered. With an industrial company being part of the consortium,
we foresee the economic exploitation of the outcoming scientific
The major objective of this project is
to develop new and improved therapeutic strategies for health
care, in particular for the treatment of brain diseases. The
aim is to restore, maintain and improve cell, tissue and organ
functions in the Central Nervous System (CNS).
Emphasis is on the treatment of two kinds
- Brain cancer.
- Neurodegenerative disorders, such as Parkinson's and Huntington's
The treatment of CNS-diseases is extremely
difficult because of the Blood-Brain-Barrier (BBB). Only low
molecular mass lipid-soluble molecules, and a few peptides and
nutrients can cross this barrier to a significant extent, either
by passive diffusion or using specific transport mechanisms.
Thus, for most drugs it is difficult to achieve therapeutic
levels within the brain tissue. In addition, highly potent drugs
(e.g., anticancer drugs and neurotrophic factors) that may be
necessary to be delivered to the CNS, often cause serious toxic
side effects when administered systemically. Thus, target-specific
delivery systems, providing the transport of the drugs exclusively
to the brain tissue are highly desireable.
DESCRIPTION OF THE WORK
The workplan will be broken down into four
individual, multi-disciplinary work packages (WPs):
- Understanding the mechanisms involved in target-specific
drug delivery to cns cells.
- Development of new biodegradable microparticles for intracranial
- Development of new pre-programmemable biodegradable intracranial
- In vivo testing of the newly developed therapeutic strategies.
WP1 aims at gaining new scientific knowledge
about the transport mechanisms involved in drug release from
controlled drug delivery systems into the brain tissue. This
information is essential for an intelligent design of both types
of new intracranial systems: new biodegradable microparticles
and new pre-programmemable implants. Various physico-chemical
methods will be used to characterise the newly developed pharmaceutical
WPs2 and 3 encompass both, the optimisation
of the design parameters and the development of suitable experimental
methods to manufacture these systems in a laboratory and industrial
scale. Particular attention will be paid to the biological activity
of the incorporated drugs, e.g. proteins risk loosing their
pharmacodynamic activity when exposed to liquid-liquid interfaces.
Adequate precautions will be taken and the biological activity
will be monitored with cell culture tests.
For the evaluation of the in vivo performance
of the newly developed devices, WP4 encompasses animal studies
for both types of diseases (brain tumour and neurodegenerative
disorders). The results obtained will be essential to provide
immediate feedback to the other WPs. The in vivo data will be
used to optimise the design of the new systems and evaluate
the theories concerning the drug transport mechanisms. Particular
attention will be paid to the establishment of possible in vitro/in
vivo correlations, allowing the minimisation of the required
number of animal studies to test and optimise the new pharmaceutical
- Determination of the mechanisms involved in target-specific
drug delivery to CNS cells.
- Development of new biodegradable microparticles and intracranial
implants being able to release highly potent drugs at optimal,
pre-determined rates into the brain tissue.
- In vivo evaluation of promising candidates in animal models
for brain tumor and neurodegenerative disorders.
- Transfer of the obtained new scientific knowledge to industrial
applications, e.g., scale-up of manufacturing procedures.
|| Achim Goepferich
College of Pharmacy
93040 Regensburg, Germany
Tel: +49 9419434842
Fax: +49 9419434807
Alexander T Florence
School of Pharmacy
University of London
WC1N 1AX London, United Kingdom
Tel: +44 2077535819
Fax: +44 2078375092
School of Medicine
University of Angers
49045 Angers, France
Tel: +33 241354822
Fax: +33 241354508