Abstract
Summary
The delivery of drugs to central nervous system (CNS) is a challenge in the
treatment of neurological disorders. Drugs may be administered directly into
the CNS or administered systematically (e.g., by intravenous injection) for
targeted action in the CNS. The major challenge to CNS drug delivery is the
blood-brain barrier (BBB), which limits the access of drugs to the brain
substance.
Advances in understanding of the cell biology of the BBB have opened new
avenues and possibilities for improved drug delivery to the CNS. Several
carrier or transport systems, enzymes, and receptors that control the
penetration of molecules have been identified in the BBB endothelium.
Receptor-mediated transcytosis can transport peptides and proteins across the
BBB. Methods are available to assess the BBB permeability of drugs at the
discovery stage to avoid development of drugs that fail to reach their target
site of action in the CNS.
Various strategies that have been used for manipulating the blood-brain
barrier for drug delivery to the brain include osmotic and chemical opening of
the blood-brain barrier as well as the use of transport/carrier systems. Other
strategies for drug delivery to the brain involve bypassing the BBB. Various
pharmacological agents have been used to open the BBB and direct invasive
methods can introduce therapeutic agents into the brain substance. It is
important to consider not only the net delivery of the agent to the CNS, but
also the ability of the agent to access the relevant target site within the
CNS. Various routes of administration as well as conjugations of drugs, e.g.,
with liposomes and nanoparticles, are considered. Some routes of direct
administration to the brain are non-invasive such as transnasal route whereas
others involve entry into the CNS by devices and needles such as in case of
intrathecal and intracerebroventricular delivery. Systemic therapy by oral and
parenteral routes is considered along with sustained and controlled release to
optimize the CNS action of drugs. Among the three main approaches to drug
delivery to the CNS - systemic administration, injection into CSF pathways,
and direct injection into the brain - the greatest developments is anticipated
to occur in the area of targeted delivery by systemic administration.
Many of the new developments in the treatment of neurological disorders will
be biological therapies and these will require innovative methods for
delivery. Cell, gene and antisense therapies are not only innovative
treatments for CNS disorders but also involve sophisticated delivery methods.
RNA interference (RNAi) as a form of antisense therapy is also described.
The role of drug delivery is depicted in the background of various therapies
for neurological diseases including drugs in development and the role of
special delivery preparations. Pain is included as it is considered to be a
neurological disorder. Cell and gene therapies will play an important role in
the treatment of neurological disorders in the future.
The method of delivery of a drug to the CNS has an impact on the drug' s
commercial potential. The market for CNS drug delivery technologies is
directly linked to the CNS drug market. Values are calculated for the total
CNS market and the share of drug delivery technologies. Starting with the
market values for the year 2008, projections are made to the years 2013 and
2018. The markets values are tabulated according to therapeutic areas,
technologies and geographical areas. Unmet needs for further development in
CNS drug delivery technologies are identified according to the important
methods of delivery of therapeutic substances to the CNS. Finally suggestions
are made for strategies to expand CNS delivery markets. Besides development of
new products, these include application of innovative methods of delivery to
older drugs to improve their action and extend their patent life.
Profiles of 70 companies involved in drug delivery for CNS disorders are
presented along with their technologies, products and 65 collaborations. These
include pharmaceutical companies that develop CNS drugs and biotechnology
companies that provide technologies for drug delivery. A number of cell and
gene therapy companies with products in development for CNS disorders are
included. References contains over 400 publications that are cited in the
report. The report is supplemented with 50 tables and 9 figures.
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