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| home > epc > spring 2003 > targeting drugs to the nervous system, fran crawford |
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European Pharmaceutical Contractor
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The nervous system presents important and difficult problems for drug delivery. The acceptable dose of many drugs is limited by central and peripheral side effects. Many drugs are too large or have physical characteristics which restrict permeability through the lipophilic barrier which protects the central nervous system from foreign molecules entering via the blood. This results in many existing drugs having an inadequate therapeutic index and represents a major challenge in the development of new therapeutics.
One new strategy to address these constraints is to anatomically target drugs to the site of disease in the nervous system through axonal transport, systemic sustained release polymers and mucosal delivery.
Axonal Transport
The peripheral nervous system consists of many neurons, some of which can be up to one metre in length. The nerves in the toe, for example, convey electrical impulses between the periphery and the dorsal root ganglion at the spinal cord for onward transmission via a range of mechanisms into the central nervous system. Within each axon there are complex physiological processes occurring in which endogenous molecules are carried up and down the axon (retrograde and anterograde transport). It has been observed by neurosurgeons that fluorescent markers could be transported up the nerve fibres, imaging both the fibre and the DRG (see Figure 1 ), essentially by 'hitching a ride' on the retrograde system.
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