Brain Drug Targeting: The Future of Brain Drug Development by William M. Pardridge

By William M. Pardridge

During this leading edge and hard e-book, William Pardridge, an international chief within the learn of the blood-brain barrier and its scientific implications, argues that mind drug improvement has been constrained through the failure of sufficient mind drug focusing on. this is often an more and more pressing challenge as advancements in genomics bring about new generations of healing macromolecules. the writer stories the sector of neurotherapeutics from the perspective of drug focusing on. He surveys the clinical and medical foundation of drug supply throughout organic membranes, together with themes resembling genetically engineered trojan horses for drug concentrating on, antisense neurotherapeutics, and gene treatment of mind issues. At a time while there are few major new medicines in prospect for universal neurological ailments, this authoritative evaluate will inspire a variety of clinicians and neuroscientists to reexamine the improvement and use of substances in treating issues of the principal anxious method.

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5 mm. Therefore, there has been minimal diffusion of the NGF from the site of implantation at 48 h after administration. , Distribution of nerve growth factor following direct delivery to brain interstitium, 196–206, copyright (1995), with permission from Elsevier Science. 15 ␮l/min for a total infusate volume of 75 ␮l. Bilateral cannulas were positioned stereotactically in the corona radiata. The magnification bar is 5 mm. From Morrison et al. (1994) with permission. 7A) is minimal owing to the poor penetration into tissue of drugs by diffusion.

The surface area of the BBB is 180 cm2 per gram brain (Crone, 1963). 3). 021 m2 in the human brain (Dohrmann, 1970). Therefore, the surface area of the BBB is Ͼ1000-fold greater than the surface area of the choroid plexus epithelium, which forms the blood–CSF barrier. The large BBB surface area means the extent to which a given molecule in blood enters brain parenchyma is determined solely by the permeability characteristics of the BBB. The distribution of circulating drug into brain via the transport through the blood–CSF barrier followed by diffusion into brain is minimal, owing to rapid export of drugs and solutes from CSF to blood.

Atively lipophilic molecule that enters CSF by transport across the choroid plexus barrier via lipid mediation (Thomas and Segal, 1997). , 1997). Any AZT that passively influxes into brain is rapidly extruded from brain back to blood by BBB active efflux systems (Chapter 3). Brain barrier surface area The two barriers in brain have vastly different surface areas. The surface area of the BBB is 180 cm2 per gram brain (Crone, 1963). 3). 021 m2 in the human brain (Dohrmann, 1970). Therefore, the surface area of the BBB is Ͼ1000-fold greater than the surface area of the choroid plexus epithelium, which forms the blood–CSF barrier.

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