Chemical delivery system brain targeting

In principle, many targetor moieties are possible for a general system of this kind [119, 122-125], but the one based on the 1,4-dihydrotrigonelline trigonelline (coffearine) system, where the lipophilic 1,4-dihydro form (T) is converted in vivo to the hydrophilic quaternary form (T ), proved the most useful. This conversion takes place easily everywhere in the body since it is closely related to the ubiquitous NADH NAD coenzyme system associated with numerous oxidoreductases and cellular respiration [126, 127]. Since oxidation takes place with direct hydride transfer [128] and without generating highly active or reactive radical intermediates, it provides a non-toxic targetor system [129]. Furthermore, since for small quaternary pyridinium ions rapid elimination from the brain, probably due to involvement of an active transport 

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Bodor, N., et al. 2002. In vitro and in vivo evaluations of dihydroquinoline- and dihydroisoquinoline-based targetor moieties for brain-specific chemical delivery systems. J Drug Target 10 63. 

L. Prokai, K. Prokai-Tatrai, N. Bodor, Targeting Drugs to the Brain by Redox Chemical Delivery Systems , Med. Res. Rev. 2000, 20, 367-416. 

Rrokai, L., K. Rrokai-Tatrai, and N. Bodor, Targeting drugs to the brain by redox chemical delivery systems. Med Res Rev, 2000. 20(5) 367 16. 

Yoshikawa T., Sakaeda T., Sugawara T., Hirano K., and Stella V. J. (1999). A novel chemical delivery system for brain targeting. Adv. Drug Deliv. Rev. 36 255-275. 

N. Bodor and P. Buchwald, Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems, Adv. Drug Delivery Rev. 36 229 (1999). 

G. Somogyi, S. Nishitani, D. Nomi, P. Buchwald, L. Prokai, and N. Bodor, Targeted drug delivery to the brain via phosphonate derivatives. I. Design, synthesis, and evaluation of an anionic chemical delivery system for testosterone, Int. J. Pharm. 166 15 (1998). 

Tissue targeting may also be directed at tumors through the use of monoclonal antibodies, as briefly mentioned earlier. Finally, brain targeting can also be attempted with the prodrug approach, as exemplified by estradiol by use of a redox-based chemical delivery system (174). 

Figure 15.41. Deliveiy of kyotorphin analogs was achieved using both using a chemical delivery system (131) and a brain-targeted redox analog (132) approach.

Brewster, M.E. Druzgala, P.J. Anderson, W.R. Huang, M.-J. Bodor, N. Pop, E. Efficacy of a 3-substi-tuted versus 17-substituted chemical delivery system for estradiol brain targeting. J.Pharm.Sci., 1995, 84, 38-43... 

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