Brain-targeting

Neuroactive agents and neuropeptides (brain-targeted delivery) [266] ... 

Diagnostic agents (e.g., tumor- or brain-targeted delivery). 

M. E. Brewster, K. S. Estes, N. Bodor, Improved Debvery through Biological Membranes. 32. Synthesis and Biological Activity of Brain-Targeted Debvery Systems for Various Estradiol Derivatives , J. Med. Chem. 1988, 31, 244-249. 

Estrogen agonists Estrogen replacement Brain targeted Dabelotine/S-12024 MAO-B inhibitors... 

A. Dalpiaz, C. Contado, E. Vighi, G. Tosi, E. Leo, Preparation and characterization of particulate drug delivery systems for brain targeting, in M.N.V. Ravi Kumar (Ed.), Handbook of Particulate Drug Delivery, Vol. 2. American Scientific Publishers, Stevenson Ranch, CA, 2008. 

Waug J.-X., Suud X., and Zhang, Z.R., Enhanced brain targeting by synthesis of 3,5-dioctanoyl-5-fluoro-2-deoxyuridine and incorporation into sohd hpid nanoparticles, Eur. J. Pharm. Biopharm., 54, 285, 2002. 

Figure 2.3 Serotonin-releasing neurons begin in the raphe nuclei, but project and release serotonin throughout most of the brain. Targets of these neurons include the hippocampus, which is involved in memory, and the amygdala, which is involved in emotions. This diagram shows the pathways of serotonin in the brain.

Physiological permissibility (the presence of a brain target, defining the psychopathological status)... 

Penichet ML, et al. An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting initial applications in anti-HIV antisense drug delivery to the brain. J Immunol 1999 163(8) 4421—4426. 

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. 

Bodor, N., and P. Buchwald. 2003. Brain-targeted drug delivery Experiences to date. Am J Drug Target 1 13. 

Shin, S.U., et al. 1995. Transferrin-antibody fusion proteins are effective in brain targeting. Proc Natl Acad Sci USA 92 2820. 

Olivier, J.C., et al. 1999. Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res 16 1836. 

Jain, S., et al. 2003. RGD-anchored magnetic liposomes for monocytes/neutrophils-mediated brain targeting. Int J Pharm 261 43. 

For example, the BBB can be regarded as a biological membrane that is permeable to most lipophilic compounds but not to hydrophilic molecules, and in most cases, these transport criteria apply to both sides of the barrier. Thus, if a lipophilic compound that can enter the brain is converted there to a hydrophilic molecule, one can assume that it will be locked-in it will no longer be able to come out. Targeting is assisted because the same conversion taking place in the rest of the body accelerates peripheral elimination and further contributes to brain targeting. 

Figure 6 Schematic representation of the molecular packaging and sequential metabolism used for brain targeting of neuropeptides. TRH-CDS (8) is included to provide a concrete illustration for the targetor (T), spacer (S), peptide (P), adjuster (A), and lipophilic (L) moieties. 

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

K. Prokai-Tatrai, L. Prokai, and N. Bodor, Brain-targeted delivery of a leucine-enkephalin analogue by retrometabolic design, J. Med. Chem. 39 4775 (1996). 

K. S. Estes, M. E. Brewster, and N. S. Bodor, Aredox system for brain targeted estrogen delivery causes chronic body weight decrease in rats, Life Sci. 42 1077 (1988). 

Vyas, T. K., Babbar, A. K., Sharma, R. K., and Misra, A. (2005), Intranasal mucoadhe-sive microemulsions of zolmitriptan Preliminary studies on brain-targeting, J. Drug Target., 13, 317-324. 

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