Recent advances in the brain targeting of neuropharmaceuticals by chemicaldelivery systems

Brain-targeted chemical delivery systems represent a general and systematic method that can provide localized and sustained release for a variety of t herapeutic agents including neuropeptides. By using a sequential metabolism approach, they exploit the specific trafficking properties of the blood-br ain barrier and provide site-specific or site-enhanced delivery. After a br ief description of the design principles, the present article reviews a num ber of specific delivery examples (zidovudine, ganciclovir, lomustine benzy lpenicillin, estradiol, enkephalin, TRH, kyotorphin), together with represe ntative synthetic routes, physicochemical properties, metabolic pathways, a nd pharmacological data. A reevaluated correlation for more than 60 drugs b etween previously published in vivo cerebrovascular permeability data and o ctanol/water partition coefficients is also included since it may be useful in characterizing the properties of the blood-brain barrier, including act ive transport by P-glycoprotein. (C) 1999 Elsevier Science BN. All rights r eserved.