A novel chemical delivery system for brain targeting

Two different chemical approaches for brain drug delivery and targeting are proposed in the present review. One is a chemical drug delivery using a ri ng-closure reaction to the hydrophilic quaternary thiazolium compound in th e brain. The other is a chemical drug targeting utilizing the nutrient rece ptor (transporter) system on the blood-brain barrier. The brain delivery sy stem has been optimized and it was demonstrated that the brain delivery of three drugs, a drug for Parkinson's disease, an excitatory amino acid antag onist and a free radical scavenger, were improved by the conjugation with c is-2-formylaminoethenylthio derivatives in vivo. As for the brain targeting system, it was demonstrated that the conjugation with L-Glu improved the d rug's brain distribution via the L-Glu excitatory and/or transport receptor s in vitro and in vivo. These findings suggest that the concepts of two che mical approaches will contribute to the development of new central nervous system drugs. (C) 1999 Elsevier Science B.V. All rights reserved.