IMPROVED DELIVERY THROUGH BIOLOGICAL-MEMBRANES - THE EFFECT OF DIHYDRONICOTINATE N-SUBSTITUTION ON THE BRAIN-TARGETING EFFICACY OF A ZIDOVUDINE CHEMICAL DELIVERY SYSTEM

Enhanced brain delivery of zidovudine (AZT) has been demonstrated usin g a redox-based chemical delivery system (CDS). Optimization of the pr ototype AZT-CDS pyridin-3-yl)carbonyl]-3'-azido-3'-deoxythymidine) was investigated by manipulation of the N-methyl group present on the dih ydronicotinate portion of the molecule and examining the release of AZ T in vivo in a rat model. Of the five compounds examined, all produced higher brain levels and lower blood levels of AZT than did AZT itself . In comparing the novel AZT-CDS analogues to the N-methyl benchmark, the N-propyl system proved to be the most efficient of the compounds t ested.