The problems encountered in the treatment of human herpes simplex virus type 1 and type 2 infections have been attributed to the inability of antiviral agents to attain optimal concentrations at the site of viral infection. To circumvent these problems utilization of the novel chemical delivery system (analogous to the NADH leads to NAD+ redox system) developed by Bodor and associates is proposed. This system is based on the interconversion of lipophilic dihydropyridines which readily cross BBB and hydrophilic pyridinium salts which are """"""""locked"""""""" in the brain. The advantages of this system are 1) lower peripheral concentrations of the active agent and consequently reduced systemic toxicity 2) greater efficacy since a lower dose can be given to attain clinically effective cerebral concentrations. The specific goal of this proposal is to apply the chemical delivery system to selected antiherpetic agents to facilitate delivery across biological membranes. Considering the incidence and the devasting effects of herpes simplex infections in humans, there is a need for new innovative research especially in the development of targeted antiherpetic agents through effective delivery systems.
