IMPROVED DELIVERY OF ANTIVIRALS FOR CNS INFECTIONS

HUMAN CYTOMEGALOVIRUS (HCMV) IS A COMMON AND NOT USUALLY SERIOUS INFECTIVE AGENT. HOWEVER, IN THE CASE OF ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) AND OTHER IMMUNO-SUPPRESSEDSTATES, HCMV IS INORDINATELY VIRULENT AND IS EVEN A MAJOR CAUSE OF DEATH. RECENTLY, TREATMENT OF HCMV INFECTIONS IN IMMUNOSUPPRESSED STATES HAS BEEN DRAMATICALLY IMPROVED THROUGH THE INTRODUCTION OF A NEW ANTIVIRAL COMPOUND, 9-(1,3-DIHYDROXY)-2-PROPOXYMETHYL)GUANINE, DHPG, WHICH IS ALSO KNOWN AS GANCICLOVIR. HCMV INFECTIONS OF THE CENTRAL NERVOUS SYSTEM (CNS) ARE, HOWEVER, RESISTANT TO ANTIVIRAL THERAPY, DUE MAINLY TO THE PRESENCE OF THE BLOOD-BRAIN BARRIER (BBB), WHICH EFFECTIVELYPREVENTS ACCESS TO THE CNS OF HYDROPHILIC COMPOUNDS SUCH AS DHPG. WE PROPOSE TO INVESTIGATE THE APPLICATION OF A CHEMICAL DELIVERY SYSTEM (CDS) FOR DELIVERY OF DHPG TO THE CNS. THIS WORK WOULD INVOLVE SYNTHESIS OF SEVERAL COMPOUNDS, INVESTIGATION OF THEIR PHYSICAL AND CHEMICAL PROPERTIES, AND INITIAL STUDY OF THEIR DISTRIBUTIONAL PROFILES IN ANIMAL MODELS.