MICRODROPLET-BASED SUSTAINED DELIVERY OF AZIDOTHYMIDINE

THE FORMATION OF MICRODROPLET FORMULATIONS OF A DRUG, A MEANS OF IMPROVING TISSUE COMPATIBILITYAND OF PROVIDING SUSTAINED RELEASE, INVOLVES THE PREPARATION OF MICROSPHERES (O.1 MICRON DIAMETER) OF A DRUG-CONTAINING OIL PHASE, AND THEIR ENCAPSULATION WITH A LAYER OF PHOSPHOLIPID.A RAT MODEL WILL BE USED TO TEST THE MICRODROPLET TECHNOLOGY-BASED SUSTAINED DELIVERY OF AZIDOTHYMIDINE, WHICH IS INTENDED TO PROVIDE UP TO A ONE WEEK TREATMENT REGIMEN FOR HIV INFECTION. A SERIES OF MICRODROPLET FORMULATIONS CONTAINING DIFFERENT CONCENTRATIONS OF AZIDOTHYMIDINE WILL BE PREPARED IN AT LEAST THREE TISSUE-COMPATIBLE AND FDA-APPROVED SYNTHETIC OILS. THE DRUG RELEASE KINETICS OF THE AZT-CONTAINING MICRODROPLETS WILL BE TESTED IN AN IN VITRO MODEL AS WILL AS BY INTRADERMAL AND INTRAMUSCULAR INJECTIONS INTO RATS. A FORMULATION WHICH PROVIDES ACCEPTABLE (I.E. ZERO ORDER) RELEASE KINETICE OVER A PERIOD OF ONE WEEK WILL BE IDENTIFIED FOR FURTHER DEVELOPMENT IN PHASE II.