Intranasal administration of antiretroviral-loaded micelles for anatomical targeting to the brain in HIV

Abstract

We investigated the intranasal administration of poly(ethylene oxide)–poly(propylene oxide) polymeric micelles loaded with high payloads of the first-line antiretroviral drug efavirenz for targeting to the CNS. The effect of micellar size and composition and drug payload was assessed, employing simple micelles made of a highly hydrophilic copolymer, poloxamer F127, loaded with 20 mg/ml drug and mixed micelles containing 75% of a medium hydrophobic poloxamine, T904, and 25% F127 loaded with 20 and 30 mg/ml drug, respectively. F127 confers high physical stability, while T904 substantially improves the encapsulation capacity of the micelles. The bioavailability of the drug in the CNS was increased fourfold and the relative exposure index (ratio between the area-under-the-curve in the CNS and plasma) was increased fivefold with respect to the same system administered intravenously. These findings demonstrate the potential of this scalable and cost-viable strategy to attack the HIV sanctuary in the CNS.