Diego A Chiappetta1, Christian Hocht, Javier A W Opezzo, Alejandro Sosnik. 1. The Group of Biomaterials & Nanotechnology for Improved Medicines (BIONIMED), Department of Pharmaceutical Technology, Faculty of Pharmacy & Biochemistry, University of Buenos Aires, 956 Junín St, 6th Floor, Buenos Aires CP1113, Argentina.
Abstract
AIM: To investigate 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. METHODS & MATERIALS: 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 poloxamine of intermediate hydrophobicity, T904, and 25% F127 loaded with 20 and 30 mg/ml drug. F127 confers high physical stability, while T904 substantially improves the encapsulation capacity of the micelles. RESULTS: 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. CONCLUSION: These findings demonstrate the potential of this scalable and cost-viable strategy to address the HIV sanctuary in the CNS.
AIM: To investigate 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. METHODS & MATERIALS: 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 poloxamine of intermediate hydrophobicity, T904, and 25% F127 loaded with 20 and 30 mg/ml drug. F127 confers high physical stability, while T904 substantially improves the encapsulation capacity of the micelles. RESULTS: 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. CONCLUSION: These findings demonstrate the potential of this scalable and cost-viable strategy to address the HIV sanctuary in the CNS.