LAUSR

We investigated the potential of a self-assembled lipid nanocarrier, cubosomes, to improve delivery of incorporated cargo to the brain in vivo in zebrafish. Cubosomes were formulated with the surfactants Pluronic F68 or Pluronic F127 or Tween 80, with the hypothesis that Tween 80 will enhance brain targeting as previously shown for polymeric nanoparticles. The physiochemical properties and the ability of the cubosomes to facilitate delivery of the model drug lissamine rhodamine (RhoB) into the brain was investigated. Distribution of cubosomes in the midbrain was also investigated by ultrastructural analysis via incorporation of octanethiol-functionalized gold nanoparticles. Cubosomes were typically 165-195 nm in size with a Pn3m (Pluronic-stabilized) or Im3m (Tween 80) cubic phase internal structure. Cubosomes were injected intravenously into larvae (12 to 14 days post fertilization) and the concentration of RhoB in the midbrain was determined by quantifying the fluorescence intensity of RhoB. Uptake of RhoB was significantly greater in larvae injected with Tween 80 stabilized cubosomes as compared to a control suspension of RhoB or cubosomes stabilized with Pluronics. Collectively, we show for the first time that cubosomes can be functionalized to deliver drug across the BBB, offering new opportunities to overcome drug delivery issues across this formidable biological barrier.