Comparison of cubosomes and hexosomes for the delivery of phenytoin to the brain.

The ability to formulate cubosomes and hexosomes with a single lipid by changing only the colloidal stabiliser presents a unique opportunity to directly compare the biological performance of these uniquely structured nanoparticles. This was explored here via the encapsulation and brain delivery of a model anti-seizure drug, phenytoin, in selachyl alcohol cubosomes and hexosomes. Nanoparticles were prepared with Pluronic® F127 or Tween 80® as the stabiliser and characterised. The internal nanostructure of nanoparticles shifted from hexosomes when using Pluronic® F127 as the stabiliser to cubosomes when using Tween 80® and was conserved following loading of phenytoin, with high encapsulation efficiencies (>97%) in both particle type. Cytotoxicity towards brain endothelial cells using the hCMEC/D3 line was comparable regardless of stabiliser type. Finally, in vivo brain delivery of phenytoin encapsulated in cubosomes and hexosomes after intravenous administration to rats was studied over a period of 60 min, showing cubosomes to be superior to hexosomes, both in terms of brain concentrations and brain to plasma ratio. While the role of stabiliser and/or internal nanostructure remains to be conclusively determined, this study is the first in vivo comparison of cubosomes and hexosomes for the delivery of a therapeutic drug molecule across the BBB and into the brain.