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 sta-biliser 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 pre -pared with Pluronic (R) F127 or Tween 80 (R) as the stabiliser and characterised. The internal nanostructure of nanoparticles shifted from hexosomes when using Pluronic (R) F127 as the stabiliser to cubosomes when using Tween 80 (R) 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 cubo-somes 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 deter-mined, this study is the first in vivo comparison of cubosomes and hexosomes for the delivery of a ther-apeutic drug molecule across the BBB and into the brain. (C) 2021 Published by Elsevier Inc.

Automated summary

The study explored the formulation of cubosomes and hexosomes with different stabilizers, encapsulation of an anti-seizure drug, and compared their in vivo brain delivery in rats. Cubosomes showed superiority in brain concentrations and brain to plasma ratio compared to hexosomes.