title: Stabilising cubosomes with Tween 80 as a step towards targeting lipid nanocarriers to the blood-brain barrier.
abstract: Coating nanoparticles with the surfactant Tween 80 have been previously shown to enhance drug delivery across the blood-brain barrier (BBB). The aim of this study was to investigate whether Tween 80 could be used to stabilise phytantriol-based cubosomes thereby enabling potential application in delivering macromolecular therapeutics to the brain. Cubosome particles with their large internal and external surface area by virtue of their nanostructure are ideal for delivery of macromolecules. Phase behaviour studies were conducted using a combination of optical microscopy and small-angle X-ray scattering (SAXS) and the addition of Tween 80 to mixtures of phytantriol and water resulted in a rich array of lyotropic mesophases. In particular, a large cubic phase region and a two-phase region of readily dispersed cubosomes is observed. Cubosomes with different concentrations of Tween 80 and phytantriol as the liquid crystal forming lipid were prepared using the solvent precursor method and their physical properties were investigated. A combination of dynamic light scattering, cryogenic electron tomography and SAXS shows formation of well-defined cubosomes with a narrow size distribution and the Im3m cubic structure. Collectively, the results confirm that Tween 80 can effectively stabilize phytantriol cubosomes, opening the possibility for future application in drug delivery across the BBB. Moreover, well-defined, homogenous cubosome formulations prepared using the mild solvent precursor dilution method has significant implications for large-scale production of cubosomes, which currently is a major barrier to the application of cubosomes in the clinic.
authors.affiliation: School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, 9054 Dunedin, New Zealand.
authors.forename: Hanisah
authors.initials: H
authors.lastname: Azhari
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Munich, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Strauss
authors.affiliation: School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, 9054 Dunedin, New Zealand.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Pde, Parkville, VIC 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.affiliation: School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, 9054 Dunedin, New Zealand. Electronic address: shakila.rizwan@otago.ac.nz.
authors.forename: Shakila B
authors.initials: SB
authors.lastname: Rizwan
mesh_terms: D001812:Blood-Brain Barrier; D004337:Drug Carriers; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles; D011136:Polysorbates / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D011136:Polysorbates
keywords: Blood–brain barrier; Cryogenic electron tomography (cryo-ET); Cubosomes; Phytantriol; Pluronic F127; Tween 80