title: Novel RAFT amphiphilic brush copolymer steric stabilisers for cubosomes: poly(octadecyl acrylate)-block-poly(polyethylene glycol methyl ether acrylate).
abstract: Copolymers, particularly Pluronics®, are typically used to sterically stabilise colloidal nanostructured particles composed of a lyotropic liquid crystalline bicontinuous cubic phase (cubosomes). There is a need to design and assess new functionalisable stabilisers for these colloidal drug delivery systems. Six amphiphilic brush copolymers, poly(octadecyl acrylate)-block-poly(polyethylene glycol methyl ether acrylate) (P(ODA)-b-P(PEGA-OMe)), synthesised by reversible addition-fragmentation chain transfer (RAFT), were assessed as novel steric stabilisers for cubosomes. It was found that increasing the density of PEG on the nanostructured particle surface by incorporating a PEG brush design (i.e., brush copolymer), provided comparable and/or increased stabilisation effectiveness compared to a linear PEG structure, Pluronic® F127, which is extensively used for steric stabilisation of cubosomes. Assessment was conducted both prior to and following the removal of the dodecyl trithiocarbonate end-group, by free radical-induced reduction. The reduced (P(ODA)-b-P(PEGA-OMe) copolymers were more effective steric stabilisers for phytantriol and monoolein colloidal particle dispersions than their non-reduced analogues. High throughput characterisation methodologies, including an accelerated stability assay (ASA) and synchrotron small angle X-ray scattering (SAXS), were implemented in this study for the rapid assessment of steric stabiliser effectiveness and lyotropic liquid crystalline phase identification. Phytantriol cubosomes stabilised with P(ODA)-b-P(PEGA-OMe) copolymers exhibited a double diamond cubic phase (Q(2)(D)), whilst monoolein cubosomes exhibited a primitive cubic phase (Q(2)(P)), analogous to those formed using Pluronic® F127.
authors: CSIRO Materials Science and Engineering, Private Bag 10, Clayton, VIC 3169, Australia. Calum.Drummond@rmit.edu.au.
authors: Josephine Y T
authors: JY
authors: Chong
authors: Xavier
authors: X
authors: Mulet
authors: Almar
authors: A
authors: Postma
authors: Daniel J
authors: DJ
authors: Keddie
authors: Lynne J
authors: LJ
authors: Waddington
authors: Ben J
authors: BJ
authors: Boyd
authors: Calum J
authors: CJ
authors: Drummond
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D003102:Colloids / Q000737:chemistry; D020285:Cryoelectron Microscopy; D016503:Drug Delivery Systems; D005609:Free Radicals; D008027:Light; D008055:Lipids / Q000737:chemistry; D050866:Liquid Crystals; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D012542:Scattering, Radiation; D053838:Scattering, Small Angle; D013696:Temperature; D014965:X-Rays
chemical_list: D000179:Acrylates; D003102:Colloids; D005609:Free Radicals; D008055:Lipids; D008689:Methacrylates; C513222:poly(octadecylacrylate); C524499:polyethylene glycol methacrylate; D020442:Poloxamer; D011092:Polyethylene Glycols