Novel RAFT amphiphilic brush copolymer steric stabilisers for cubosomes: poly(octadecyl acrylate)- block-poly(polyethylene glycol methyl ether acrylate)

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.