Lipidic poly(2-oxazoline)s as PEG replacement steric stabilisers for cubosomes

Titelangaben

Rajesh, Sarigama ; Leiske, Meike N. ; Leitch, Victoria ; Zhai, Jiali ; Drummond, Calum J. ; Kempe, Kristian ; Tran, Nhiem:
Lipidic poly(2-oxazoline)s as PEG replacement steric stabilisers for cubosomes.
In: Journal of Colloid and Interface Science. Bd. 623 (2022) . - S. 1142-1150.
ISSN 1095-7103
DOI: https://doi.org/10.1016/j.jcis.2022.04.158

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Abstract

Hypothesis
Cubosomes are promising delivery vehicles for a wide range of drugs and biomolecules. Polymers such as the polyethylene glycol (PEG)-based Pluronic F-127 have been widely used for dispersing and stabilising lipid cubosomes. However, due to the PEG-immunogenicity, and pre-existing anti-PEG antibodies in some individuals, the efficacy of PEG-stabilised nanomedicines has been reduced. In this study, we hypothesise that lipidic poly(2-oxazoline)s have the potential to stabilise cubosomes, which can be used to encapsulate a hydrophobic drug similar to cubosomes stabilised with F-127.
Experiments
Two lipidic polymers consisting of an oleyl (OA) chain connected to a poly(2-methyl-2-oxazoline) backbone were synthesised using cationic ring-opening polymerisation (PMeOx40-OA and PMeOx80-OA). The PMeOxn-OA stabilised monoolein cubosomes were compared to F-127 cubosomes in particle size, stability, mesophase structure, and biocompatibility.
Findings
The obtained PMeOxn-OA were well-defined (low dispersity) and had a high degree of OA functionalisation (≥95). These polymers were as good as F-127 in producing well dispersed monoolein cubosomes and maintained the internal cubic structure. The cubosomes stabilised with PMeOxn-OA showed lower cytotoxic effect compared to F-127 stabilised cubosomes against OVCAR-3 cells. Furthermore, the PMeOxn-OA cubosomes significantly improved the solubility of SN-38, a poorly water-soluble cancer drug.