Journal
JOURNAL OF COLLOID AND INTERFACE SCIENCE
Volume 623, Issue -, Pages 1142-1150Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2022.04.158
Keywords
Cubosomes; Poly(2-oxazoline)s; Stabilisers; Lipopolymers; Self-assembly; Lyotropic liquid crystal; Monoolein; lipid nanoparticles
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Funding
- Alexander von Humboldt Foundation
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This study found that lipidic poly(2-oxazoline) polymers can effectively stabilize cubosomes and be used to encapsulate hydrophobic drugs. Compared to commonly used polyethylene glycol stabilizers, these poly(2-oxazoline) polymers have less cytotoxic effects and significantly improve the solubility of poorly water-soluble cancer drugs.
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-2oxazoline) backbone were synthesised using cationic ring-opening polymerisation (PMeOx(40)-OA and PMeOx(80)-OA). The PMeOx(n)-OA stabilised monoolein cubosomes were compared to F-127 cubosomes in particle size, stability, mesophase structure, and biocompatibility. Findings: The obtained PMeOx(n)-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 PMeOx(n)-OA showed lower cytotoxic effect compared to F-127 stabilised cubosomes against OVCAR-3 cells. Furthermore, the PMeOx(n)-OA cubosomes significantly improved the solubility of SN-38, a poorly water-soluble cancer drug. (C) 2022 Elsevier Inc. All rights reserved.
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