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Lyotropic liquid crystalline nanostructured particles (e.g., cubosomes and hexosomes) are being investigated as delivery systems for therapeutics in biomedical and pharmaceutical applications. Long term stability of these particulate dispersions is generally provided by steric stabilizers, typically commercially available amphiphilic copolymers such as Pluronic F127. Few examples exist of tailored molecular materials designed for lyotropic liquid crystalline nanostructured particle stabilization. A library of PEGylated-phytanyl copolymers (PEG-PHYT) with varying PEG molecular weights (200-14K Da) was synthesized to assess their performance as steric stabilizers for cubosomes and to establish structure-property relationships. The PEGylated-lipid copolymers were first found to self-assemble in excess water in the absence of cubosomes and also displayed thermotropic liquid crystal phase behavior under cross-polarized light microscopy. An accelerated stability assay was used to assess the performance of the copolymers, compared to Pluronic F127, for stabilizing phytantriol-based cubosomes. Several of the PEGylated-lipid copolymers showed steric stabilizer effectiveness comparable to Pluronic F127. Using synchrotron small-angle X-ray scattering and cryo-transmission electron microscopy, the copolymers were shown to retain the native internal lyotropic liquid crystalline structure, double diamond cubic phase (Q2 D), of phytantriol dispersions; an important attribute for controlling downstream performance.
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