Poly(ethylene oxide)–poly(styrene oxide)–poly(ethylene oxide) copolymers: Micellization, drug solubilization, and gelling features

Two new poly(ethylene oxide)–poly(styrene oxide) triblock copolymers (PEO–PSO–PEO) with optimized block lengths selected on the basis of previous studies were synthesized with the aim of achieving a maximal solubilization ability and a suitable sustained release, while keeping very low material expense and excellent aqueous copolymer solubility. The self-assembling and gelling properties of these copolymers were characterized by means of light scattering, fluorescence spectroscopy, transmission electron microscopy, and rheometry. Both copolymers formed spherical micelles (12–14 nm) at very low concentrations. At larger concentration (>25 wt%), copolymer solutions showed a rich phase behavior, with the appearance of two types of rheologically active (more viscous) fluids and of physical gels depending on solution temperature and concentration. The copolymer behaved notably different despite their relatively similar block lengths. The ability of the polymeric micellar solutions to solubilize the antifungal drug griseofulvin was evaluated and compared to that reported for other structurally-related block copolymers. Drug solubilization values up to 55 mg g−1 were achieved, which are greater than those obtained by previously analyzed poly(ethylene oxide)–poly(styrene oxide), poly(ethylene oxide)–poly(butylene oxide), and poly(ethylene oxide)–poly(propylene oxide) block copolymers. The results indicate that the selected SO/EO ratio and copolymer block lengths were optimal for simultaneously achieving low critical micelle concentrations (cmc) values and large drug encapsulation ability. The amount of drug released from the polymeric micelles was larger at pH 7.4 than at acidic conditions, although still sustained over 1 day.

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► Two EOSOEO copolymers with optimized block lengths are proposed as efficient nanocarriers.
► EO33SO14EO33 and EO38SO10EO38 form 13 nm spherical micelles and present a rich phase behavior.
► A great drug solubilization extent with a minimal polymer expense is observed.
► Release rates at pH 5.5 are lower due to a more hydrophobic microenvironment inside the micelle.
► Drug release is Fickian and prompted by micellar rearrangements and drug transfer between micelles.