Plant-inspired Pluronic-gallol micelles with low critical micelle concentration, high colloidal stability, and protein affinity.

Polymeric micelles are the most common carriers used for hydrophobic drug delivery. However, they are vulnerable to physiological barriers, such as temperature changes and enzymatic degradation, and can be easily disassembled upon dilution below the critical micelle concentration (CMC) by body fluids after an intravenous injection. Here, we report that Pluronic® micelles with octyl gallate, which is a surfactant containing gallol moieties widely found in antioxidative plant polyphenols, have a low CMC, which improves their colloidal stability without the need for covalent crosslinking. Furthermore, the incorporated gallol moieties provide enzymatic degradation resistance to the micelles owing to their protein affinity, maintaining the hydrophobic cavity of unmodified Pluronic®. Thus, plant-inspired polymeric micelles with low CMC and bioavailability are promising multifunctional vehicles for drug delivery.

Addressing the Shortcomings of Polyphenol-Derived Adhesives: Achievement of Long Shelf Life for Effective Hemostasis.

For rapid and effective hemostasis of uncontrollable bleeding, versatile hemostatic agents have been emerging. Among them, polyphenol-derived adhesives have attracted those hemostatic materials due to instantaneous formation of sticky barriers by robust interactions between the material and the serum proteins from wound. However, a critical challenge in such phenolic materials lies in long-term storage due to spontaneous oxidation under humid environments, leading to changes in hemostatic capability and adhesive strength. Here, we report a transparent hemostatic film consisting of gallol-conjugated chitosan (CHI-G) for minimizing the phenolic oxidation even for 3 months and maintaining strong tissue adhesiveness and its hemostatic ability. The film undergoes a phase transition from solid to injectable hydrogels at physiological pH for efficiently stopping internal and external hemorrhage. Interestingly, the hemostatic capability of the CHI-G hydrogels after 3 month storage depends on (i) the folded microstructure of the polymer with optimal gallol modification and (ii) an initial phase of either a solution state or a solid film. When the hydrogels are originated from the dehydrated film, their successful hemostasis is observed in a liver bleeding model. Our finding would provide an insight for design rationale of hemostatic formulations with long shelf-life.