Assembly and Degradation of Low-Fouling Click-Functionalized Poly(ethylene glycol)-Based Multilayer Films and Capsules

Nano‐/micrometer‐scaled films and capsules made of low‐fouling materials such as poly(ethylene glycol) (PEG) are of interest for drug delivery and tissue engineering applications. Herein, the assembly and degradation of low‐fouling, alkyne‐functionalized PEG (PEGAlk) multilayer films and capsules, which are prepared by combining layer‐by‐layer (LbL) assembly and click chemistry, are reported. A nonlinear, temperature‐responsive PEGAlk is synthesized, and is then used to form hydrogen‐bonded multilayers with poly(methacrylic acid) (PMA) at pH 5. The thermoresponsive behavior of PEGAlk is exploited to tailor film buildup by adjusting the assembly conditions. Using alkyne–azide click chemistry, PEGAlk/PMA multilayers are crosslinked with a bisazide linker that contains a disulfide bond, rendering these films and capsules redox‐responsive. At pH 7, by disrupting the hydrogen bonding between the polymers, PEGAlk LbL films and PEGAlk‐based capsules are obtained. These films exhibit specific deconstruction properties under simulated intracellular reducing conditions, but remain stable at physiological pH, suggesting potential applications in controlled drug release. The low‐fouling properties of the PEG films are confirmed by incubation with human serum and a blood clot. Additionally, these capsules showed negligible toxicity to human cells. Multilayer degradable PEG‐based capsules are made of a nonlinear click‐ functionalized poly(ethylene glycol). These capsules exhibit excellent low‐fouling behavior against human thrombi (blood clots). Together with the specific degradation characteristics, these properties make the PEG‐based capsules promising for drug delivery applications.