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

Abstract

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 (PEG(Alk) ) multilayer films and capsules, which are prepared by combining layer-by-layer (LbL) assembly and click chemistry, are reported. A nonlinear, temperature-responsive PEG(Alk) is synthesized, and is then used to form hydrogen-bonded multilayers with poly(methacrylic acid) (PMA) at pH 5. The thermoresponsive behavior of PEG(Alk) is exploited to tailor film buildup by adjusting the assembly conditions. Using alkyne-azide click chemistry, PEG(Alk)/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, PEG(Alk) LbL films and PEG(Alk) -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.

Tailoring Layer-By-Layer Capsules for Biomedical Applications

“…As a result, the particles' circulation time is increased and untimely clearance out of the body is prevented (Figure 5). In all reported cases, the PEG-modified capsules have shown reduced protein adsorption, very low nonspecific binding to blood cells and were less efficiently taken up by macrophages [80,[93][94][95][96][97].…”

“…[76][77][78][79][80][81][82][83][84][85][86] PEG corona on capsules' surface Avoiding rapid clearance following in vivo administration…”

“…Disulfide crosslinked poly(vinylpyrrolidone) (PVPON)/PMA-based capsules released encapsulated molecules upon addition of a thiol-disulfide exchange reagent solution (dithiothreitol) [76][77][78]. Multilayer capsules consisting of PMA and alkyne-functionalized PEG or PVPON were generated by means of click chemistry using a bisazide linker [79,80]. These capsules were shown to disassemble under reducing conditions in vitro.…”

Bio‐Click Chemistry: Enzymatic Functionalization of PEGylated Capsules for Targeting Applications

“…Low-fouling materials such as poly(ethylene glycol) (PEG) and poly(Nvinyl pyrrolidone) (PVPON) are of interest for drug delivery as they exhibit a low level of nonspecific binding to cells. The capsules were assembled through hydrogen bonding by alternately layering alkyne-modified (1 %) PVPON (PVPON Alk ) [14] and poly(methacrylic acid) (PMA) on silica particles ( % 3 mm diameter), followed by deposition of alkyne-modified (5 %) PEG (PEG Alk ) [15] for PEGylation ( Figure 1). The alkyne groups of the multilayer film were then cross-linked with a bisazide linker [14] using alkyne-azide click chemistry.…”

Photoinducedin situformation of clickable PEG hydrogels and their antibody conjugation

“…[15,16] All these properties make azide-alkyne chemistry an elegant toolkit for the conjugation of proteins to polymers. Over the past few decades, hydrogels/ hydrophilic polymers have received significant interest because of their potential in areas such as pharmaceutics as drug carriers, [17][18][19][20] biology as cell [18,21] or biomolecular supporters, [22][23][24][25][26][27][28] chemistry as nano-reactors, [29][30][31] medicine as diagnostic devices [32][33][34] or scaffolds, [17,35,36] and biochemistry as solid supports. In particular, their hydrophilic nature makes them a highly biocompatible and distinct class of biomaterials perfectly suited for use in biomedical applications.…”