Clickable Poly(2-oxazoline) Architectures for the Fabrication of Low-Fouling Polymer Capsules

Abstract

Hollow polymer capsules were prepared from linear as well as brush-like poly(2-oxazoline)s (POxs). Linear POxs containing alkene functionalities were obtained by cationic ring-opening polymerization (CROP), whereas the brush POxs bearing alkyne moieties were synthesized by a combination of CROP and reversible addition fragmentation chain transfer (RAFT) polymerization. Multilayers consisting of POx/poly(methacrylic acid) (PMA) were sequentially deposited onto silica particle templates and the films were stabilized either by thiol-ene (TE) chemistry or copper-catalyzed azidealkyne cycloaddition (CuAAc). Stable, monodisperse capsules were formed after removal of the silica particles with hydrofluoric acid, and were observed using fluorescence and atomic force microscopy (AFM). Both architectures exhibited lowfouling behavior, an essential criteria for therapeutic carriers to be utilized in bioapplications. In particular, the brush-like POx capsules show potential as a viable alternative material for the fabrication of low-fouling capsules.

Covalently cross-linked poly(2-oxazoline) materials for biomedical applications – from hydrogels to self-assembled and templated structures

“…poly(ethylene glycol), and poly(Nvinylpyrrolidone)) and donors (e.g. 95 After (POx/PMAA) multilayer assembly onto silica particle templates, the films were stabilized by thiol-ene chemistry (linear POx) or copper-catalyzed azide-alkyne cycloaddition (brush-like POx) and the template was removed by hydrofluoric acid. 91 However, the pH range in which stable films can be formed is limited and depends on the pK a of the polymers and the interaction between the hydrogen bonding pair.…”

Poly(2-oxazoline)s and click chemistry: A versatile toolbox toward multi-functional polymers

“…Other PAOx-based microparticles, for which click chemistry has been applied to cross-link side-chain functionalized linear PAOx, are hollow capsules that can be used in drug delivery applications. 67 These capsules were synthesized by layer-by-layer assembly of PAOx/poly(methacrylic acid) brush copolymers onto silica particle templates, which were etched away with HF. Investigation of the protein adsorption showed low fouling behavior, although the best results were obtained for brush-like capsules based on a oligo(2-ethyl-2-oxazoline)methacrylate macromonomer with cross-linkable oligoethyleneglycol moieties.…”

Recent developments in multilayered polymeric particles – from fabrication techniques to therapeutic formulations

“…101 It was shown that capsules prepared from brush-like POx exhibit low-fouling properties. H-bonded assembled films are of particular interest because they can be designed to be responsive under biologically relevant conditions.…”

“…H-bonded assembled films are of particular interest because they can be designed to be responsive under biologically relevant conditions. 101 In another study by Kempe et al, synthesis of brush-like poly(2-ethyl-2-oxazoline) (PEtOx) with pendant thiol moieties and the fabrication of redox-responsive LbL-assembled PEtOx capsules were reported (Scheme 6). Low-fouling coatings decrease or resist nonspecific protein adsorption, which is a crucial property of advanced polymer carriers because they can allow efficient cargo delivery to a targeted site.…”