Reversibly Switchable pH‐ and Thermoresponsive Core–Shell Nanogels Based on Poly(NiPAAm)‐graft‐poly(2‐carboxyethyl‐2‐oxazoline)s

Abstract

Amphiphilic graft copolymers with a thermosensitive PNiPAAm backbone and pH-sensitive hydrophilic poly(2-carboxyethyl-2-oxazoline) graft chains are synthesized. In aqueous solution, stable micelle-like aggregates are formed by increasing the temperature in the pH range 4.5-5.5. The micelles are crosslinked by electron-beam irradiation, yielding stable core-shell nanogels of about 100 nm diameter with reversible thermoand pH-dependent swelling behavior. The temperature sensitivity is provided by a conformational change in the PNiPAAm core, whereas the thickness of the poly(2-carboxyethyl-2-oxazoline) corona depends on pH. The reversible bisensitivity of core-crosslinked nanogels is verifi ed by DLS, while AFM measurements demonstrate the predicted core-shell structures of the aggregates. other sensitivities, that is, pH, light, magnetic fi eld, solvent quality, etc., and their effects on the reversible self-assembly in aqueous solutions or on hydrogel organization.Poly( N -isopropylacrylamide) (PNiPAAm) is the most frequently studied thermosensitive polymer and shows a phase transition in aqueous solutions at a physiological interesting temperature range. [ 2 ] The formation of PNiPAAm-based block copolymers with pH-responsive poly(acrylic acid) (PAA) [ 3 ] or poly( N -acryloylpyrrolidine) [ 1 , 4 ] offered new self-assembly possibilities. In dependence on the applied temperature and pH value, the PNiPAAmblock -PAA copolymers change their hydrophobic and hydrophilic balance and form different types of micelles. [ 3 ] Also random PNiPAAm-co -PAA and PAA-graft -PNiPAAm structures were realized by Chen and Hoffman, [ 5 ] and the temperature-induced phase transition over a wide range of pH values could be demonstrated. Topp et al. [ 6 ] reported on the synthesis of block copolymers of types A-B and A-B-A composed of poly(ethylene glycol) (PEG) and PNiPAAm as well as their micellization behavior. The design of these copolymers is based on the hydrophobic character of PNiPAAm above its lower critical solution temperature 4 5 6 7 8 9 1 0 30 35 40 45 50 55 60 R h (nm) pH 59 nm 44 nm 47 nm 34 nm Δ Δ Δ ΔT 25 °C 50 °C 12 % 100 % Degree of dissociation Δ Δ Δ ΔT

Thermal Properties of Methyl Ester-Containing Poly(2-oxazoline)s

“…Moreover, the ester can be hydrolyzed to the corresponding carboxylic acid providing a versatile handle for conjugation as well as a means to introduce pH responsiveness. Although the potential of side-chain methyl ester-containing PAOx copolymers is well established, there is remarkably little known about their thermal features and thermoresponsive behavior [33,[43][44][45][46][47].…”

Design Strategies for Functionalized Poly(2-oxazoline)s and Derived Materials

“…An increasing quantity of chloromethylstyrene in the backbone lowered the LCST, while an increasing content of pMeOx or pEtOx (relative to the backbone) raised the transition temperature. Voit et al employed the random copolymer composed of N-isopropylacrylamide and chloromethylstyrene, which they used as macroinitiator for the graft polymerization of (ester) n PrOx (the chloromethylstyrene units acted as initiators after dissociation of the chloride anions) [105]. In solution, core-shell nanogels with micellar shape and reproducible thermo-and pH-dependent swelling behavior formed, which could be stabilized by electron-beam crosslinking.…”

Synthesis and characterization of new pH- and thermo-responsive hydrogels based on N-isopropylacrylamide and 2-oxazolines

“…[18] The iodomethylstyrene initiates the polymerization of MEtOxa and MeOxa, and because the reactivity of these monomers is similar [21][22][23] finally a statistical copolymer of these monomers is formed which contains a vinyl group at the one chain end (starting group) and a OH group at the other chain end, because the polymerization has been terminated by KOH in methanol. [32] The structure of MM was confirmed by 1 H NMR spectroscopy.…”

“…[10,11] Some polyoxazolines, as polymethyloxazoline, have hydrophilic character while others, as for example polynonyloxazoline, have hydrophobic character. In recent years, our research group has developed, based on NiPAAm and 2-oxazolines, different polymer structures soluble in water and sensitive to temperature and pH, [20][21][22][23] which formed stable and reversible micelles, and the formation of double-responsive nanogels by irradiation with electrons was demonstrated.…”