Comb-Type Grafted Hydrogels of PNIPAM and PDMAEMA with Reversed Network-Graft Architectures from Controlled Radical Polymerizations

Abstract

Dual thermo- and pH-responsive comb-type grafted hydrogels of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and poly(N-isopropylacrylamide) (PNIPAM) with reversed network-graft architectures were synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. Two kinds of macro-cross-linkers with two azido groups at one chain-end and different chain length [PNIPAM⁻(N₃)₂ and PDMAEMA⁻(N₃)₂] were prepared with N,N-di(β-azidoethyl) 2-halocarboxylamide as the ATRP initiator. Through RAFT copolymerization of DMAEMA or NIPAM with propargyl acrylate (ProA) using dibenzyltrithiocarbonate as a chain transfer agent, two network precursors with different content of alkynyl side-groups [P(DMAEMA-co-ProA) and P(NIPAM-co-ProA)] were obtained. The subsequent azido-alkynyl click reaction of macro-cross-linkers and network precursors led to the formation of the network-graft hydrogels. These dual stimulus-sensitive hydrogels exhibited rapid response, high swelling ratio and reproducible swelling/de-swelling cycles under different temperatures and pH values. The influences of cross-linkage density and network-graft architecture on the properties of the hydrogels were investigated. The release of ceftriaxone sodium from these hydrogels showed both thermal- and pH-dependence, suggesting the feasibility of these hydrogels as thermo- and pH-dependent drug release devices.

Keywords: ATRP; RAFT; click chemistry; hydrogels; network-graft architecture; stimuli-sensitive polymers.

Scheme 1

Schematic preparation of thermo- and pH-sensitive network-graft hydrogels of PNIPAM and PDMAEMA.

Figure 1

The ¹H-NMR spectra of AECPA (lower) and AEBIA (upper) in CDCl₃.

Figure 2

The ¹H-NMR spectra of PDMAEMA₆₀–(N₃)₂ (upper) and PNIPAM₆₀–(N₃)₂ (lower) in CDCl₃.

Figure 3

The ¹H-NMR spectra of P(DMAEMA-co-ProA) (upper) and P(NIPAM-co-ProA) (lower) in CDCl₃.

Figure 4

FT-IR spectra of network-graft hydrogels from P(DMAEMA-co-ProA) and PNIPAM₆₀–(N₃)₂.

Figure 5

Swelling-deswelling kinetics of n-N/g-D₆₀ (A) and n-D/g-N₆₀ (B) hydrogels in deionized water at 20 and 40 °C (pH = 7.0).

Figure 6

Swelling-deswelling kinetics of n-N/g-D₆₀ (A) and n-D/g-N₆₀ (B) hydrogels in deionized water at pH = 4.0 and 9.0 (20 °C).

Figure 7

Swelling-deswelling kinetics of n-N/g-D₆₀ (A) and n-D/g-N₆₀ (B) hydrogels in deionized water at pH = 4.0 and 9.0 (40 °C).

Figure 8

Drug release from n-N-5/g-D₆₀ (A and B), n-N-10/g-D₆₀ (C and D) and n-N-15/g-D₆₀ (E and F) hydrogels under different temperatures and pHs.