Polymerisation-induced self-assembly-derived nanogels for the preparation of polymer/nanoparticle complex coacervate hydrogels

Abstract

Reversible addition-fragmentation chain transfer (RAFT) polymerisation was used to prepare various anionic, sterically stabilised diblock copolymer nanoparticles via polymerisation-induced self-assembly (PISA). These nanoparticles (NPs) were then evaluated as putative nanosized crosslinkers to prepare polymer nanoparticle-based complex coacervate (PNCC) hydrogels via mixing with cationic branched polyethyleneimine (bPEI). Firstly, RAFT aqueous emulsion polymerisation of a statistical copolymer of benzyl methacrylate (BzMA) and methacrylic acid (MAA) was conducted at pH 2, 70 °C using anionic poly(3-sulfopropyl methacrylate) (PKSPMA68) as a water-soluble precursor block. Thus, pH-responsive NPs comprising a hydrophobic polyacid core-forming block and a sulfonate-functional stabiliser block were formed. With the introduction of methacrylic acid into the core of the NPs, they become swollen with increasing pH, indicating nanogel-type behaviour. PNCC hydrogels were prepared by simply mixing the PISA-derived nanogels and cationic branched polyethyleneimine (bPEI) at 20% w/w. In the absence of MAA in the core of the NPs, gel formation was not observed. The mass ratio between nanogels and bPEI affected hydrogel strength and a mixture of bPEI and PKSPMA68-P(BzMA0.6-stat-MAA0.4)300 NPs with a mass ratio of 0.14 at pH ~7 resulted in a hydrogel with a storage modulus of approximately 2000 Pa, as determined by oscillatory rheology. This PNCC hydrogel was shear-thinning and injectable, with recovery of gel strength occurring rapidly after the removal of shear. Subsequently, it was demonstrated for the first time that colloidal nanogels formed from a pH-responsive poly(succinate)-functional core and a poly(sulfonate)-functional corona can be prepared via a RAFT-mediated aqueous emulsion PISA route. Specifically, a PKSPMA50 macromolecular chain-transfer agent (macro-CTA) was synthesised via RAFT solution polymerisation followed by chain-extension with a hydrophobic, carboxylic acid-functional, 2-(methacryloyloxy) ethyl succinate (MES) monomer at pH 2. Colloidal NPs with tunable diameters between 66 to 150 nm, depending on the core composition, and narrow particle size distributions were obtained at 20% w/w solids. Well-defined pH-responsive nanogels that swell on increasing the pH could be prepared even without the addition of a cross-linking comonomer and introducing an additional cross-linker to the core led to smaller nanogels with lower swelling ratios. These nanogels could reversibly change in size on cycling the pH between acidic and basic conditions and remain colloidally stable over a wide pH range and at 70 °C. Follow-up studies examined PKSPMA58-PMES500 nanogels as nanosized, anionic crosslinkers for the preparation of PNCC hydrogels using bPEI at 20% w/w solids. The PKSPMA58-PMES500 nanogels form weak hydrogels upon swelling at 20% w/w. But adding bPEI can improve gel properties through the formation of PNCCs. The effect of varying pH of the bPEI/PKSPMA58-PMES500 mixture and bPEI-to-nanogel mass ratio on the formation of PNCC hydrogels was examined. At pH 3, only phase separated mixtures were produced comprising a paste-like condense phase and an aqueous dilute phase. At pH 7.5, gelation occurred on the addition of bPEI in a narrow MR range (0 ≤ MR ≤ 0.1), and phase separation occurred with additional bPEI. At pH 9, on the addition of bPEI gelation occurred over a wide MR range (0 ≤ MR ≤ 1.9) and the mixture became free-flowing with additional bPEI. At pH 11, gelation occurred after 24 h with a MR 0.2. All bPEI/PKSPMA58-PMES500 PNCC hydrogels had improved elasticity in comparison to bPEI/PKSPMA68-P(BzMA0.6-stat-MAA0.4)300 PNCC hydrogels. A maximum gel strength of 1300 Pa was obtained for bPEI/PKSPMA58-PMES500 PNCC hydrogels prepared at pH 9 with a MR 0.1. Shear-thinning behaviour was observed for all bPEI/PKSPMA58-PMES500 PNCC hydrogels. However, after the removal of shear the recovery efficiency of bPEI/PKSPMA58-PMES500

Date of Award	31 Dec 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Brian Saunders (Supervisor) & Lee Fielding (Supervisor)