Poly[N-(2-hydroxypropyl)methacrylamide] nanogels by RAFT polymerization in inverse emulsion†
Inverse emulsion reversible addition-–fragmentation chain transfer (RAFT) polymerization has been used to generate N-(2-hydroxypropyl)methacrylamide (HPMA) based nanoparticles and reduction-sensitive nanogels with diameters of 100–200 nm. Inverse emulsion RAFT homopolymerization of HPMA afforded nanoparticles composed of linear PHPMA macromolecules with relatively narrow molecular weight distributions (Mw/Mn = 1.35–1.55). Copolymerization of HPMA with N,N′-bis(acryloyl)cystamine (BAC) at BAC to chain transfer agent ratios >1.5 resulted in crosslinked nanoparticles that could be isolated and redispersed in water. At smaller BAC to chain transfer agent ratios, non-crosslinked nanoparticles composed of (hyper)branched poly(N-(2-hydroxypropyl)methacrylamide-co-N,N′-bis(acryloyl)cystamine) copolymers were obtained. Addition of protein to the aqueous phase during the inverse emulsion copolymerization of HPMA and BAC allowed preparation of stimuli-responsive, protein-loaded nanogels, which were shown to release their payload under reductive conditions, e.g. upon exposure to tris(2-carboxyethyl)phosphine hydrochloride. These reduction-sensitive nanogels are of interest, e.g. as carriers for the delivery of proteins.