Redox/pH stimuli-responsive biodegradable PEGylated P(MAA/BACy) nanohydrogels for controlled releasing of anticancer drugs

Stimuli responsive drug delivery systems have attracted considerable attention due to their ability to deliver drugs on demand to special tissues and cells (e.g. cancer cells). In this paper, we fabricated a new kind of redox/pH dual stimuli-responsive biodegradable poly(methacrylic acid) (MAA) nanohydrogels crosslinked by N,N-bis(acryloyl)cystamine (BACy) through a facile reflux-precipitation polymerization. Subsequently polyethylene glycol (PEG) was grafted onto the surface of nanohydrogels to improve their long circulation time. This kind of PEGylated nanohydrogels could be degraded into short linear polymer chains in the solution of 10 mM glutathione (GSH) due to the sensitive disulfide bonds in the cross-linked networks. Interestingly, we found that the hydrophilic PEGylated nanohydrogels could be simultaneously loaded with hydrophilic drug doxorubicin (DOX) and hydrophobic drug paclitaxel (PTX) with high drug loading efficiency because of its regional hydrophobic nature in the nanohydrogels. The cumulative release profile showed that either lower pH (5.0) or reducing environment (GSH) or a combination could significantly accelerate the drug release from the drug-loaded nanohydrogels. In addition, the experimental results on living cells indicated that the multi-drug-loaded system had synergistic effect on cancer therapy. (C) 2015 Elsevier B.V. All rights reserved.