In this article, a sustained release formulation of the antioxidant gallic acid (GA) is presented in the form of glutathione responsive disulfide cross-linked poly(ethylene glycol)-based nanogels synthesized via aqueous inverse miniemulsion using atom transfer radical polymerization. The particle size was found to be in the range from 227 ± 51.78 to 573.3 ± 207.2 nm at three drug loading levels achieved i.e. 6.6, 14.26, and 18.29 wt.% of the nanogels with loading efficiency in the range of 60–70%. The release profile of the GA studied at three drug loading levels suggested a controlled release and the nanogels were capable of scavenging radicals and retained the antioxidant activity. The GA-loaded nanogels were found to be biocompatible on human cervical cancer cell lines (HeLa). DCFH-DA (2,7-dichlorofluorescin diacetate) assay evidenced that the nanogels were capable of scavenging the reactive oxygen species in cellular environment.

Ellagic acid (EA), a potential antioxidant phytochemical has low aqueous solubility and bioavailability. In this paper, encapsulation of ellagic acid has been carried out into the biodegradable disulfide crosslinked poly (ethylene glycol) PEO-based nanogels synthesized via AGET (activator generated electron transfer) ATRP (atom transfer radical polymerization), and their radical scavenging ability was evaluated. The encapsulation of the EA was carried out at two drug loading percentages, that is, 10 and 20 wt.% of the nanogels. 1,1-Diphenyl-2-picryldrazyl (DPPH) assay was utilized in order to assess the radical scavenging ability of the ellagic acid-loaded nanogels. A drug-loading level of about 2.5 wt.% was achieved with encapsulation efficiency of about 25% at 10 wt.% of the EA w.r.t nanogels, which was found to increase to about 4.7 wt.% with decreased encapsulation efficiency of 23.5% as EA content was increased to 20wt.% of the nanogels. Ellagic acid loading was found to be accompanied with increase in the size of the nanogels from144.6±39.52 nm for neat nanogels to217.8±105.5and633±160.1 nm at 2.5 and 4.7 wt.% drug loading level. The nanogels were found to be capable of scavenging radicals and biocompatible on human cervical cancer cell lines (HeLa cells) at appropriate concentrations.

The fabrication of novel and intelligent delivery systems that can effectively deliver therapeutics to the targeted site and release payload in enhanced/controlled manner is highly desired to overcome the multiple challenges in chemotherapy. The present article demonstrates the potential application of dual stimuli responsive nanogels as tumor microenvironment targeted drug delivery carrier. Disulfide cross-linked pH and redox responsive PEG-PDMAEMA nanogels were synthesized by atom transfer radical polymerization (ATRP). The nanogels were characterized by nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The PEG-PDMAEMA nanogels exhibited dual stimuli-responsive release of the encapsulated model anticancer drug (doxorubicin, DOX) due to the acidic pH-response of dimethyl amine group in PDMAEMA and reductive cleavage of the disulfide linkages. A relatively higher release of DOX was observed from the nanogels at pH 5.0 than at pH 7.4. DOX release was further accelerated in tumor simulated environment of pH 5.0 and 10 mM glutathione (GSH). Confocal microscopy images revealed that DOX-loaded PEG-PDMAEMA nanogels can rapidly internalize and effectively deliver the drug into the cells. The nanogels exhibited higher cytotoxicity in GSH-OEt pretreated HeLa cells than untreated cells. The dual stimuli responsive nanogels synthesized in this study exhibited many favorable traits, such as pH and redox dependent controlled release of drug, biodegradability, biocompatibility, and enhanced cytotoxicity, which endow them as a promising candidate for anticancer drug delivery.