Redox-degradable microgel based on poly(acrylic acid) as drug-carrier with very high drug-loading capacity and decreased toxicity against healthy cells
2021
Abstract In this paper we report on synthesis of pH sensitive and degradable microgel for a high-capacity doxorubicin-drug carrier. Microgel was based on poly(acrylic acid) cross-linked with a redox-sensitive linker - N,N’-bis(acryloyl)cystamine, and was synthesized by using the distillation polymerization. Highly monodispersed spherical particles were obtained. The presence of carboxylic groups in the chains gave pH-sensitivity to the microgel; as a result the microgel size changed after a change in pH. The presence of disulfide bridges in the microgels gave them the ability to degrade. The extent of degradation of the microgel was examined by using the dynamic light scattering technique and electron microscopy. The degradation of the microgel was caused by the reduction of -S-S- bridges by glutathione. At the beginning of the degradation process the swelling of the microgel particles was observed because only a part of disulfide bonds were broken. The break of the remaining -S-S- bonds led to the complete degradation of the microgel. The fact that the microgel consisted mainly of the carboxylic groups allowed us to bind a high amount of the anticancer drug. Under the conditions typical for cancer cells, i.e. at pH 5 and in the presence of increased concentration of glutathione, the highest amount of doxorubicin could be released. The MTT assay indicated that compared to free doxorubicin the microgel particles loaded with doxorubicin were more cytotoxic against the MCF-7 breast cancer cells, while they were 27 times less toxic against the MCF-10A healthy cells.
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