Reduction-sensitive N, N'-Bis(acryloyl) cystinamide-polymerized Nanohydrogel as a Potential Nanocarrier for Paclitaxel Delivery

Linna Yu; Lingping Kong; Junpeng Xie; Wei Wang; Chen Chang; Hongli Che; Mingzhe Liu

doi:10.1080/15685551.2021.1914398

Reduction-sensitive N, N'-Bis(acryloyl) cystinamide-polymerized Nanohydrogel as a Potential Nanocarrier for Paclitaxel Delivery

Des Monomers Polym. 2021 Apr 18;24(1):98-105. doi: 10.1080/15685551.2021.1914398.

Authors

Linna Yu^{1

2

3}, Lingping Kong^{1

2

3}, Junpeng Xie^{1

2

3}, Wei Wang⁴, Chen Chang^{1

2

3}, Hongli Che^{1

2

3}, Mingzhe Liu^{1

2

3}

Affiliations

¹ Key Laboratory of Structure-Based Drugs Design & Discovery (Shenyang Pharmaceutical University) of Ministry of Education, Shenyang, P. R. China.
² Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, P. R. China.
³ Benxi Institute of Pharmaceutical Research, Shenyang Pharmaceutical University, Benxi, P. R. China.
⁴ Precedo Pharmaceuticals Co. Ltd., Hefei, P. R. China.

Abstract

Novel monomer, N, N'-bis(acryloyl) cystinamide (NBACA), was designed and synthesized with L-cystine as row material. By using this NBACA both as the monomer and crosslinker, reduction-sensitive nanohydrogel was prepared in ethanol via distillation-precipitation polymerization. The obtained nanohydrogel can provide a relatively hydrophobic environment and hydrogen-bonding sites inside the gel; therefore, it is suitable for loading hydrophobic drug. When paclitaxel that possess poor water-solubility was used as a model drug, the nanohydrogel represented a high drug-loading capacity, and dispersed well in aqueous solutions. Furthermore, the disulfide-group-containing nanohydrogel exhibited good reduction-sensitive drug-release behavior. The nanohydrogel biodegraded rapidly in a reducing environment, and released approximately 80% of the PTX within 24 h. Cytotoxicity assays showed that the PTX-loaded nanohydrogel exhibited high cytotoxicity against MCF-7 breast cancer cells, while blank nanohydrogels displayed a negligible cytotoxicity.

Keywords: Paclitaxel; biomaterials; drug delivery; nanohydrogel; redox stimuli.

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 21875145] and the Liaoning Provincial Natural Science Foundation of China [grant number 20180550392].