Nitrite-Responsive Hydrogel: Smart Drug Release Depending on the Severity of the Nitric Oxide-Related Disease
Jialiang Xiong, Ruoxiao Xie, Yu Wang, Chenlong Wang, Yongjian Ai, Wen-Chen Zheng, Mingyu Ding, Jianyi Gao, Jiaping Wang, Qionglin Liang
Abstract
Nitric oxide (NO) is known as one of the most important biomarkers of many diseases. However, the development of NO-triggered drug releasing platforms is challenging due to the low concentration and short lifetime of NO in vivo. In this work, a novel nitrite (NO2–)-responsive hydrogel (DHPL-GEL), which can be used for smart drug release depending on the severity of the NO-related disease, is demonstrated. A dihydropyridine cross-linking agent is designed to construct DHPL-GEL to enable the responsive degradation of the hydrogel triggered by NO2–. On-demand release of the drug loaded in DHPL-GEL was observed under the stimulation of various concentrations of NO2– at the physiological level both in vitro and in vivo. In the inflammatory arthritis rat model, the DHPL-GEL drug delivery system showed a better therapeutic effect and less side effects than the traditional therapy and nonresponsive hydrogel drug delivery system, demonstrating the promising application of the NO2–-responsive hydrogel for the treatment of NO-related diseases.