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Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery

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Abstract

Hydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems (DDS). However, it remains challenging to engineer hydrogels that specifically respond to externally applied mechanical forces with minimal basal drug leakage under normal stressful physiological conditions. Here we present an ultrasound responsive hydrogel-based DDS with special dual-crosslinked nanoscale network architecture. The covalent crosslinks endow the hydrogel high mechanical stability and greatly suppress deformation-triggered drug release. Meanwhile, the dynamic covalent boronate ester linkages between hydrogel backbone and the anti-inflammation compound, tannic acid (TA), allow effective ultrasound-triggered pulsatile release of TA. As such, the hydrogel shows distinct drug release profiles under compression and ultrasound. A proof-of-principle demonstration of the suppression of inflammation activation of macrophage upon ultrasound-triggered release of TA was also illustrated. We anticipate that this novel hydrogel-based drug delivery system can be used for the treatment of inflammatory diseases on load-bearing tissues, such as muscle and cartilage.

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Acknowledgements

This research is supported mainly by the National Natural Science Foundation of China (Nos. 21522402, 11674153, 81622033 and 21774057) and the Fundamental Research Funds for the Central Universities (No. 020414380080).

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Author notes

  1. Wenxu Sun, Heting Jiang, and Xin Wu contributed equally to this work.

Authors and Affiliations

  1. Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing, 210093, China

    Wenxu Sun, Heting Jiang, Xin Wu, Zhengyu Xu, Juan Wang, Meng Qin, Wei Wang & Yi Cao

  2. Department of Sports Medicine and Adult Reconstructive surgery, Drum Tower Hospital; Medical School, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210008, China

    Chen Yao, Qing Jiang & Dongquan Shi

  3. Joint Research Center for Bone and Joint Disease, Model Animal Research Center (MARC), School of Chemistry and Chemical Engineering, and State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210093, China

    Chen Yao, Qing Jiang & Dongquan Shi

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  1. Wenxu Sun
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Correspondence to Wei Wang, Dongquan Shi or Yi Cao.

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Sun, W., Jiang, H., Wu, X. et al. Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery. Nano Res. 12, 115–119 (2019). https://doi.org/10.1007/s12274-018-2188-4

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