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On-line Access: 2022-02-21

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Bio-Design and Manufacturing  2022 Vol.5 No.2 P.294-304

http://doi.org/10.1007/s42242-021-00175-y


4D printing of core–shell hydrogel capsules for smart controlled drug release


Author(s):  Shuo Zu, Zhihui Zhang, Qingping Liu, Zhenguo Wang, Zhengyi Song, Yunting Guo, Yuanzhu Xin & Shuang Zhang

Affiliation(s):  Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun 130025, China ; more

Corresponding email(s):   zhzh@jlu.edu.cn, liuqp@jlu.edu.cn

Key Words:  4D printing, Hydrogel capsules, Controlled release, Poly(N-isopropylacrylamide) (PNIPAM), Personalized drugs


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Shuo Zu, Zhihui Zhang, Qingping Liu, Zhenguo Wang, Zhengyi Song, Yunting Guo, Yuanzhu Xin & Shuang Zhang . 4D printing of core–shell hydrogel capsules for smart controlled drug release[J]. Journal of Zhejiang University Science D, 2022, 5(2): 294-304.

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Abstract: 
personalized drugs, as well as disease-specific and condition-dependent drug release, have been highly desired in drug delivery systems for effective and safe therapies. Four-dimensional (4D) printing, as a newly emerging technique to develop drug capsules, displays unique advantages that can autonomously control drug release according to the actual physiological circumstances. Herein, core–shell structured hydrogel capsules were developed using a multimaterial extrusion-based 4D printing method, which consists of a model drug as the core and UV cross-linked poly(N-isopropylacrylamide) (PNIPAM) hydrogel as the shell. Owing to the lower critical solution temperature (LCST)-induced shrinking/swelling properties, the prepared PNIPAM hydrogel capsules showed temperature-responsive drug release along with the topography changes in the cross-linked PNIPAM network. The in vitro drug release test confirmed that the PNIPAM hydrogel capsules can autonomously control their drug release behaviors according to changes in ambient temperature. Moreover, the increased shell thickness of these capsules causes an obvious reduction in drug release rate, distinctly indicating that the drug release behavior can be well adjusted by setting the shell thickness of the capsules. The proposed 4D printing strategy pioneers the paradigm of smart drug release by showing great potential in the smart controlled release of drugs and macromolecular active agents.

吉林大学张志辉、刘庆萍、祖硕等 | 4D打印用于药物智能控释的核壳型水凝胶胶囊

本研究论文聚焦4D打印用于药物智能控释的水凝胶胶囊。个性化药物,以及疾病特异性和条件依赖性药物释放在药物递送中一直备受追求。4D打印作为新兴的制造技术,在开发药物递送系统方面具有独特的优势,可以制造出根据生理条件(温度、pH值和离子等)智能控释的药物载体。在此,通过多材料挤出式4D打印方法开发了核壳型智能水凝胶胶囊,其内“核”为模型药物,其外“壳”为聚(N-异丙基丙烯酰胺)(PNIPAM)水凝胶。因PNIPAM具有最低临界溶液温度(LCST),所制备的PNIPAM水凝胶的内部孔隙尺寸会随温度的变化进行改变,这赋予了水凝胶胶囊温度响应释放的能力。体外药物释放研究表明,该水凝胶胶囊可以根据环境温度自主地改变其药物释放行为,并且还可以通过调整胶囊壳厚度对药物释放进行编程。所开发的4D打印水凝胶胶囊开创了智能释放的新范式,在药物和大分子活性物质的智能控释方面具有广阔的应用前景。

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