Injectable hydrogels with multistimuli responsiveness to electrical field and pH as a drug delivery system have been rarely reported. Herein, we developed a series of injectable conductive hydrogels as “smart” drug carrier with the properties of electro-responsiveness, pH-sensitivity, and inherent antibacterial activity. The hydrogels were prepared by mixing chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD) as a cross-linker. The chemical structures, morphologies, electrochemical property, swelling ratio, conductivity, rheological property, in vitro and in vivo biodegradation, and gelation time of hydrogels were characterized. The pH-responsive behavior was verified by drug release from hydrogels in PBS solutions with different pH values (pH = 7.4 or 5.5) in an in vitro model. As drug carriers with electric-driven release, the release rate of the model drugs amoxicillin and ibuprofen loaded within CP/OD hydrogels dramatically increased when an increase in voltage was applied. Both chitosan and polyaniline with inherent antibacterial properties endowed the hydrogels with excellent antibacterial properties. Furthermore, cytotoxicity tests of the hydrogels using L929 cells confirmed their good cytocompatibility. The in vivo biocompatibility of the hydrogels was verified by H&E staining. Together, all these results suggest that these injectable pH-sensitive conductive hydrogels with antibacterial activity could be ideal candidates as smart drug delivery vehicles for precise doses of medicine to meet practical demand.

Statement of Significance

Stimuli-responsive or “smart”hydrogels have caused great attention in the field of biotechnology and biomedicine, especially on designing novel drug delivery systems. Compared with traditional implantable electronic delivery devices, the injectable hydrogels with electrical stimuli not only are easy to generate and control electrical field, but also they could avoid frequent invasive surgeries which offer a new avenue for chronic diseases. In addition, designing a drug carrier with pH-sensitive property could release drug efficiently in targeted acid environment and it could reinforce the precise doses of medicine. Furthermore, caused by opportunistic microorganisms and rapid spread of antibiotic-resistant microbes, infection is still a serious threat for many clinical utilities. To overcome these barriers, we designed a series of injectable antibacterial conductive hydrogels based on chitosan-graft-polyaniline (CP) copolymer and oxidized dextran (OD), and demonstrated their potential as “smart” delivery vehicles with electric field and pH-responsive properties for triggered and localized release of drugs.

中文翻译：

---

可注射的抗菌导电水凝胶，对电场和pH具有双重响应，可实现局部“智能”药物释放

很少有对电场和pH具有多重刺激响应的可注射水凝胶作为药物输送系统的报道。本文中，我们开发了一系列可注射的导电水凝胶，作为“智能”药物载体，具有电响应性，pH敏感性和固有的抗菌活性。通过混合壳聚糖-接枝-聚苯胺（CP）共聚物和氧化葡聚糖（OD）作为交联剂来制备水凝胶。的化学结构，形态，电化学性能，溶胀比，导电性，流变性，在体外和体内生物降解，和水凝胶的凝胶化时间进行表征。通过在不同pH值（pH = 7.4或5.5）的PBS溶液中从水凝胶中释放药物来验证pH响应行为。体外模型。作为具有电动释放的药物载体，当施加电压时，装载在CP / OD水凝胶中的模型药物阿莫西林和布洛芬的释放速率显着增加。壳聚糖和聚苯胺均具有固有的抗菌性能，使水凝胶具有出色的抗菌性能。此外，使用L929细胞对水凝胶的细胞毒性测试证实了它们良好的细胞相容性。在体内的水凝胶的生物相容性是由H＆E染色验证。总之，所有这些结果表明，这些具有抗菌活性的可注射pH敏感的导电水凝胶可作为理想的候选药物，作为智能药物递送工具，用于精确剂量的药物以满足实际需求。

重要声明

刺激响应或“智能”水凝胶在生物技术和生物医学领域引起了极大的关注，特别是在设计新型药物递送系统方面。与传统的植入式电子输送装置相比，具有电刺激的可注射水凝胶不仅易于产生和控制电场，而且还可以避免频繁的侵入性手术，这为慢性疾病提供了新的途径。此外，设计具有pH敏感特性的药物载体可以在目标酸性环境中有效地释放药物，并且可以增强精确剂量的药物。此外，由于机会微生物和抗生素抗性微生物的迅速传播，感染仍然是许多临床应用的严重威胁。为了克服这些障碍，