Injectable antibacterial conductive hydrogels with dual response to an electric field and pH for localized "smart" drug release.

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 attracted 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 could avoid frequent invasive surgeries that 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 we demonstrated their potential as "smart" delivery vehicles with electro-responsiveness and pH-responsive properties for triggered and localized release of drugs.