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RESEARCH PRODUCT

Incorporation of dynamic boronate links and Ag nanoparticles into PVA hydrogels for pH-Regulated and prolonged release of methotrexate

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Abstract In this study, pH-responsive hydrogels based on PVA-boronate crosslinks were prepared via a simple route and used for controlled and targeted delivery of anticancer drug methotrexate. A double network (DN) hydrogel composed of didiol-boronate/PVA complex as the first network and PVA crystallites generated by a freeze-thaw process as the second one was developed. The swelling of PVA-boronate DN hydrogels demonstrated high sensitivity to multiple stimuli including the pH, temperature, and ionic strength of the media thanks to the dynamic boronate links in the first network. Moreover, unlike previously reported hydrogels based on the boronate linkages, the new DN hydrogels preserved their structural stability in acidic media due to the second network and consequently, a sustained drug release was achieved under low pH conditions. Methotrexate release from the hydrogels at pH 5.4 was faster and greater than that at pH 7.4, agreeing with the gels’ swelling behavior under the two pH conditions. Interestingly, with the incorporation of Ag nanoparticles (NPs) for the antibacterial function, PVA-boronate hydrogels showed not only a higher pH responsiveness in drug release but also a more sustained process. These hydrogels can be considered in prolonged cancer therapy with reduced side effects.