Thermoresponsive graphene oxide - Starch micro/nanohydrogel composite as biocompatible drug delivery system

Introduction: Stimuli-responsive hydrogels, which indicate a significant response to the environmental change (e.g., pH, temperature, light, ...), have potential applications for tissue engineering, drug delivery systems, cell therapy, artificial muscles, biosensors, etc. Among the temperature-responsive materials, poly (N-isopropylacrylamide) (PNIPAAm) based hydrogels have been widely developed and their properties can be easily tailored by manipulating the properties of the hydrogel and the composite material. Graphene oxide (GO), as a multifunctional and biocompatible nanosheet, can efficiently improve the mechanical strength and response rate of PNIPAAmbased hydrogels. Here, hydrogel composites (HCs) of PNIPAAm with GO was developed using the modified starch as a biodegradable cross-linker. Methods: Micro/nanohydrogel composites were synthesized by free radical polymerization of NIPAAm in the suspension of different feed ratio of GO using maleate-modified starch (St- MA) as cross-linker and Tetrakis (hydroxymethyl) phosphonium chloride (THPC) as a strong oxygen scavenger. The HCs were characterized by FT-IR, DSC, TGA, SEM, and DLS. Also, the phase transition, swelling/deswelling behavior, hemocompatibility and biocompatibility of the synthesized HCs were investigated. Results: The thermal stability, phase transition temperature and internal network crosslinking of HCs increases with increasing of the GO feed ratio. Also, the swelling/deswelling, hemolysis, and MTT assays studies confirmed that the HCs are a fast response, hemocompatible and biocompatible materials. Conclusion: The employed facile approach for the synthesis of HCs yields an intelligent material with great potential for biomedical applications.