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 PNIPAAm-based 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.