Fabrication of methacrylated casein/alginate microspheres crosslinked by UV light coupled with Ca 2+ chelation for pH-sensitive drug delivery

Casein serves as a protein extract from cow milk and its products; it is an available and cheap natural polymer material. Casein-based hydrogels have been extensively used in drug delivery systems due to their good biocompatibility and fast degradation. Although chemical crosslinking agents have been used for crosslinking of casein hydrogels, it is also associated with adverse effects and potential biotoxicity. In this work, casein was modified with methacrylic anhydride (MA). The functionalized casein (CaseinMA) possessed the ability to form hydrogels under 365 nm UV light in water solution without using toxic agents. Alginate was (0.4%, 0.8%, and 1.2%) found to successfully adjust the mechanical performance of CaseinMA hydrogels. The swelling property and degradation behavior indicated that the composite hydrogels had excellent water holding ability and degradability. MTT assay and hemolytic test demonstrated that CaseinMA/Alg hydrogels containing photoinitiator (Irgacure 2959) had good biocompatibility. At last, CaseinMA/Alg microspheres loaded with metformin hydrochloride (MET) were fabricated by using electrostatic droplet technology. The CaseinMA/Alg microspheres had a pH-sensitive property and slow sustained release as compared to mono-component microspheres in drug releasing test. CaseinMA/Alg hydrogels were confirmed that had good biocompatibility and mechanical properties; it is expected to be applied in many fields such as drug delivery system and wound management. Graphical abstract