A two-dimensional g-C₃N₄ nanosheet for high loading and sustained release of water-soluble drug salvianolic acid B

Delivering water-soluble drugs via carriers often causes problems such as low loading and rapid releasing, so it is an urgent need to construct a high-load sustained-release drug delivery system for the clinical application of water-soluble drugs. Two-dimensional layered nanomaterials exhibit great potential in drug delivery due to their high specific surface area. In this study, bulk graphitic carbon nitride (b-g-C₃N₄) was obtained by calcination of urea. Graphitic carbon nitride nanosheets (g-C₃N₄-NS) were made from an alkali chemical-ultrasonic-assisted stripping process. Scanning electron microscopy, transmission electron microscopy and atomic force microscopy were adopted to observe the morphological characteristics of g-C₃N₄-NS, while the structural characteristics of g-C₃N₄-NS were analyzed by X-ray diffractometer and Fourier transform infrared spectroscopy. Ultraviolet spectrometry and fluorescence spectrometry were used to investigate the optical properties of g-C₃N₄-NS, and scanning electron microscopy and X-ray diffractometer were employed to investigate the stability of g-C₃N₄-NS. Polyethyleneimine (PEI) was applied in the study to functionally modify g-C₃N₄-NS, and salvianolic acid B (Sal B) was used as a water-soluble drug model to investigate the loading capacity and drug releasing behavior of g-C₃N₄-NS. The results showed that g-C₃N₄-NS had a sheet structure, and it is easy to self-assemble in layers in the ionic environment to create flocculating settling. PEI modification can lead to the switching in the surface charge of g-C₃N₄-NS and significantly improve its stability. The results of cytotoxicity test and zebrafish embryo toxicity test showed that the toxicity was low when the concentration of PEI-g-C₃N₄-NS was less than 800 μg·mL^-1. The large specific surface area and surface charge of PEI-g-C₃N₄-NS allow the maximum load factor over Sal B to reach 327.4%. In addition, PEI-g-C₃N₄-NS can continuously release drugs slowly, with a cumulative release rate of 79.2% in seven straight days. The release process conforms to the Higuchi equation. In summary, g-C₃N₄-NS modified by PEI exhibits good biocompatibility and high stability, and shows great potential in high-load and sustained-release applications of water-soluble drugs.