Multi salt strategy based on curcumin pyrimidine derivatives prodrugs: Synthesis, biological activity, in vitro and in vivo imaging, and drug distribution research

Herein, a feasible strategy to enhance the water solubility of potential anti-tumor drugs was utilized, which was to combine hydrochloric acid or sulfuric acid into its molecules. In order to increase drug targeting, three different types of Eudragit® (stomach soluble, enteric soluble and permeable) was used to encapsulate these two salt under mild reaction conditions to obtain six kinds of nano polymer complexes. In order to simulate the gastrointestinal environment, spectroscopic tests were conducted on nanoparticles in PBS buffer solutions with different pH values. The micromorphology of the six complexes was analyzed by TEM. The results showed that the potential drugs were uniformly dispersed in the drug carrier materials, and the particle size was 100–500 nm. The Zeta potential test showed that the complexes had positive stability. The confocal microscope imaging experiments were carried out in different channels of HCT-116 and LO2 cells. The results showed that the complexes had favorable biocompatibility and imaging properties. The calculation of Pearson coefficient showed that some complexes could enter the nucleus. The cell proliferation toxicity test (CCK8) experiment and the TEM experiment of cell uptake localization showed that the complex had definite anti-tumor activity and low cytotoxicity, and the distribution of the complexes was detected in the nucleus and cytoplasm. In vivo imaging experiment, strong fluorescence intensity of the compounds was detected in the subcutaneous tumor tissue of mice. The release of six compounds had the potential of slow and controlled release, and could be well targeted to the stomach of mice. Therefore, potential salt curcumin derivatives are ideal potential anti-tumor prodrugs, and the resulting nanoparticles are suitable for delivery in organisms.