Molecular interaction mechanisms of glycol chitosan self-healing hydrogel as a drug delivery system for gemcitabine and doxorubicin

Glycol chitosan is a derivative of chitosan that has attracted attention in recent years due to its biocompatibility and biodegradability. Due to its unique biological characteristics, it has been widely used in hydrogels and biomaterials. In this study, we explored the loading efficiency of a self-healing hydrogel (GC-DP) comprising glycol chitosan (GC) and telechelic difunctional poly(ethylene glycol) (DF-PEG) for delivering the anticancer drugs gemcitabine and doxorubicin through full atomistic simulations. We also constructed full atomistic models of the two drug delivery systems at three drug concentrations of 10%, 40%, and 80% to understand how the drug concentration affects the loading efficiency and molecular structure of the GC-DP hydrogels. Through the analysis of the results, we show that the GC-DP hydrogel exhibits excellent loading efficiency for both gemcitabine and doxorubicin at all drug concentrations (10%, 40% and 80%). Our results reveal that the main mechanism of interaction between the GC-DP hydrogels and gemcitabine is van der Waals adsorption and that the dominant interactions between the GC-DP hydrogel and doxorubicin are hydrogen bonds for the D10 model and van der Waals adsorption for the D40 and D80 models. Our results provide molecular insights into how drug molecules are carried by hydrogel materials and indicate that the GC-DP hydrogel is a promising candidate for carrying both gemcitabine and doxorubicin, and thus serving as a novel drug carrier for cancer treatment.