Molecular dynamics study on the encapsulation and release of anti-cancer drug doxorubicin by chitosan

Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but it has certain limitations in its therapeutic effects due to poor tumor selectivity. Chitosan-based pH-sensitive polymers drug delivery systems could improve DOX's activity and selectivity against tumor cells. Understanding the atomic interaction mechanism between chitosan and DOX at different pH levels is important in the design and application of chitosan-based drug delivery systems. In this study, molecular dynamics simulations were performed to investigate the encapsulation and release of DOX by chitosan at different pH levels. Our results show that the protonation state of amine groups of chitosan and the p-p stacking interaction between the conjugated anthraquinone ring of DOX regulate the interaction behavior between chitosan and DOX. Moreover, DOX could gradually release from chitosan at acidic pH environment in tumor tissue. These results revealed the underlying atomic interaction mechanism between DOX and chitosan at various pH levels and may provide novel ideas for the design and application of chitosan-based drug delivery system.