Theoretical Investigation of Chitosan-Assisted Controlled Release of Digestive System Antitumor Drug Fluorouracil.

5-Fluorouracil (5-FU) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. However, due to poor tumor selectivity, 5-FU's therapeutic effect has certain limitations. 5-FU's activity and selectivity against tumor cells can be improved by chitosan assisted drug delivery systems. Understanding the atomic interaction mechanism between chitosan and 5-FU is important. In this work, the interactions between 5-FU and different types of chitosan were systematically investigated by using molecular dynamics (MD) simulation. Based on the radial distribution function and the free energy calculation, our results demonstrate that the functional groups of chitosan could greatly regulate the interaction behavior between chitosan and 5-FU. Moreover, 5-FU could gradually release from chitosan at a more acidic pH (tumor tissues) environment. These results revealed the underlying atomic interaction mechanism between 5-FU and chitosan at various pH levels, and may be helpful in the design of chitosan-based drug delivery systems.