Molecular dynamics study on the interaction between doxorubicin and hydrophobically modified chitosan oligosaccharide

Doxorubicin (DOX) is a broad spectrum anti-tumor anthracycline antibiotic used in cancer chemotherapy, but it has certain limitations in its therapeutic effects due to non-specific targeting. Amphiphilic polymeric micelle drug delivery systems could help to improve the activity and selectivity of DOX against tumor cells. In this study, molecular dynamics simulations were performed to investigate the interaction between DOX and ten hydrophobic acid modified chitosan oligosaccharides (COS). The pi-pi interactions in the systems with aromaticity have been found to contribute to a great part of the van der Waals interactions and play a significant role in the DOX loading process. The encapsulation of DOX by long-chain fatty acid-grafted COS mainly depends on a high binding strength and sandwiched configuration, where the hydrophobic interactions are essential to the encapsulation process. The solvent structure around DOX and the grafted COS was found to have a relationship with the way DOX and drug carrier bind to each other. Moreover, the results derived by our computational model were compared to the experimental data obtained in our lab and the data available in the literature. It was found that the interaction strength between DOX and hydrophobically modified COS has a strong correlation with the experimental quantities, like encapsulation efficiency and drug loading rate.