Theoretical aspects of interaction of the anticancer drug cytarabine with human serum albumin

Abstract

Despite diagnostic and therapeutic methods, cancer is a major cause of death worldwide. Since anticancer drugs affect both normal and cancer cells, targeted drug delivery systems can play a key role in reducing the destructive effects of anticancer drugs on normal cells. In this regard, the use of stimulus-sensitive polymers has increased in recent years. This study has attempted to investigate interaction of the anticancer drug cytarabine with a stimuli-sensitive polymer, human serum albumin (HSA), one of the most abundant protein in blood plasma, via computational methods at both body temperature and tumor temperature. For this purpose, molecular docking was performed using Molegro virtual Docker software to select the best ligand in terms of binding energy to simulate molecular dynamics. Then, molecular dynamics simulation was performed on human serum albumin with code (1Ao6) and cytarabine with code (AR3), using Gromacs software and the results were presented in the graphs. The simulations were performed at 310 K (normal cell temperature) and 313 K (cancer cell temperature) in 100 ns. Results showed drug release occurred at a temperature of 313 K. These findings demonstrated the sensitivity of human serum albumin to temperature.

Translational Challenges and Prospective Solutions in the Implementation of Biomimetic Delivery Systems

“…Such modifications and variability in drug release kinetics can influence drug efficacy, plasma levels, and safety [109,110]. Utilizing high-resolution techniques and computational modeling can provide structural insights and predict interaction behaviors in biological settings, helping in refining drug loading and streamlining the design process [111][112][113][114]. Scaling from the lab to the industrial level can impact product quality and characteristics in albumin-based systems, and the complexity of albumin modification challenges the reproducibility [102,115].…”