Temperature influence on the drug delivery performance of chitosan nanocomposites: A molecular dynamics simulation study

The classical cancer therapies such as chemotherapy are unfortunately ineffective due to their side effects, poor cellular uptake and drug resistance. Therefore, it is necessary to design and develop new drug delivery systems (DDSs) to decrease these drawbacks and enhance efficiencies [۱]. A DDS is a formulation, dosage form or device that can introduce a drug into the body to improve its efficacy and safety through controlling drug release rate/place [۲]. Chitosan (CS) is a natural cationic polysaccharide which is frequently used as drug delivery system due to its outstanding characteristics [۳]. Molecular dynamics (MD) simulations are broadly accomplished to understand physical phenomena occurring in complex membranes at the molecular level [۴]. In this work, molecular dynamics (MD) simulations were carried out on chitosan nanocomposite systems containing N-doped graphene (GN) or P-doped graphene (GP) nanoparticles for the delivery of ifosfamide (IF) anticancer drug in order to find the most suitable DDS. Moreover, the effect of temperature on the characteristics of these systems was investigated by running the MD simulations at four temperatures (۲۹۸.۱۵, ۳۰۸.۱۵, ۳۱۸.۱۵ and ۳۲۸.۱۵ K). The mean square displacement (MSD) and diffusion coefficient were enhanced by increasing the temperature. The surface area was enhanced by increasing the temperature from ۲۹۸.۱۵ to ۳۲۸.۱۵ K in the nanocomposites. It was recognized that at ۲۹۸.۱۵ K, the free volume (FV) was greater in the CS-GN-IF (۱۱۴۶۵.۶۸ Å۳) whereas it was decreased to ۱۱۲۹۶.۷۱ Å۳ in CS-GP-IF nanocomposite. Also, the FV was enhanced by raising the temperature from ۲۹۸.۱۵ to ۳۲۸.۱۵ K. A greater diffusion coefficient was measured at ۳۲۸.۱۵ K for the CS-GP-IF (۰.۰۶۱۳×۱۰–۵ cm۲/s) but the CS-GN-IF revealed a lower diffusion coefficient (۰.۰۵۶۵×۱۰–۵ cm۲/s) approving drug diffusion in the CS-GN-IF was more controlled leading to more efficient drug transport.